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Clinical Trial Results:
An Open-label, First-in-Human Study of the Safety, Tolerability, and Pharmacokinetics of VX-970/M6620 in Combination with Cytotoxic Chemotherapy in Participants With Advanced Solid Tumors

Summary
EudraCT number	2012-003126-25
Trial protocol	GB
Global end of trial date	11 Mar 2020

Results information
Results version number	v1(current)
This version publication date	21 Mar 2021
First version publication date	21 Mar 2021
Other versions

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

Top of page

Sponsor protocol code

MS201923-0001

ISRCTN number

US NCT number

NCT02157792

WHO universal trial number (UTN)

Sponsor organisation name

Merck KGaA, Darmstadt, Germany

Sponsor organisation address

Frankfurter Strasse 250, Darmstadt, Germany, 64293

Public contact

Communication Centre, Merck KGaA, Darmstadt, Germany, +49 6151725200, service@merckgroup.com

Scientific contact

Communication Center, Merck KGaA, Darmstadt, Germany, +49 6151725200, service@merckgroup.com

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Final

Date of interim/final analysis

11 Mar 2020

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

11 Mar 2020

Was the trial ended prematurely?

Main objective of the trial

The primary objective of this study is to evaluate the safety and tolerability of multiple ascending doses of intravenously administered M6620 in combination with gemcitabine, and in combination with cisplatin and gemcitabine, in subjects with advanced solid tumors.

Protection of trial subjects

Subject protection was ensured by following high medical and ethical standards in accordance with the principles laid down in the Declaration of Helsinki, and that are consistent with Good Clinical Practice and applicable regulations.

Background therapy

Evidence for comparator

Actual start date of recruitment

10 Dec 2012

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

United States: 79

Country: Number of subjects enrolled

United Kingdom: 118

Worldwide total number of subjects

197

EEA total number of subjects

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

134

From 65 to 84 years

85 years and over

Subject disposition

Top of page

Recruitment details

Screening details

First subject signed informed consent: 10 Dec 2012, Last subject last visit: 11 Mar 2020.

Period 1 title

Overall Study (overall period)

Is this the baseline period?

Yes

Allocation method

Not applicable

Blinding used

Not blinded

Are arms mutually exclusive

Yes

Part A1: M6620 18 mg/m^2 + Gemcitabine 875 mg/m^2

Arm description

Subjects received intravenous infusion of M6620 at a initial dose of 18 milligrams per square meter (mg/m^2) approximately for 24 hours later on Days 2 and 9 in combination with Gemcitabine at a dose of 875 mg/m^2 on Days 1 and 8 of a 21-day cycle up to 61 weeks.

Arm type

Experimental

Investigational medicinal product name

M6620

Investigational medicinal product code

M6620

Other name

Pharmaceutical forms

Concentrate for solution for injection/infusion

Routes of administration

Intravenous use

Dosage and administration details

Subjects received intravenous infusion of M6620 at a initial dose of 18 milligrams per square meter (mg/m^2) approximately for 24 hours later on Days 2 and 9 in combination with Gemcitabine.

Investigational medicinal product name

Gemcitabine

Investigational medicinal product code

Other name

Pharmaceutical forms

Concentrate for solution for injection/infusion

Routes of administration

Intravenous use

Dosage and administration details

Subjects received intravenous infusion of Gemcitabine at a dose of 875 mg/m^2 on Days 1 and 8 in combination with M6620.

Part A1: M6620 36 mg/m^2 + Gemcitabine 875 mg/m^2

Arm description

Subjects received intravenous infusion of M6620 at escalated dose of 36 mg/m^2 approximately for 24 hours later on Days 2 and 9 in combination with Gemcitabine at a dose of 875 mg/m^2 on Days 1 and 8 of a 21-day cycle up to 61 weeks.

Arm type

Experimental

Investigational medicinal product name

M6620

Investigational medicinal product code

M6620

Other name

Pharmaceutical forms

Concentrate for solution for injection/infusion

Routes of administration

Intravenous use

Dosage and administration details

Subjects received intravenous infusion of M6620 at escalated dose of 36 mg/m^2 approximately for 24 hours later on Days 2 and 9 in combination with Gemcitabine.

Investigational medicinal product name

Gemcitabine

Investigational medicinal product code

Other name

Pharmaceutical forms

Concentrate for solution for injection/infusion

Routes of administration

Intravenous use

Dosage and administration details

Subjects received intravenous infusion of Gemcitabine at a dose of 875 mg/m^2 on Days 1 and 8 in combination with M6620.

Part A1: M6620 60 mg/m^2 + Gemcitabine 875 mg/m^2

Arm description

Subjects received intravenous infusion of M6620 at escalated dose of 60 mg/m^2 approximately for 24 hours later on Days 2 and 9 in combination with Gemcitabine at a dose of 875 mg/m^2 on Days 1 and 8 of a 21-day cycle up to 61 weeks.

Arm type

Experimental

Investigational medicinal product name

M6620

Investigational medicinal product code

M6620

Other name

Pharmaceutical forms

Concentrate for solution for injection/infusion

Routes of administration

Intravenous use

Dosage and administration details

Subjects received intravenous infusion of M6620 at escalated dose of 60 mg/m^2 approximately for 24 hours later on Days 2 and 9 in combination with Gemcitabine.

Investigational medicinal product name

Gemcitabine

Investigational medicinal product code

Other name

Pharmaceutical forms

Concentrate for solution for injection/infusion

Routes of administration

Intravenous use

Dosage and administration details

Subjects received intravenous infusion of Gemcitabine at a dose of 875 mg/m^2 on Days 1 and 8 in combination with M6620.

Part A1: M6620 72 mg/m^2 + Gemcitabine 875 mg/m^2

Arm description

Subjects received intravenous infusion of M6620 at escalated dose of 72 mg/m^2 approximately for 24 hours later on Days 2 and 9 in combination with Gemcitabine at a dose of 875 mg/m^2 on Days 1 and 8 of a 21-day cycle up to 61 weeks.

Arm type

Experimental

Investigational medicinal product name

M6620

Investigational medicinal product code

M6620

Other name

Pharmaceutical forms

Concentrate for solution for injection/infusion

Routes of administration

Intravenous use

Dosage and administration details

Subjects received intravenous infusion of M6620 at escalated dose of 72 mg/m^2 approximately for 24 hours later on Days 2 and 9 in combination with Gemcitabine.

Investigational medicinal product name

Gemcitabine

Investigational medicinal product code

Other name

Pharmaceutical forms

Concentrate for solution for injection/infusion

Routes of administration

Intravenous use

Dosage and administration details

Subjects received intravenous infusion of Gemcitabineat at a dose of 875 mg/m^2 on Days 1 and 8 in combination with M6620.

Part A1: M6620 90 mg/m^2 + Gemcitabine 500 mg/m^2

Arm description

Subjects received intravenous infusion of M6620 at escalated dose of 90 mg/m^2 approximately for 24 hours later on Days 2 and 9 in combination with Gemcitabine at a dose of 500 mg/m^2 on Days 1 and 8 of a 21-day cycle up to 61 weeks.

Arm type

Experimental

Investigational medicinal product name

Gemcitabine

Investigational medicinal product code

Other name

Pharmaceutical forms

Concentrate for solution for injection/infusion

Routes of administration

Intravenous use

Dosage and administration details

Subjects received intravenous infusion of Gemcitabine at a dose of 500 mg/m^2 on Days 1 and 8 in combination with M6620.

Investigational medicinal product name

M6620

Investigational medicinal product code

M6620

Other name

Pharmaceutical forms

Concentrate for solution for injection/infusion

Routes of administration

Intravenous use

Dosage and administration details

Subjects received intravenous infusion of M6620 at escalated dose of 90 mg/m^2 approximately for 24 hours later on Days 2 and 9 in combination with Gemcitabine.

Part A1: M6620 140 mg/m^2 + Gemcitabine 500 mg/m^2

Arm description

Subjects received intravenous infusion of M6620 at escalated dose of 140 mg/m^2 approximately for 24 hours later on Days 2 and 9 in combination with Gemcitabine at a dose of 500 mg/m^2 on Days 1 and 8 of a 21-day cycle up to 61 weeks.

Arm type

Experimental

Investigational medicinal product name

Gemcitabine

Investigational medicinal product code

Other name

Pharmaceutical forms

Concentrate for solution for injection/infusion

Routes of administration

Intravenous use

Dosage and administration details

Subjects received intravenous infusion of Gemcitabine at dose of 500 mg/m^2 on Days 1 and 8 in combination with M6620.

Investigational medicinal product name

M6620

Investigational medicinal product code

M6620

Other name

Pharmaceutical forms

Concentrate for solution for injection/infusion

Routes of administration

Intravenous use

Dosage and administration details

Subjects received intravenous infusion of M6620 at escalated dose of 140 mg/m^2 approximately for 24 hours later on Days 2 and 9 in combination with Gemcitabine.

Part A1: M6620 210 mg/m^2 + Gemcitabine 500 mg/m^2

Arm description

Subjects received intravenous infusion of M6620 at escalated dose of 210 mg/m^2 approximately for 24 hours later on Days 2 and 9 in combination with Gemcitabine at a dose of 500 mg/m^2 on Days 1 and 8 of a 21-day cycle up to 61 weeks.

Arm type

Experimental

Investigational medicinal product name

M6620

Investigational medicinal product code

M6620

Other name

Pharmaceutical forms

Concentrate for solution for injection/infusion

Routes of administration

Intravenous use

Dosage and administration details

Subjects received intravenous infusion of M6620 at escalated dose of 210 mg/m^2 approximately for 24 hours later on Days 2 and 9 in combination with Gemcitabine.

Investigational medicinal product name

Gemcitabine

Investigational medicinal product code

Other name

Pharmaceutical forms

Concentrate for solution for injection/infusion

Routes of administration

Intravenous use

Dosage and administration details

Subjects received intravenous infusion of Gemcitabine at a dose of 500 mg/m^2 on Days 1 and 8 in combination with M6620.

Part A1: M6620 210 mg/m^2 + Gemcitabine 750 mg/m^2

Arm description

Subjects received intravenous infusion of M6620 at escalated dose of 210 mg/m^2 approximately for 24 hours later on Days 2 and 9 in combination with Gemcitabine at a dose of 750 mg/m^2 on Days 1 and 8 of a 21-day cycle up to 61 weeks.

Arm type

Experimental

Investigational medicinal product name

M6620

Investigational medicinal product code

M6620

Other name

Pharmaceutical forms

Concentrate for solution for injection/infusion

Routes of administration

Intravenous use

Dosage and administration details

Subjects received intravenous infusion of M6620 at escalated dose of 210 mg/m^2 approximately for 24 hours later on Days 2 and 9 in combination with Gemcitabine.

Investigational medicinal product name

Gemcitabine

Investigational medicinal product code

Other name

Pharmaceutical forms

Concentrate for solution for injection/infusion

Routes of administration

Intravenous use

Dosage and administration details

Subjects received intravenous infusion of Gemcitabine at a dose of 750 mg/m^2 on Days 1 and 8 in combination with M6620.

Part A1: M6620 210 mg/m^2 + Gemcitabine 875 mg/m^2

Arm description

Subjects received intravenous infusion of M6620 at escalated dose of 210 mg/m^2 approximately for 24 hours later on Days 2 and 9 in combination with Gemcitabine at a dose of 875 mg/m^2 on Days 1 and 8 of a 21-day cycle up to 61 weeks.

Arm type

Experimental

Investigational medicinal product name

Gemcitabine

Investigational medicinal product code

Other name

Pharmaceutical forms

Concentrate for solution for injection/infusion

Routes of administration

Intravenous use

Dosage and administration details

Subjects received intravenous infusion of Gemcitabine at a dose of 875 mg/m^2 on Days 1 and 8 in combination with M6620.

Investigational medicinal product name

M6620

Investigational medicinal product code

M6620

Other name

Pharmaceutical forms

Concentrate for solution for injection/infusion

Routes of administration

Intravenous use

Dosage and administration details

Subjects received intravenous infusion of M6620 at escalated dose of 210 mg/m^2 approximately for 24 hours later on Days 2 and 9 in combination with Gemcitabine.

Part A1: M6620 210 mg/m^2 + Gemcitabine 1000 mg/m^2

Arm description

Subjects received intravenous infusion of M6620 at escalated dose of 210 mg/m^2 approximately for 24 hours later on Days 2 and 9 in combination with Gemcitabine at a dose of 1000 mg/m^2 on Days 1 and 8 of a 21-day cycle up to 61 weeks.

Arm type

Experimental

Investigational medicinal product name

M6620

Investigational medicinal product code

M6620

Other name

Pharmaceutical forms

Concentrate for solution for injection/infusion

Routes of administration

Intravenous use

Dosage and administration details

Subjects received intravenous infusion of M6620 at escalated dose of 210 mg/m^2 approximately for 24 hours later on Days 2 and 9 in combination with Gemcitabine.

Investigational medicinal product name

Gemcitabine

Investigational medicinal product code

Other name

Pharmaceutical forms

Concentrate for solution for injection/infusion

Routes of administration

Intravenous use

Dosage and administration details

Subjects received intravenous infusion of Gemcitabine at a dose of 1000 mg/m^2 on Days 1 and 8 in combination with M6620.

Part A2: M6620 90 mg/m^2 + Gemcitabine + Cisplatin

Arm description

Subjects received intravenous infusion of M6620 at dose of 90 mg/m^2 approximately for 24 hours later on Days 2 and 9 in combination with Gemcitabine at a dose of 875 mg/m^2 on Days 1 and 8 and 60 mg/m^2 of Cisplatin on Day 1, of a 21-day cycle up to 41 weeks.

Arm type

Experimental

Investigational medicinal product name

M6620

Investigational medicinal product code

M6620

Other name

Pharmaceutical forms

Concentrate for solution for injection/infusion

Routes of administration

Intravenous use

Dosage and administration details

Subjects received intravenous infusion of M6620 at dose of 90 mg/m^2 approximately for 24 hours later on Days 2 and 9 in combination with Gemcitabine and Cisplatin.

Investigational medicinal product name

Gemcitabine

Investigational medicinal product code

Other name

Pharmaceutical forms

Concentrate for solution for injection/infusion

Routes of administration

Intravenous use

Dosage and administration details

Subjects received intravenous infusion of Gemcitabine at a dose of 875 mg/m^2 on Days 1 and 8 in combination with M6620 and Cisplatin.

Investigational medicinal product name

Cisplatin

Investigational medicinal product code

Other name

Pharmaceutical forms

Concentrate for solution for injection/infusion

Routes of administration

Intravenous use

Dosage and administration details

Subjects received intravenous infusion of Cisplatin at a dose 60 mg/m^2 on Day 1 in combination with M6620 and Gemcitabine.

Part A2: M6620 120 mg/m^2 + Gemcitabine + Cisplatin

Arm description

Subjects received intravenous infusion of M6620 at dose of 120 mg/m^2 approximately for 24 hours later on Days 2 and 9 in combination with Gemcitabine at a dose of 875 mg/m^2 on Days 1 and 8 and 60 mg/m^2 of Cisplatin on Day 1, of a 21-day cycle up to 41 weeks.

Arm type

Experimental

Investigational medicinal product name

M6620

Investigational medicinal product code

M6620

Other name

Pharmaceutical forms

Concentrate for solution for injection/infusion

Routes of administration

Intravenous use

Dosage and administration details

Subjects received intravenous infusion of M6620 at dose of 120 mg/m^2 approximately for 24 hours later on Days 2 and 9 in combination with Gemcitabine and Cisplatin.

Investigational medicinal product name

Cisplatin

Investigational medicinal product code

Other name

Pharmaceutical forms

Concentrate for solution for injection/infusion

Routes of administration

Intravenous use

Dosage and administration details

Subjects received intravenous infusion of Cisplatin at a dose of 60 mg/m^2 on Day 1 in combination with M6620 and Gemcitabine.

Investigational medicinal product name

Gemcitabine

Investigational medicinal product code

Other name

Pharmaceutical forms

Concentrate for solution for injection/infusion

Routes of administration

Intravenous use

Dosage and administration details

Subjects received intravenous infusion of Gemcitabine at a dose of 875 mg/m^2 on Days 1 and 8 n combination with M6620 and Cisplatin.

Part B1: M6620 140 mg/m^2

Arm description

Subjects received intravenous infusion of M6620 at dose of 140 mg/m^2 approximately for 24 hours later on Days 2 and 9 of a 21-day cycle up to 74 weeks.

Arm type

Experimental

Investigational medicinal product name

M6620

Investigational medicinal product code

Other name

Pharmaceutical forms

Concentrate for solution for injection/infusion

Routes of administration

Intravenous use

Dosage and administration details

Subjects received intravenous infusion of M6620 at dose of 140 mg/m^2 approximately for 24 hours later on Days 2 and 9.

Part B1: M6620 90 mg/m^2 + Cisplatin 40 mg/m^2

Arm description

Subjects received intravenous infusion of M6620 at dose of 90 mg/m^2 approximately for 24 hours later on Days 2 and 9 in combination with 40 mg/m^2 of Cisplatin on Day 1, of a 21-day cycle up to 74 weeks.

Arm type

Experimental

Investigational medicinal product name

M6620

Investigational medicinal product code

M6620

Other name

Pharmaceutical forms

Concentrate for solution for injection/infusion

Routes of administration

Intravenous use

Dosage and administration details

Subjects received intravenous infusion of M6620 at dose of 90 mg/m^2 approximately for 24 hours later on Days 2 and 9 in combination with Cisplatin.

Investigational medicinal product name

Cisplatin

Investigational medicinal product code

Other name

Pharmaceutical forms

Concentrate for solution for injection/infusion

Routes of administration

Intravenous use

Dosage and administration details

Subjects received intravenous infusion of Cisplatin at a dose of 40 mg/m^2 of on Day 1 in combination with M6620.

Part B1: M6620 140 mg/m^2 + Cisplatin 40 mg/m^2

Arm description

Subjects received intravenous infusion of M6620 at dose of 140mg/m^2 approximately for 24 hours later on Days 2 and 9 in combination with 40 mg/m^2 of Cisplatin on Day 1 of a 21-day cycle up to 74 weeks.

Arm type

Experimental

Investigational medicinal product name

M6620

Investigational medicinal product code

M6620

Other name

Pharmaceutical forms

Concentrate for solution for injection/infusion

Routes of administration

Intravenous use

Dosage and administration details

Subjects received intravenous infusion of M6620 at dose of 140mg/m^2 approximately for 24 hours later on Days 2 and 9 in combination with Cisplatin.

Investigational medicinal product name

Cisplatin

Investigational medicinal product code

Other name

Pharmaceutical forms

Concentrate for solution for injection/infusion

Routes of administration

Intravenous use

Dosage and administration details

Subjects received intravenous infusion of 40 mg/m^2 of Cisplatin on Day 1 in combination with M6620.

Part B1: M6620 210 mg/m^2 + Cisplatin 40 mg/m^2

Arm description

Subjects received intravenous infusion of M6620 at dose of 210 mg/m^2 approximately for 24 hours later on Days 2 and 9 in combination with 40 mg/m^2 of Cisplatin on Day 1 of a 21-day cycle up to 74 weeks.

Arm type

Experimental

Investigational medicinal product name

M6620

Investigational medicinal product code

Other name

Pharmaceutical forms

Concentrate for solution for injection/infusion

Routes of administration

Intravenous use

Dosage and administration details

Subjects received intravenous infusion of M6620 at dose of 210 mg/m^2 approximately for 24 hours later on Days 2 and 9 in combination with Cisplatin.

Investigational medicinal product name

Cisplatin

Investigational medicinal product code

Other name

Pharmaceutical forms

Concentrate for solution for injection/infusion

Routes of administration

Intravenous use

Dosage and administration details

Subjects received intravenous infusion of Cisplatin at a dose of 40 mg/m^2 of on Day 1 in combination with M6620.

Part B1: M6620 210 mg/m^2 + Cisplatin 60 mg/m^2

Arm description

Subjects received intravenous infusion of M6620 at dose of 210 mg/m^2 approximately for 24 hours later on Days 2 and 9 in combination with 60 mg/m^2 of Cisplatin on Day 1 of a 21-day cycle up to 74 weeks.

Arm type

Experimental

Investigational medicinal product name

M6620

Investigational medicinal product code

M6620

Other name

Pharmaceutical forms

Concentrate for solution for injection/infusion

Routes of administration

Intravenous use

Dosage and administration details

Subjects received intravenous infusion of M6620 at dose of 210 mg/m^2 approximately for 24 hours later on Days 2 and 9 in combination with Cisplatin.

Investigational medicinal product name

Cisplatin

Investigational medicinal product code

Other name

Pharmaceutical forms

Concentrate for solution for injection/infusion

Routes of administration

Intravenous use

Dosage and administration details

Subjects received intravenous infusion of Cisplatin at a dose of 60 mg/m^2 of on Day 1 in combination with M6620.

Part B1: M6620 140 mg/m^2 + Cisplatin 75 mg/m^2

Arm description

Subjects received intravenous infusion of M6620 at dose of 140 mg/m^2 approximately for 24 hours later on Days 2 and 9 in combination with 75 mg/m^2 of Cisplatin on Day 1 of a 21-day cycle up to 74 weeks.

Arm type

Experimental

Investigational medicinal product name

M6620

Investigational medicinal product code

M6620

Other name

Pharmaceutical forms

Concentrate for solution for injection/infusion

Routes of administration

Intravenous use

Dosage and administration details

Subjects received intravenous infusion of M6620 at dose of 140 mg/m^2 approximately for 24 hours later on Days 2 and 9 in combination with Cisplatin.

Investigational medicinal product name

Cisplatin

Investigational medicinal product code

Other name

Pharmaceutical forms

Concentrate for solution for injection/infusion

Routes of administration

Intravenous use

Dosage and administration details

Subjects received intravenous infusion of Cisplatin at a dose of 75 mg/m^2 on Day 1 in combination with M6620.

Part B1: M6620 210 mg/m^2 + Cisplatin 75 mg/m^2

Arm description

Subjects received intravenous infusion of M6620 at dose of 210 mg/m^2 approximately for 24 hours later on Days 2 and 9 in combination with 75 mg/m^2 of Cisplatin on Day 1 of a 21-day cycle up to 74 weeks.

Arm type

Experimental

Investigational medicinal product name

M6620

Investigational medicinal product code

M6620

Other name

Pharmaceutical forms

Concentrate for solution for injection/infusion

Routes of administration

Intravenous use

Dosage and administration details

Subjects received intravenous infusion of M6620 at dose of 210 mg/m^2 approximately for 24 hours later on Days 2 and 9 in combination with Cisplatin.

Investigational medicinal product name

Cisplatin

Investigational medicinal product code

Other name

Pharmaceutical forms

Concentrate for solution for injection/infusion

Routes of administration

Intravenous use

Dosage and administration details

Subjects received intravenous infusion of Cisplatin at a dose of 75 mg/m^2 of on Day 1 in combination with M6620.

Part B2: M6620 60 mg/m^2 + Irinotecan 180 mg/m^2

Arm description

Subjects received intravenous infusion of M6620 at a dose of 60 mg/m^2, in combination with irinotecan at a dose of 180 mg/m^2 (over 90 minutes) on Days 1 and 15 of a 28-day cycle up to 72 weeks.

Arm type

Experimental

Investigational medicinal product name

M6620

Investigational medicinal product code

M6620

Other name

Pharmaceutical forms

Concentrate for solution for injection/infusion

Routes of administration

Intravenous use

Dosage and administration details

Subjects received intravenous infusion of M6620 at a dose of 60 mg/m^2, in combination with irinotecan.

Investigational medicinal product name

Irinotecan

Investigational medicinal product code

Other name

Pharmaceutical forms

Concentrate for solution for injection/infusion

Routes of administration

Intravenous use

Dosage and administration details

Subjects received intravenous infusion of irinotecan at a dose of 180 mg/m^2 (over 90 minutes) on Days 1 and 15 in combination with M6620.

Part B2: M6620 90 mg/m^2 + Irinotecan 180 mg/m^2

Arm description

Subjects received intravenous infusion of M6620 at a dose of 90 mg/m^2, in combination with irinotecan at a dose of 180 mg/m^2 (over 90 minutes) on Days 1 and 15 of a 28-day cycle up to 72 weeks.

Arm type

Experimental

Investigational medicinal product name

M6620

Investigational medicinal product code

M6620

Other name

Pharmaceutical forms

Concentrate for solution for injection/infusion

Routes of administration

Intravenous use

Dosage and administration details

Subjects received intravenous infusion of M6620 at a dose of 90 mg/m^2, in combination with irinotecan.

Investigational medicinal product name

Irinotecan

Investigational medicinal product code

Other name

Pharmaceutical forms

Concentrate for solution for injection/infusion

Routes of administration

Intravenous use, Intravenous use

Dosage and administration details

Subjects received intravenous infusion of irinotecan at a dose of 180 mg/m^2 (over 90 minutes) on Days 1 and 15 in combination with M6620.

Part C1: M6620 210 mg/m^2 + Gemcitabine 1000 mg/m^2

Arm description

Subjects with advanced non-small cell lung cancer (NSCLC) received intravenous infusion of M6620 at a dose of 210 mg/m^2 on Days 2 and 9 in combination with Gemcitabine at a dose of 1000 mg/m^2 on Days 1 and 8 of a 21-day cycle up to 63 weeks.

Arm type

Experimental

Investigational medicinal product name

M6620

Investigational medicinal product code

M6620

Other name

Pharmaceutical forms

Concentrate for solution for injection/infusion

Routes of administration

Intravenous use

Dosage and administration details

Subjects with advanced non-small cell lung cancer (NSCLC) received intravenous infusion of M6620 at a dose of 210 mg/m^2 on Days 2 and 9 in combination with Gemcitabine.

Investigational medicinal product name

Gemcitabine

Investigational medicinal product code

Other name

Pharmaceutical forms

Concentrate for solution for injection/infusion

Routes of administration

Intravenous use

Dosage and administration details

Subjects with advanced non-small cell lung cancer (NSCLC) received intravenous infusion of Gemcitabine at a dose of 1000 mg/m^2 on Days 1 and 8 in combination with M6620.

Part C2: M6620 140 mg/m^2 + Cisplatin 75 mg/m^2

Arm description

Subjects with advanced triple negative breast cancer (TNBC) received intravenous infusion of M6620 at a dose of 140 mg/m^2 on Days 2 and 9 in combination with Cisplatin at a dose of 75 mg/m^2 on Day 1 of a 21-day cycle up to 137 weeks.

Arm type

Experimental

Investigational medicinal product name

M6620

Investigational medicinal product code

M6620

Other name

Pharmaceutical forms

Concentrate for solution for injection/infusion

Routes of administration

Intravenous use

Dosage and administration details

Subjects with advanced triple negative breast cancer (TNBC) received intravenous infusion of M6620 at a dose of 140 mg/m^2 on Days 2 and 9 in combination with Cisplatin.

Investigational medicinal product name

Cisplatin

Investigational medicinal product code

Other name

Pharmaceutical forms

Concentrate for solution for injection/infusion

Routes of administration

Intravenous use

Dosage and administration details

Subjects with advanced triple negative breast cancer (TNBC) received intravenous infusion of Cisplatin at a dose of 75 mg/m^2 on Day 1 in combination with M6620.

Part C3: M6620 140 mg/m^2 + Cisplatin 75 mg/m^2

Arm description

Subjects with platinum-resistant advanced small cell lung cancer (SCLC) received intravenous infusion of M6620 at a dose of 140 mg/m^2 on Days 2 and 9 in combination with Cisplatin at a dose of 75 mg/m^2 on Day 1 of a 21-day cycle up to 27 weeks.

Arm type

Experimental

Investigational medicinal product name

Cisplatin

Investigational medicinal product code

Other name

Pharmaceutical forms

Concentrate for solution for injection/infusion

Routes of administration

Intravenous use

Dosage and administration details

Subjects with platinum-resistant advanced small cell lung cancer (SCLC) received intravenous infusion of Cisplatin at a dose of 75 mg/m^2 on Day 1 in combination with M6620.

Investigational medicinal product name

M6620

Investigational medicinal product code

M6620

Other name

Pharmaceutical forms

Concentrate for solution for injection/infusion

Routes of administration

Intravenous use

Dosage and administration details

Subjects with platinum-resistant advanced small cell lung cancer (SCLC) received intravenous infusion of M6620 at a dose of 140 mg/m^2 on Days 2 and 9 in combination with Cisplatin.

Part C3: M6620 90 mg/m^2 + Carboplatin AUC 5 mg∙min/mL

Arm description

Subjects with platinum-resistant advanced SCLC received intravenous infusion of M6620 at a dose of 90 mg/m^2 on Days 2 and 9 in combination with carboplatin area under concentration-time curve (AUC) at a dose of 5 milligrams.minute per milliliter on Day 1 of a 21-day cycle up to 27 weeks.

Arm type

Experimental

Investigational medicinal product name

Carboplatin

Investigational medicinal product code

Other name

Pharmaceutical forms

Concentrate for solution for injection/infusion

Routes of administration

Intravenous use

Dosage and administration details

Subjects with platinum-resistant advanced SCLC received intravenous infusion of Carboplatin are under concentration-time curve (AUC) at a dose of 5 mg.min/mL on Day 1 in combination with M6620.

Investigational medicinal product name

M6620

Investigational medicinal product code

M6620

Other name

Pharmaceutical forms

Concentrate for solution for injection/infusion

Routes of administration

Intravenous use

Dosage and administration details

Subjects with platinum-resistant advanced SCLC received intravenous infusion of M6620 at a dose of 90 mg/m^2 on Days 2 and 9 in combination with Carboplatin.

Number of subjects in period 1	Part A1: M6620 18 mg/m^2 + Gemcitabine 875 mg/m^2	Part A1: M6620 36 mg/m^2 + Gemcitabine 875 mg/m^2	Part A1: M6620 60 mg/m^2 + Gemcitabine 875 mg/m^2	Part A1: M6620 72 mg/m^2 + Gemcitabine 875 mg/m^2	Part A1: M6620 90 mg/m^2 + Gemcitabine 500 mg/m^2	Part A1: M6620 140 mg/m^2 + Gemcitabine 500 mg/m^2	Part A1: M6620 210 mg/m^2 + Gemcitabine 500 mg/m^2	Part A1: M6620 210 mg/m^2 + Gemcitabine 750 mg/m^2	Part A1: M6620 210 mg/m^2 + Gemcitabine 875 mg/m^2	Part A1: M6620 210 mg/m^2 + Gemcitabine 1000 mg/m^2	Part A2: M6620 90 mg/m^2 + Gemcitabine + Cisplatin	Part A2: M6620 120 mg/m^2 + Gemcitabine + Cisplatin	Part B1: M6620 140 mg/m^2	Part B1: M6620 90 mg/m^2 + Cisplatin 40 mg/m^2	Part B1: M6620 140 mg/m^2 + Cisplatin 40 mg/m^2	Part B1: M6620 210 mg/m^2 + Cisplatin 40 mg/m^2	Part B1: M6620 210 mg/m^2 + Cisplatin 60 mg/m^2	Part B1: M6620 140 mg/m^2 + Cisplatin 75 mg/m^2	Part B1: M6620 210 mg/m^2 + Cisplatin 75 mg/m^2	Part B2: M6620 60 mg/m^2 + Irinotecan 180 mg/m^2	Part B2: M6620 90 mg/m^2 + Irinotecan 180 mg/m^2	Part C1: M6620 210 mg/m^2 + Gemcitabine 1000 mg/m^2	Part C2: M6620 140 mg/m^2 + Cisplatin 75 mg/m^2	Part C3: M6620 140 mg/m^2 + Cisplatin 75 mg/m^2	Part C3: M6620 90 mg/m^2 + Carboplatin AUC 5 mg∙min/mL
Started	3	3	4	7	6	8	3	3	7	6	6	2	1	3	3	4	10	7	3	5	3	38	47	2	13
Completed	3	3	4	7	6	8	3	3	7	6	6	2	1	3	3	4	10	7	3	5	3	38	47	2	13

Baseline characteristics

Top of page

Reporting group title

Part A1: M6620 18 mg/m^2 + Gemcitabine 875 mg/m^2

Reporting group description

Reporting group title

Part A1: M6620 36 mg/m^2 + Gemcitabine 875 mg/m^2

Reporting group description

Reporting group title

Part A1: M6620 60 mg/m^2 + Gemcitabine 875 mg/m^2

Reporting group description

Reporting group title

Part A1: M6620 72 mg/m^2 + Gemcitabine 875 mg/m^2

Reporting group description

Reporting group title

Part A1: M6620 90 mg/m^2 + Gemcitabine 500 mg/m^2

Reporting group description

Reporting group title

Part A1: M6620 140 mg/m^2 + Gemcitabine 500 mg/m^2

Reporting group description

Reporting group title

Part A1: M6620 210 mg/m^2 + Gemcitabine 500 mg/m^2

Reporting group description

Reporting group title

Part A1: M6620 210 mg/m^2 + Gemcitabine 750 mg/m^2

Reporting group description

Reporting group title

Part A1: M6620 210 mg/m^2 + Gemcitabine 875 mg/m^2

Reporting group description

Reporting group title

Part A1: M6620 210 mg/m^2 + Gemcitabine 1000 mg/m^2

Reporting group description

Reporting group title

Part A2: M6620 90 mg/m^2 + Gemcitabine + Cisplatin

Reporting group description

Reporting group title

Part A2: M6620 120 mg/m^2 + Gemcitabine + Cisplatin

Reporting group description

Reporting group title

Part B1: M6620 140 mg/m^2

Reporting group description

Subjects received intravenous infusion of M6620 at dose of 140 mg/m^2 approximately for 24 hours later on Days 2 and 9 of a 21-day cycle up to 74 weeks.

Reporting group title

Part B1: M6620 90 mg/m^2 + Cisplatin 40 mg/m^2

Reporting group description

Reporting group title

Part B1: M6620 140 mg/m^2 + Cisplatin 40 mg/m^2

Reporting group description

Reporting group title

Part B1: M6620 210 mg/m^2 + Cisplatin 40 mg/m^2

Reporting group description

Reporting group title

Part B1: M6620 210 mg/m^2 + Cisplatin 60 mg/m^2

Reporting group description

Reporting group title

Part B1: M6620 140 mg/m^2 + Cisplatin 75 mg/m^2

Reporting group description

Reporting group title

Part B1: M6620 210 mg/m^2 + Cisplatin 75 mg/m^2

Reporting group description

Reporting group title

Part B2: M6620 60 mg/m^2 + Irinotecan 180 mg/m^2

Reporting group description

Subjects received intravenous infusion of M6620 at a dose of 60 mg/m^2, in combination with irinotecan at a dose of 180 mg/m^2 (over 90 minutes) on Days 1 and 15 of a 28-day cycle up to 72 weeks.

Reporting group title

Part B2: M6620 90 mg/m^2 + Irinotecan 180 mg/m^2

Reporting group description

Subjects received intravenous infusion of M6620 at a dose of 90 mg/m^2, in combination with irinotecan at a dose of 180 mg/m^2 (over 90 minutes) on Days 1 and 15 of a 28-day cycle up to 72 weeks.

Reporting group title

Part C1: M6620 210 mg/m^2 + Gemcitabine 1000 mg/m^2

Reporting group description

Reporting group title

Part C2: M6620 140 mg/m^2 + Cisplatin 75 mg/m^2

Reporting group description

Reporting group title

Part C3: M6620 140 mg/m^2 + Cisplatin 75 mg/m^2

Reporting group description

Reporting group title

Part C3: M6620 90 mg/m^2 + Carboplatin AUC 5 mg∙min/mL

Reporting group description

Reporting group values	Part A1: M6620 18 mg/m^2 + Gemcitabine 875 mg/m^2	Part A1: M6620 36 mg/m^2 + Gemcitabine 875 mg/m^2	Part A1: M6620 60 mg/m^2 + Gemcitabine 875 mg/m^2	Part A1: M6620 72 mg/m^2 + Gemcitabine 875 mg/m^2	Part A1: M6620 90 mg/m^2 + Gemcitabine 500 mg/m^2	Part A1: M6620 140 mg/m^2 + Gemcitabine 500 mg/m^2	Part A1: M6620 210 mg/m^2 + Gemcitabine 500 mg/m^2	Part A1: M6620 210 mg/m^2 + Gemcitabine 750 mg/m^2	Part A1: M6620 210 mg/m^2 + Gemcitabine 875 mg/m^2	Part A1: M6620 210 mg/m^2 + Gemcitabine 1000 mg/m^2	Part A2: M6620 90 mg/m^2 + Gemcitabine + Cisplatin	Part A2: M6620 120 mg/m^2 + Gemcitabine + Cisplatin	Part B1: M6620 140 mg/m^2	Part B1: M6620 90 mg/m^2 + Cisplatin 40 mg/m^2	Part B1: M6620 140 mg/m^2 + Cisplatin 40 mg/m^2	Part B1: M6620 210 mg/m^2 + Cisplatin 40 mg/m^2	Part B1: M6620 210 mg/m^2 + Cisplatin 60 mg/m^2	Part B1: M6620 140 mg/m^2 + Cisplatin 75 mg/m^2	Part B1: M6620 210 mg/m^2 + Cisplatin 75 mg/m^2	Part B2: M6620 60 mg/m^2 + Irinotecan 180 mg/m^2	Part B2: M6620 90 mg/m^2 + Irinotecan 180 mg/m^2	Part C1: M6620 210 mg/m^2 + Gemcitabine 1000 mg/m^2	Part C2: M6620 140 mg/m^2 + Cisplatin 75 mg/m^2	Part C3: M6620 140 mg/m^2 + Cisplatin 75 mg/m^2	Part C3: M6620 90 mg/m^2 + Carboplatin AUC 5 mg∙min/mL	Total
Number of subjects	3	3	4	7	6	8	3	3	7	6	6	2	1	3	3	4	10	7	3	5	3	38	47	2	13	197
Age Categorical
Units: subjects
<=18 years	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Between 18 and 65 years	3	2	3	5	3	6	3	2	3	3	4	2	1	2	0	3	4	5	1	4	2	22	43	2	6	134
>=65 years	0	1	1	2	3	2	0	1	4	3	2	0	0	1	3	1	6	2	2	1	1	16	4	0	7	63
Sex: Female, Male
Units: subjects
Female	2	0	1	4	3	2	2	2	3	3	3	1	1	2	1	1	5	6	1	3	1	18	47	2	8	122
Male	1	3	3	3	3	6	1	1	4	3	3	1	0	1	2	3	5	1	2	2	2	20	0	0	5	75
Race (NIH/OMB)
Units: Subjects
American Indian or Alaska Native	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Asian	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	1	1	0	0	0	0	1	1	0	0	5
Native Hawaiian or Other Pacific Islander	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Black or African American	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	1	0	0	0	0	0	2	0	2	6
White	3	2	4	7	6	8	3	3	7	6	6	2	1	3	2	3	8	7	3	3	3	34	41	2	11	178
More than one race	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	1	0	0	0	2
Unknown or Not Reported	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	2	3	0	0	6
Ethnicity (NIH/OMB)
Units: Subjects
Hispanic or Latino	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	5	3	3	4	0	0	15
Not Hispanic or Latino	3	3	4	7	5	8	3	3	7	6	6	2	1	3	3	4	10	7	3	0	0	32	41	1	13	175
Unknown or Not Reported	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	3	2	1	0	7

End points

Top of page

Reporting group title

Part A1: M6620 18 mg/m^2 + Gemcitabine 875 mg/m^2

Reporting group description

Reporting group title

Part A1: M6620 36 mg/m^2 + Gemcitabine 875 mg/m^2

Reporting group description

Reporting group title

Part A1: M6620 60 mg/m^2 + Gemcitabine 875 mg/m^2

Reporting group description

Reporting group title

Part A1: M6620 72 mg/m^2 + Gemcitabine 875 mg/m^2

Reporting group description

Reporting group title

Part A1: M6620 90 mg/m^2 + Gemcitabine 500 mg/m^2

Reporting group description

Reporting group title

Part A1: M6620 140 mg/m^2 + Gemcitabine 500 mg/m^2

Reporting group description

Reporting group title

Part A1: M6620 210 mg/m^2 + Gemcitabine 500 mg/m^2

Reporting group description

Reporting group title

Part A1: M6620 210 mg/m^2 + Gemcitabine 750 mg/m^2

Reporting group description

Reporting group title

Part A1: M6620 210 mg/m^2 + Gemcitabine 875 mg/m^2

Reporting group description

Reporting group title

Part A1: M6620 210 mg/m^2 + Gemcitabine 1000 mg/m^2

Reporting group description

Reporting group title

Part A2: M6620 90 mg/m^2 + Gemcitabine + Cisplatin

Reporting group description

Reporting group title

Part A2: M6620 120 mg/m^2 + Gemcitabine + Cisplatin

Reporting group description

Reporting group title

Part B1: M6620 140 mg/m^2

Reporting group description

Subjects received intravenous infusion of M6620 at dose of 140 mg/m^2 approximately for 24 hours later on Days 2 and 9 of a 21-day cycle up to 74 weeks.

Reporting group title

Part B1: M6620 90 mg/m^2 + Cisplatin 40 mg/m^2

Reporting group description

Reporting group title

Part B1: M6620 140 mg/m^2 + Cisplatin 40 mg/m^2

Reporting group description

Reporting group title

Part B1: M6620 210 mg/m^2 + Cisplatin 40 mg/m^2

Reporting group description

Reporting group title

Part B1: M6620 210 mg/m^2 + Cisplatin 60 mg/m^2

Reporting group description

Reporting group title

Part B1: M6620 140 mg/m^2 + Cisplatin 75 mg/m^2

Reporting group description

Reporting group title

Part B1: M6620 210 mg/m^2 + Cisplatin 75 mg/m^2

Reporting group description

Reporting group title

Part B2: M6620 60 mg/m^2 + Irinotecan 180 mg/m^2

Reporting group description

Subjects received intravenous infusion of M6620 at a dose of 60 mg/m^2, in combination with irinotecan at a dose of 180 mg/m^2 (over 90 minutes) on Days 1 and 15 of a 28-day cycle up to 72 weeks.

Reporting group title

Part B2: M6620 90 mg/m^2 + Irinotecan 180 mg/m^2

Reporting group description

Subjects received intravenous infusion of M6620 at a dose of 90 mg/m^2, in combination with irinotecan at a dose of 180 mg/m^2 (over 90 minutes) on Days 1 and 15 of a 28-day cycle up to 72 weeks.

Reporting group title

Part C1: M6620 210 mg/m^2 + Gemcitabine 1000 mg/m^2

Reporting group description

Reporting group title

Part C2: M6620 140 mg/m^2 + Cisplatin 75 mg/m^2

Reporting group description

Reporting group title

Part C3: M6620 140 mg/m^2 + Cisplatin 75 mg/m^2

Reporting group description

Reporting group title

Part C3: M6620 90 mg/m^2 + Carboplatin AUC 5 mg∙min/mL

Reporting group description

Subject analysis set title

Part A1: All Subjects

Subject analysis set type

Safety analysis

Subject analysis set description

Subjects who received M6620 at a dose of 18, 36, 60, 72, 90, 140 or 210 mg/m^2 approximately for 24 hours later on Days 2 and 9 in combination with Gemicitabine at a dose of 875, 500, 750 or 1000 mg/m^2 on Days 1 and 8 of a 21-day cycle up to 61 weeks.

Subject analysis set title

Part A2: All Subjects

Subject analysis set type

Safety analysis

Subject analysis set description

Subjects who received M6620 at a dose of 90 or120 mg/m^2 in combination with Gemcitabine at a dose of 875 mg/m^2 on Days 1 and 8 and 60 mg/m^2 of Cisplatin on Day 1 of a 21-day cycle up to 41 weeks.

Subject analysis set title

Parts B1: All Subjects

Subject analysis set type

Safety analysis

Subject analysis set description

Subjects who received intravenous infusion of M6620 at dose of 140, 90 or 210 mg/m^2 approximately for 24 hours later on Days 2 and 9 in combination with Cisplatin at a dose 40, 60 or 75 mg/m^2 on Day 1 of a 21-day cycle up to 74 weeks.

Subject analysis set title

Part B2: All Subjects

Subject analysis set type

Safety analysis

Subject analysis set description

Subjects who received intravenous infusion of M6620 at a dose of 60 or 90 mg/m^2 in combination with irinotecan at a dose of 180 mg/m^2 (over 90 minutes) on Days 1 and 15 of a 28-day cycle up to 72 weeks.

Subject analysis set title

Part A1: M6620 120 mg/m^2 and Gemcitabine

Subject analysis set type

Full analysis

Subject analysis set description

Subjects who received intravenous infusion of M6620 at escalated dose of 120 mg/m^2 approximately for 24 hours later on Days 2 and 9 in combination with Gemcitabine at a dose of 500, 750, 875 or 1000 mg/m^2 on Days 1 and 8 of a 21-day cycle up to 61 weeks.

Subject analysis set title

Part A1: M6620 210 mg/m^2 and Gemcitabine

Subject analysis set type

Full analysis

Subject analysis set description

Subjects who received intravenous infusion of M6620 at escalated dose of 210 mg/m^2 approximately for 24 hours later on Days 2 and 9 in combination with Gemcitabine at a dose of 750, 875 or 1000 mg/m^2 on Days 1 and 8 of a 21-day cycle up to 61 weeks.

Subject analysis set title

Part B1: M6620 140 mg/m^2 and Cisplatin

Subject analysis set type

Full analysis

Subject analysis set description

Subjects who received intravenous infusion of M6620 at dose of 140mg/m^2 approximately for 24 hours later on Days 2 and 9 in combination with Cisplatin at a dose of 40 or 75 mg/m^2 on Day 1 of a 21-day cycle up to 74 weeks.

Subject analysis set title

Part B1: M6620 210 mg/m^2 and Cisplatin

Subject analysis set type

Full analysis

Subject analysis set description

Subjects who received intravenous infusion of M6620 at dose of 210 mg/m^2 approximately for 24 hours later on Days 2 and 9 in combination with Cisplatin at a dose of 40, 60 or 75 mg/m^2 on Day 1 of a 21-day cycle up to 74 weeks.

Primary: Parts A1, A2, B1: Number of Subjects with Treatment-Emergent Adverse Events (TEAEs)

Top of page

End point title

Parts A1, A2, B1: Number of Subjects with Treatment-Emergent Adverse Events (TEAEs) ^[1] ^[2]

End point description

Adverse event (AE) was defined as any untoward medical occurrence in a subject, which does not necessarily have causal relationship with treatment. A serious AE was defined as an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. TEAEs were those events with onset dates occurring during the on-treatment period for the first time, or if the worsening of an event was during the on-treatment period. TEAEs included both serious TEAEs and non-serious TEAEs. Safety set included all subjects who received at least 1 dose of study drug.

End point type

Primary

End point timeframe

Time from first dose of study treatment up to 4.6 years

Notes
[1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Only descriptive summary statistics was planned for this endpoint.
[2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: In this endpoint, we have reported data for Part A1, Part A2 and Part B1 arms only. For Part B2, Part C1, C2 and C3 arms we have created separate endpoints due to change in the time frame.

End point values	Part A1: M6620 18 mg/m^2 + Gemcitabine 875 mg/m^2	Part A1: M6620 36 mg/m^2 + Gemcitabine 875 mg/m^2	Part A1: M6620 60 mg/m^2 + Gemcitabine 875 mg/m^2	Part A1: M6620 72 mg/m^2 + Gemcitabine 875 mg/m^2	Part A1: M6620 90 mg/m^2 + Gemcitabine 500 mg/m^2	Part A1: M6620 140 mg/m^2 + Gemcitabine 500 mg/m^2	Part A1: M6620 210 mg/m^2 + Gemcitabine 500 mg/m^2	Part A1: M6620 210 mg/m^2 + Gemcitabine 750 mg/m^2	Part A1: M6620 210 mg/m^2 + Gemcitabine 875 mg/m^2	Part A1: M6620 210 mg/m^2 + Gemcitabine 1000 mg/m^2	Part A2: M6620 90 mg/m^2 + Gemcitabine + Cisplatin	Part A2: M6620 120 mg/m^2 + Gemcitabine + Cisplatin	Part B1: M6620 140 mg/m^2	Part B1: M6620 90 mg/m^2 + Cisplatin 40 mg/m^2	Part B1: M6620 140 mg/m^2 + Cisplatin 40 mg/m^2	Part B1: M6620 210 mg/m^2 + Cisplatin 40 mg/m^2	Part B1: M6620 210 mg/m^2 + Cisplatin 60 mg/m^2	Part B1: M6620 140 mg/m^2 + Cisplatin 75 mg/m^2	Part B1: M6620 210 mg/m^2 + Cisplatin 75 mg/m^2
Number of subjects analysed	3	3	4	7	6	8	3	3	7	6	6	2	1	3	3	4	10	7	3
Units: subjects	3	3	4	6	6	8	3	3	7	6	6	2	1	3	3	3	10	7	3

No statistical analyses for this end point

Primary: Parts A1, A2, B1: Number of Subjects with Clinically Significant Changes From Baseline in Laboratory Parameters

Top of page

End point title

Parts A1, A2, B1: Number of Subjects with Clinically Significant Changes From Baseline in Laboratory Parameters ^[3] ^[4]

End point description

Laboratory investigation included hematology, biochemistry, urinalysis and coagulation. Clinical significance was determined by the investigator. The number of subjects with clinically significant changes from baseline in laboratory parameters were reported. Safety set included all subjects who received at least 1 dose of study drug.

End point type

Primary

End point timeframe

Time from first dose of study treatment up to 4.6 years

Notes
[3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Only descriptive summary statistics was planned for this endpoint.
[4] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: In this endpoint, we have reported data for Part A1, Part A2 and Part B1 arms only. For Part B2, Part C1, C2 and C3 arms we have created separate endpoints due to change in the time frame.

End point values	Part A1: M6620 18 mg/m^2 + Gemcitabine 875 mg/m^2	Part A1: M6620 36 mg/m^2 + Gemcitabine 875 mg/m^2	Part A1: M6620 60 mg/m^2 + Gemcitabine 875 mg/m^2	Part A1: M6620 72 mg/m^2 + Gemcitabine 875 mg/m^2	Part A1: M6620 90 mg/m^2 + Gemcitabine 500 mg/m^2	Part A1: M6620 140 mg/m^2 + Gemcitabine 500 mg/m^2	Part A1: M6620 210 mg/m^2 + Gemcitabine 500 mg/m^2	Part A1: M6620 210 mg/m^2 + Gemcitabine 750 mg/m^2	Part A1: M6620 210 mg/m^2 + Gemcitabine 875 mg/m^2	Part A1: M6620 210 mg/m^2 + Gemcitabine 1000 mg/m^2	Part A2: M6620 90 mg/m^2 + Gemcitabine + Cisplatin	Part A2: M6620 120 mg/m^2 + Gemcitabine + Cisplatin	Part B1: M6620 140 mg/m^2	Part B1: M6620 90 mg/m^2 + Cisplatin 40 mg/m^2	Part B1: M6620 140 mg/m^2 + Cisplatin 40 mg/m^2	Part B1: M6620 210 mg/m^2 + Cisplatin 40 mg/m^2	Part B1: M6620 210 mg/m^2 + Cisplatin 60 mg/m^2	Part B1: M6620 140 mg/m^2 + Cisplatin 75 mg/m^2	Part B1: M6620 210 mg/m^2 + Cisplatin 75 mg/m^2
Number of subjects analysed	3	3	4	7	6	8	3	3	7	6	6	2	1	3	3	4	10	7	3
Units: subjects	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0

No statistical analyses for this end point

Primary: Parts A1, A2, B1: Number of Subjects with Clinically Significant Changes From Baseline in Vital Signs

Top of page

End point title

Parts A1, A2, B1: Number of Subjects with Clinically Significant Changes From Baseline in Vital Signs ^[5] ^[6]

End point description

Vital signs included body temperature, systolic and diastolic blood pressure, pulse rate and respiratory rate. Clinical significance was determined by the investigator. The number of subjects with clinically significant changes fom baseline in vital signs were reported. Safety set included all subjects who received at least 1 dose of study drug.

End point type

Primary

End point timeframe

Time from first dose of study treatment up to 4.6 years

Notes
[5] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Only descriptive summary statistics was planned for this endpoint.
[6] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: In this endpoint, we have reported data for Part A1, Part A2 and Part B1 arms only. For Part B2, Part C1, C2 and C3 arms we have created separate endpoints due to change in the time frame.

End point values	Part A1: M6620 18 mg/m^2 + Gemcitabine 875 mg/m^2	Part A1: M6620 36 mg/m^2 + Gemcitabine 875 mg/m^2	Part A1: M6620 60 mg/m^2 + Gemcitabine 875 mg/m^2	Part A1: M6620 72 mg/m^2 + Gemcitabine 875 mg/m^2	Part A1: M6620 90 mg/m^2 + Gemcitabine 500 mg/m^2	Part A1: M6620 140 mg/m^2 + Gemcitabine 500 mg/m^2	Part A1: M6620 210 mg/m^2 + Gemcitabine 500 mg/m^2	Part A1: M6620 210 mg/m^2 + Gemcitabine 750 mg/m^2	Part A1: M6620 210 mg/m^2 + Gemcitabine 875 mg/m^2	Part A1: M6620 210 mg/m^2 + Gemcitabine 1000 mg/m^2	Part A2: M6620 90 mg/m^2 + Gemcitabine + Cisplatin	Part A2: M6620 120 mg/m^2 + Gemcitabine + Cisplatin	Part B1: M6620 140 mg/m^2	Part B1: M6620 90 mg/m^2 + Cisplatin 40 mg/m^2	Part B1: M6620 140 mg/m^2 + Cisplatin 40 mg/m^2	Part B1: M6620 210 mg/m^2 + Cisplatin 40 mg/m^2	Part B1: M6620 210 mg/m^2 + Cisplatin 60 mg/m^2	Part B1: M6620 140 mg/m^2 + Cisplatin 75 mg/m^2	Part B1: M6620 210 mg/m^2 + Cisplatin 75 mg/m^2
Number of subjects analysed	3	3	4	7	6	8	3	3	7	6	6	2	1	3	3	4	10	7	3
Units: subjects	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0

No statistical analyses for this end point

Primary: Parts A1, A2, B1: Number of Subjects with Clinically Significant Changes From Baseline in 12-Lead Electrocardiograms (ECGs) Findings

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End point title

Parts A1, A2, B1: Number of Subjects with Clinically Significant Changes From Baseline in 12-Lead Electrocardiograms (ECGs) Findings ^[7] ^[8]

End point description

12-lead ECG recordings included rhythm, heart rate (as measured by RR interval), PR interval, QRS duration, and QT interval. 12-lead ECG recordings were obtained after the subjects have rested for at least 5 minutes in supine position. Clinical significance was determined by the investigator. The number of subjects with clinically significant changes from baseline in 12-lead ECG findings were reported. Safety set included all subjects who received at least 1 dose of study drug.

End point type

Primary

End point timeframe

Time from first dose of study treatment up to 4.6 years

Notes
[7] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Only descriptive summary statistics was planned for this endpoint.
[8] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: In this endpoint, we have reported data for Part A1, Part A2 and Part B1 arms only. For Part B2, Part C1, C2 and C3 arms we have created separate endpoints due to change in the time frame.

End point values	Part A1: M6620 18 mg/m^2 + Gemcitabine 875 mg/m^2	Part A1: M6620 36 mg/m^2 + Gemcitabine 875 mg/m^2	Part A1: M6620 60 mg/m^2 + Gemcitabine 875 mg/m^2	Part A1: M6620 72 mg/m^2 + Gemcitabine 875 mg/m^2	Part A1: M6620 90 mg/m^2 + Gemcitabine 500 mg/m^2	Part A1: M6620 140 mg/m^2 + Gemcitabine 500 mg/m^2	Part A1: M6620 210 mg/m^2 + Gemcitabine 500 mg/m^2	Part A1: M6620 210 mg/m^2 + Gemcitabine 750 mg/m^2	Part A1: M6620 210 mg/m^2 + Gemcitabine 875 mg/m^2	Part A1: M6620 210 mg/m^2 + Gemcitabine 1000 mg/m^2	Part A2: M6620 90 mg/m^2 + Gemcitabine + Cisplatin	Part A2: M6620 120 mg/m^2 + Gemcitabine + Cisplatin	Part B1: M6620 140 mg/m^2	Part B1: M6620 90 mg/m^2 + Cisplatin 40 mg/m^2	Part B1: M6620 140 mg/m^2 + Cisplatin 40 mg/m^2	Part B1: M6620 210 mg/m^2 + Cisplatin 40 mg/m^2	Part B1: M6620 210 mg/m^2 + Cisplatin 60 mg/m^2	Part B1: M6620 140 mg/m^2 + Cisplatin 75 mg/m^2	Part B1: M6620 210 mg/m^2 + Cisplatin 75 mg/m^2
Number of subjects analysed	3	3	4	7	6	8	3	3	7	6	6	2	1	3	3	4	10	7	3
Units: subjects	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0

No statistical analyses for this end point

Primary: Part B2: Number of Subjects with Treatment-Emergent Adverse Events (TEAEs)

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End point title

Part B2: Number of Subjects with Treatment-Emergent Adverse Events (TEAEs) ^[9] ^[10]

End point description

Adverse event (AE) was defined as any untoward medical occurrence in a subject, which does not necessarily have causal relationship with treatment. A serious AE was defined as an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. TEAEs were those events with onset dates occurring during the on-treatment period for the first time, or if the worsening of an event was during the on-treatment period. TEAEs included both serious TEAEs and non-serious TEAEs. Safety Analysis Set (SAF) included all screening analysis set subjects who received at least 1 administration of study drug (irinotecan or M6620).

End point type

Primary

End point timeframe

Time from first dose of study treatment up to 1.6 years

Notes
[9] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Only descriptive summary statistics was planned for this endpoint.
[10] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: In this endpoint, we have reported data for Part B2 arms only. For Parts A1, A2, B1, C1, C2 and C3 arms we have created separate endpoints due to change in the time frame.

End point values	Part B2: M6620 60 mg/m^2 + Irinotecan 180 mg/m^2	Part B2: M6620 90 mg/m^2 + Irinotecan 180 mg/m^2
Number of subjects analysed	5	3
Units: subjects	5	3

No statistical analyses for this end point

Primary: Part B2: Number of Subjects with Clinically Significant Changes from Baseline in Laboratory Parameters

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End point title

Part B2: Number of Subjects with Clinically Significant Changes from Baseline in Laboratory Parameters ^[11] ^[12]

End point description

Laboratory investigation included hematology, biochemistry, urinalysis and coagulation. Clinical significance was determined by the investigator. The number of subjects with clinically significant changes from baseline in laboratory parameters were reported. SAF included all screening analysis set subjects who received at least 1 administration of study drug (irinotecan or M6620).

End point type

Primary

End point timeframe

Time from first dose of study treatment up to 1.6 years

Notes
[11] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Only descriptive summary statistics was planned for this endpoint.
[12] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: In this endpoint, we have reported data for Part B2 arms only. For Parts A1, A2, B1, C1, C2 and C3 arms we have created separate endpoints due to change in the time frame.

End point values	Part B2: M6620 60 mg/m^2 + Irinotecan 180 mg/m^2	Part B2: M6620 90 mg/m^2 + Irinotecan 180 mg/m^2
Number of subjects analysed	5	3
Units: subjects	0	0

No statistical analyses for this end point

Primary: Part B2: Number of Subjects with Clinically Significant Changes from Baseline in Vital Signs

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End point title

Part B2: Number of Subjects with Clinically Significant Changes from Baseline in Vital Signs ^[13] ^[14]

End point description

Vital signs included body temperature, systolic and diastolic blood pressure, pulse rate and respiratory rate. Clinical significance was determined by the investigator. The number of subjects with clinically significant changes from baseline in vital signs were reported. SAF included all screening analysis set subjects who received at least 1 administration of study drug (irinotecan or M6620).

End point type

Primary

End point timeframe

Time from first dose of study treatment up to 1.6 years

Notes
[13] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Only descriptive summary statistics was planned for this endpoint.
[14] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: In this endpoint, we have reported data for Part B2 arms only. For Parts A1, A2, B1, C1, C2 and C3 arms we have created separate endpoints due to change in the time frame.

End point values	Part B2: M6620 60 mg/m^2 + Irinotecan 180 mg/m^2	Part B2: M6620 90 mg/m^2 + Irinotecan 180 mg/m^2
Number of subjects analysed	5	3
Units: subjects	0	0

No statistical analyses for this end point

Primary: Part B2: Number of Subjects with Clinically Significant Changes from Baseline in 12-Lead Electrocardiograms (ECGs) Findings

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End point title

Part B2: Number of Subjects with Clinically Significant Changes from Baseline in 12-Lead Electrocardiograms (ECGs) Findings ^[15] ^[16]

End point description

12-lead ECG recordings included rhythm, heart rate (as measured by RR interval), PR interval, QRS duration, and QT interval. 12-lead ECG recordings were obtained after the subjects have rested for at least 5 minutes in supine position. Clinical significance was determined by the investigator. The number of subjects with clinically significant changes from baseline in 12-lead ECG findings were reported. SAF included all screening analysis set subjects who received at least 1 administration of study drug (irinotecan or M6620).

End point type

Primary

End point timeframe

Time from first dose of study treatment up to 1.6 years

Notes
[15] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Only descriptive summary statistics was planned for this endpoint.
[16] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: In this endpoint, we have reported data for Part B2 arms only. For Parts A1, A2, B1, C1, C2 and C3 arms we have created separate endpoints due to change in the time frame.

End point values	Part B2: M6620 60 mg/m^2 + Irinotecan 180 mg/m^2	Part B2: M6620 90 mg/m^2 + Irinotecan 180 mg/m^2
Number of subjects analysed	5	3
Units: subjects	0	0

No statistical analyses for this end point

Primary: Parts C1, C2, C3: Number of Subjects with Treatment-Emergent Adverse Events (TEAEs)

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End point title

Parts C1, C2, C3: Number of Subjects with Treatment-Emergent Adverse Events (TEAEs) ^[17] ^[18]

End point description

Adverse event (AE) was defined as any untoward medical occurrence in a subject, which does not necessarily have causal relationship with treatment. A serious AE was defined as an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. TEAEs were those events with onset dates occurring during the on-treatment period for the first time, or if the worsening of an event was during the on-treatment period. TEAEs included both serious TEAEs and non-serious TEAEs. SAF: all enrolled subjects (irrespective of biomarker status) who received at least 1 dose of study drug (M6620, gemcitabine, cisplatin, or carboplatin; actual amount > 0 mg and/or the duration of infusion > 0 minutes).

End point type

Primary

End point timeframe

Time from first dose of study treatment up to 4.3 years

Notes
[17] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Only descriptive summary statistics was planned for this endpoint.
[18] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: In this endpoint, we have reported data for Part C1, C2 and C3 arms only. For Parts A1, A2, B1 and B2 arms we have created separate endpoints due to change in the time frame.

End point values	Part C1: M6620 210 mg/m^2 + Gemcitabine 1000 mg/m^2	Part C2: M6620 140 mg/m^2 + Cisplatin 75 mg/m^2	Part C3: M6620 140 mg/m^2 + Cisplatin 75 mg/m^2	Part C3: M6620 90 mg/m^2 + Carboplatin AUC 5 mg∙min/mL
Number of subjects analysed	38	47	2	13
Units: subjects	38	47	2	13

No statistical analyses for this end point

Primary: Parts C1, C2, C3: Number of Subjects with Clinically Significant Changes from Baseline in Laboratory Parameters

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End point title

Parts C1, C2, C3: Number of Subjects with Clinically Significant Changes from Baseline in Laboratory Parameters ^[19] ^[20]

End point description

Laboratory investigation included hematology, biochemistry, urinalysis and coagulation. Clinical significance was determined by the investigator. The number of subjects with clinically significant changes from baseline in laboratory parameters were reported. SAF: all enrolled subjects (irrespective of biomarker status) who received at least 1 dose of study drug (M6620, gemcitabine, cisplatin, or carboplatin; actual amount > 0 mg and/or the duration of infusion > 0 minutes).

End point type

Primary

End point timeframe

Time from first dose of study treatment up to 4.3 years

Notes
[19] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Only descriptive summary statistics was planned for this endpoint.
[20] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: In this endpoint, we have reported data for Parts C1, C2 and C3 arms only. For Part A1, A2, B1 and B2 arms we have created separate endpoints due to change in the time frame.

End point values	Part C1: M6620 210 mg/m^2 + Gemcitabine 1000 mg/m^2	Part C2: M6620 140 mg/m^2 + Cisplatin 75 mg/m^2	Part C3: M6620 140 mg/m^2 + Cisplatin 75 mg/m^2	Part C3: M6620 90 mg/m^2 + Carboplatin AUC 5 mg∙min/mL
Number of subjects analysed	38	47	2	13
Units: subjects	0	0	0	0

No statistical analyses for this end point

Primary: Parts C1, C2, C3: Number of Subjects with Clinically Significant Changes from Baseline in Vital Signs

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End point title

Parts C1, C2, C3: Number of Subjects with Clinically Significant Changes from Baseline in Vital Signs ^[21] ^[22]

End point description

Vital signs included body temperature, systolic and diastolic blood pressure, pulse rate and respiratory rate. Clinical significance was determined by the investigator. The number of subjects with clinically significant changes from baseline in vital signs were reported. SAF: all enrolled subjects (irrespective of biomarker status) who received at least 1 dose of study drug (M6620, gemcitabine, cisplatin, or carboplatin; actual amount > 0 mg and/or the duration of infusion > 0 minutes).

End point type

Primary

End point timeframe

Time from first dose of study treatment up to 4.3 years

Notes
[21] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Only descriptive summary statistics was planned for this endpoint.
[22] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: In this endpoint, we have reported data for Parts C1, C2 and C3 arms only. For Part A1, A2, B1 and B2 arms we have created separate endpoints due to change in the time frame.

End point values	Part C1: M6620 210 mg/m^2 + Gemcitabine 1000 mg/m^2	Part C2: M6620 140 mg/m^2 + Cisplatin 75 mg/m^2	Part C3: M6620 140 mg/m^2 + Cisplatin 75 mg/m^2	Part C3: M6620 90 mg/m^2 + Carboplatin AUC 5 mg∙min/mL
Number of subjects analysed	38	47	2	13
Units: subjects	0	0	0	0

No statistical analyses for this end point

Primary: Parts C1, C2 and C3: Number of Subjects with Clinically Significant Changes from Baseline in 12-Lead Electrocardiograms (ECGs) Findings

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End point title

Parts C1, C2 and C3: Number of Subjects with Clinically Significant Changes from Baseline in 12-Lead Electrocardiograms (ECGs) Findings ^[23] ^[24]

End point description

12-lead ECG recordings included rhythm, heart rate (as measured by RR interval), PR interval, QRS duration, and QT interval. 12-lead ECG recordings were obtained after the subjects have rested for at least 5 minutes in supine position. Clinical significance was determined by the investigator. The number of subjects with clinically significant changes from baseline in 12-lead ECG findings were reported. SAF: all enrolled subjects (irrespective of biomarker status) who received at least 1 dose of study drug (M6620, gemcitabine, cisplatin, or carboplatin; actual amount > 0 mg and/or the duration of infusion > 0 minutes).

End point type

Primary

End point timeframe

Time from first dose of study treatment up to 4.3 years

Notes
[23] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Only descriptive summary statistics was planned for this endpoint.
[24] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: In this endpoint, we have reported data for Parts C1, C2 and C3 arms only. For Part A1, A2, B1 and B2 arms we have created separate endpoints due to change in the time frame.

End point values	Part C1: M6620 210 mg/m^2 + Gemcitabine 1000 mg/m^2	Part C2: M6620 140 mg/m^2 + Cisplatin 75 mg/m^2	Part C3: M6620 140 mg/m^2 + Cisplatin 75 mg/m^2	Part C3: M6620 90 mg/m^2 + Carboplatin AUC 5 mg∙min/mL
Number of subjects analysed	38	47	2	13
Units: subjects	0	0	0	0

No statistical analyses for this end point

Primary: Parts C1 and C3: Percentage of Subjects with Objective Response (OR)

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End point title

Parts C1 and C3: Percentage of Subjects with Objective Response (OR) ^[25] ^[26]

End point description

OR was defined as the percentage of subjects who had achieved partial response (PR) or complete response (CR) as the best overall response according to according to Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST v1.1). CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the sum of the longest diameter (SLD) of all lesions. Modified Full Analysis Set (mFAS): all enrolled subjects who satisfy both of following conditions:1) Received at least 1 dose of study drug (M6620, gemcitabine, cisplatin/carboplatin with the actual amount greater than [>] 0 mg and/the duration of infusion > 0 minutes; 2) Had a Baseline scan of disease assessment (Computed tomography [CT]/Magnetic resonance imaging [MRI]) with a measurable target lesion (sum of diameters of all target lesions > 0 millimeter [mm]).

End point type

Primary

End point timeframe

Time from first dose of study treatment up to 4.3 years

Notes
[25] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Only descriptive summary statistics was planned for this endpoint.
[26] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: In this endpoint, we have reported data for Parts C1 and C3 arms only. For Part A1, A2, B1, B2 and C2 arms we have created separate endpoints.

End point values	Part C1: M6620 210 mg/m^2 + Gemcitabine 1000 mg/m^2	Part C3: M6620 140 mg/m^2 + Cisplatin 75 mg/m^2	Part C3: M6620 90 mg/m^2 + Carboplatin AUC 5 mg∙min/mL
Number of subjects analysed	38	2	13
Units: percentage of subjects
number (confidence interval 90%)	10.5 (3.7 to 22.5)	0.0 (0.0 to 77.6)	0.0 (0.0 to 20.6)

No statistical analyses for this end point

Primary: Part C2: Percentage of Subjects with Objective Response (OR) in Part C2 (TNBC) Who are Basaloid Subtype and BRCA1/BRCA2 Germline wild-type

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End point title

Part C2: Percentage of Subjects with Objective Response (OR) in Part C2 (TNBC) Who are Basaloid Subtype and BRCA1/BRCA2 Germline wild-type ^[27] ^[28]

End point description

End point type

Primary

End point timeframe

Time from first dose of study treatment up to 4.3 years

Notes
[27] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Only descriptive summary statistics was planned for this endpoint.
[28] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: In this endpoint, the data was planned to be reported for subjects with Basaloid subtype (BRCA1/BRCA2) in Part B2 only.

End point values	Part C2: M6620 140 mg/m^2 + Cisplatin 75 mg/m^2
Number of subjects analysed	47
Units: percentage of subjects
number (confidence interval 90%)	22.6 (11.1 to 38.3)

No statistical analyses for this end point

Secondary: Parts A1 and A2: Maximum Tolerated Dose (MTD) of M6620

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End point title

Parts A1 and A2: Maximum Tolerated Dose (MTD) of M6620

End point description

Part A1: MTD of M6620 with gemcitabine was defined as the highest dose of M6620 tolerated in combination with a gemcitabine. Part A2: MTD of M6620 was defined as the highest dose of M6620 tolerated in combination with a cisplatin and gemcitabine. Dose limiting toxicity (DLT) evaluable set was defined as all subjects enrolled in Part A or Part B1 who either had a DLT before Day 21 in Cycle 1; or received all doses of gemcitabine and/or cisplatin, as applicable, and all doses of M6620 during Cycle.

End point type

Secondary

End point timeframe

Up to Cycle 1 Day 21 (each cycle is 21 days)

End point values	Part A1: All Subjects	Part A2: All Subjects
Number of subjects analysed	50	8
Units: mg/m^2
number (not applicable)	210	90

No statistical analyses for this end point

Secondary: Part A1: Maximum Observed Plasma Concentration (Cmax) of M6620

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End point title

Part A1: Maximum Observed Plasma Concentration (Cmax) of M6620 ^[29]

End point description

Cmax was obtained directly from the concentration versus time curve. Full Analysis Set (FAS) included all subjects who had baseline scan and received at least 1 dose of study drug and had at least once post-baseline disease assessment (including staging CT scan or nonstaging CT scan indicating disease progression, end of treatment due to progression disease [PD] or death).

End point type

Secondary

End point timeframe

Pre-infusion, 0.5, 1, 2, 3 and 7 hours after end of infusion (EOI) on Cycle 1 Day 2 (each cycle is of 21 days)

Notes
[29] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: In this endpoint, we have reported data for Part A1 arms only. For Parts A2, B1, B2, C1, C2 and C3 arms we have created separate endpoints.

End point values	Part A1: M6620 90 mg/m^2 + Gemcitabine 500 mg/m^2	Part A1: M6620 120 mg/m^2 and Gemcitabine	Part A1: M6620 210 mg/m^2 and Gemcitabine
Number of subjects analysed	6	2	16
Units: nanogram per milliliter (ng/mL)
geometric mean (geometric coefficient of variation)	571 ( 34 )	486 ( 28 )	899 ( 41 )

No statistical analyses for this end point

Secondary: Part A1: Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity (AUC0-inf) of M6620

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End point title

Part A1: Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity (AUC0-inf) of M6620 ^[30]

End point description

AUC0-inf was calculated by combining AUC0-t and AUCextra. AUC extra represents an extrapolated value obtained by Clast/ lambda z, where Clast is the calculated plasma concentration at the last sampling time point at which the measured plasma concentration is at or above the Lower Limit of quantification (LLOQ) and lambda z is the apparent terminal rate constant determined by log-linear regression analysis of the measured plasma concentrations of the terminal log-linear phase. FAS included all subjecst who had baseline scan, received at least 1 dose of study drug and had at least once post-baseline disease assessment (including staging CT scan or nonstaging CT scan indicating disease progression, end of treatment due to progression disease [PD] or death).

End point type

Secondary

End point timeframe

Pre-infusion, 0.5, 1, 2, 3 and 7 hours after end of infusion (EOI) on Cycle 1 Day 2 (each cycle is of 21 days)

Notes
[30] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: In this endpoint, we have reported data for Part A1 arms only. For Parts A2, B1, B2, C1, C2 and C3 arms we have created separate endpoints.

End point values	Part A1: M6620 90 mg/m^2 + Gemcitabine 500 mg/m^2	Part A1: M6620 120 mg/m^2 and Gemcitabine	Part A1: M6620 210 mg/m^2 and Gemcitabine
Number of subjects analysed	6	2	16
Units: nanogramhour per milliliter (nghr/mL)
geometric mean (geometric coefficient of variation)	3100 ( 39 )	4160 ( 3.5 )	6690 ( 31 )

No statistical analyses for this end point

Secondary: Part A1: Apparent Volume of Distribution at Steady-state (Vss) of M6620

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End point title

Part A1: Apparent Volume of Distribution at Steady-state (Vss) of M6620 ^[31]

End point description

Vss was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. Steady state volume of distribution (Vss) was the apparent volume of distribution at steady-state. FAS included all subjects who had baseline scan, received at least 1 dose of study drug and had at least once post-baseline disease assessment (including staging CT scan or nonstaging CT scan indicating disease progression, end of treatment due to progression disease [PD] or death).

End point type

Secondary

End point timeframe

Pre-infusion, 0.5, 1, 2, 3 and 7 hours after end of infusion (EOI) on Cycle 1 Day 2 (each cycle is of 21 days)

Notes
[31] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: In this endpoint, we have reported data for Part A1 arms only. For Parts A2, B1, B2, C1, C2 and C3 arms we have created separate endpoints.

End point values	Part A1: M6620 90 mg/m^2 + Gemcitabine 500 mg/m^2	Part A1: M6620 120 mg/m^2 and Gemcitabine	Part A1: M6620 210 mg/m^2 and Gemcitabine
Number of subjects analysed	6	2	16
Units: liters
geometric mean (geometric coefficient of variation)	983 ( 35 )	1240 ( 14 )	1250 ( 22 )

No statistical analyses for this end point

Secondary: Part A1: Apparent Total Body Clearance (CL) of M6620

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End point title

Part A1: Apparent Total Body Clearance (CL) of M6620 ^[32]

End point description

CL was a measure of the rate at which M6620 was metabolized or eliminated by normal biological processes. Clearance obtained after oral dose was influenced by the fraction of the dose absorbed. FAS included all subjects who had baseline scan, received at least 1 dose of study drug and had at least once post-baseline disease assessment (including staging CT scan or nonstaging CT scan indicating disease progression, end of treatment due to PD or death).

End point type

Secondary

End point timeframe

Pre-infusion, 0.5, 1, 2, 3 and 7 hours after end of infusion (EOI) on Cycle 1 Day 2 (each cycle is of 21 days)

Notes
[32] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: In this endpoint, we have reported data for Part A1 arms only. For Parts A2, B1, B2, C1, C2 and C3 arms we have created separate endpoints.

End point values	Part A1: M6620 90 mg/m^2 + Gemcitabine 500 mg/m^2	Part A1: M6620 120 mg/m^2 and Gemcitabine	Part A1: M6620 210 mg/m^2 and Gemcitabine
Number of subjects analysed	6	2	16
Units: liter per hour
geometric mean (geometric coefficient of variation)	64.2 ( 45 )	55.5 ( 1 )	62.3 ( 31 )

No statistical analyses for this end point

Secondary: Part A1: Apparent Terminal Half-Life (t1/2) of M6620

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End point title

Part A1: Apparent Terminal Half-Life (t1/2) of M6620 ^[33]

End point description

Apparent terminal half-life was defined as the time required for the plasma concentration of drug to decrease 50 percent in the final stage of its elimination. FAS included all subjects who had baseline scan, received at least 1 dose of study drug and had at least once post-baseline disease assessment (including staging CT scan or nonstaging CT scan indicating disease progression, end of treatment due to PD or death).

End point type

Secondary

End point timeframe

Pre-infusion, 0.5, 1, 2, 3 and 7 hours after end of infusion (EOI) on Cycle 1 Day 2 (each cycle is of 21 days)

Notes
[33] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: In this endpoint, we have reported data for Part A1 arms only. For Parts A2, B1, B2, C1, C2 and C3 arms we have created separate endpoints.

End point values	Part A1: M6620 90 mg/m^2 + Gemcitabine 500 mg/m^2	Part A1: M6620 120 mg/m^2 and Gemcitabine	Part A1: M6620 210 mg/m^2 and Gemcitabine
Number of subjects analysed	6	2	16
Units: hours
geometric mean (geometric coefficient of variation)	14.2 ( 27 )	17.6 ( 14 )	17.3 ( 24 )

No statistical analyses for this end point

Secondary: Parts A1, A2 and B1: Percentage of Subjects with Objective Tumor Response (OR) as Evaluated by Response Criteria Evaluation in Solid Tumors (RECIST) 1.1

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End point title

Parts A1, A2 and B1: Percentage of Subjects with Objective Tumor Response (OR) as Evaluated by Response Criteria Evaluation in Solid Tumors (RECIST) 1.1 ^[34]

End point description

Objective tumor response was defined as having a complete response (CR) or a partial response (PR). Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. FAS included all subjecst who had baseline scan, received at least 1 dose of study drug and had at least once post-baseline disease assessment (including staging CT scan or nonstaging CT scan indicating disease progression, end of treatment due to PD or death). Here, "number of subjects analyzed" signifies those subjects who were evaluable for this endpoint. Here, '99999' signifies that data is not available as none of the subjects showed CR or PR at specified time point.

End point type

Secondary

End point timeframe

Time from first dose of study treatment up to 4.6 years

Notes
[34] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: In this endpoint, we have reported data for Part A1, Part A2 and Part B1 arms only. For Part B2, Part C1, C2 and C3 arms we have created separate endpoints due to change in the time frame.

Part A1: M6620 18 mg/m^2 + Gemcitabine 875 mg/m^2

Part A1: M6620 36 mg/m^2 + Gemcitabine 875 mg/m^2

Part A1: M6620 60 mg/m^2 + Gemcitabine 875 mg/m^2

Part A1: M6620 72 mg/m^2 + Gemcitabine 875 mg/m^2

Part A1: M6620 90 mg/m^2 + Gemcitabine 500 mg/m^2

Part A1: M6620 140 mg/m^2 + Gemcitabine 500 mg/m^2

Part A1: M6620 210 mg/m^2 + Gemcitabine 500 mg/m^2

Part A1: M6620 210 mg/m^2 + Gemcitabine 750 mg/m^2

Part A1: M6620 210 mg/m^2 + Gemcitabine 875 mg/m^2

Part A1: M6620 210 mg/m^2 + Gemcitabine 1000 mg/m^2

Part A2: M6620 90 mg/m^2 + Gemcitabine + Cisplatin

Part A2: M6620 120 mg/m^2 + Gemcitabine + Cisplatin

Part B1: M6620 90 mg/m^2 + Cisplatin 40 mg/m^2

Part B1: M6620 140 mg/m^2 + Cisplatin 40 mg/m^2

Part B1: M6620 210 mg/m^2 + Cisplatin 40 mg/m^2

Part B1: M6620 210 mg/m^2 + Cisplatin 60 mg/m^2

Part B1: M6620 140 mg/m^2 + Cisplatin 75 mg/m^2

Part B1: M6620 210 mg/m^2 + Cisplatin 75 mg/m^2

Number of subjects analysed

Units: percentage of subjects

number (confidence interval 90%)

99999 (99999 to 99999)

33.3 (1.7 to 86.5)

99999 (99999 to 99999)

28.6 (5.3 to 65.9)

99999 (99999 to 99999)

33.3 (1.7 to 86.5)

99999 (99999 to 99999)

16.7 (0.9 to 58.2)

99999 (99999 to 99999)

25.0 (1.3 to 75.1)

99999 (99999 to 99999)

75.0 (24.9 to 98.7)

99999 (99999 to 99999)

No statistical analyses for this end point

Secondary: Part B1: Maximum Tolerated Dose (MTD) of M6620

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End point title

Part B1: Maximum Tolerated Dose (MTD) of M6620

End point description

M6620 MTD was defined as the highest dose of M6620 tolerated in combination with a cisplatin. DLT evaluable set was defined as all subjects enrolled in Part A or Part B1 who either had a DLT before Day 21 in Cycle 1; or received all doses of gemcitabine and/or cisplatin, as applicable, and all doses of M6620 during Cycle.

End point type

Secondary

End point timeframe

Up to Cycle 1 Day 21 (each cycle is 21 days)

End point values	Parts B1: All Subjects
Number of subjects analysed	31
Units: mg/m^2
number (not applicable)	140

No statistical analyses for this end point

Secondary: Part B2: Maximum Tolerated Dose (MTD) of M6620

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End point title

Part B2: Maximum Tolerated Dose (MTD) of M6620

End point description

The MTD for M6620 in combination with irinotecan was defined as the highest dose for a given schedule at which there were no more than 1 of 6 subjects with DLT. DLT Evaluable Set: all SAF subjects who either experienced a DLT before the end of Cycle 1 and received any amount of M6620 or received at least 80% of the cumulative planned dose of irinotecan and at least 80% of the cumulative planned dose of M6620 during Cycle 1 and completed Cycle 1, i.e., had a study visit on Day 28 or later

End point type

Secondary

End point timeframe

Up to Cycle 1 Day 28 (each cycle is of 28 days)

End point values	Part B2: All Subjects
Number of subjects analysed	0 ^[35]
Units: mg/m^2
number (not applicable)

Notes
[35] - MTD was not determined as Part B2 was discontinued after observing toxicities at first dose level.

No statistical analyses for this end point

Secondary: Part B1: Maximum Observed Plasma Concentration (Cmax) of M6620

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End point title

Part B1: Maximum Observed Plasma Concentration (Cmax) of M6620 ^[36]

End point description

Cmax was obtained directly from the concentration versus time curve. FAS included all subjects who had baseline scan, received at least 1 dose of study drug and had at least once post-baseline disease assessment (including staging CT scan or nonstaging CT scan indicating disease progression, end of treatment due to PD or death).

End point type

Secondary

End point timeframe

Pre-infusion, 0.5, 1, 2, 3 and 7 hours after EOI on Cycle 1 Day 2 (each cycle is 21 days)

Notes
[36] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: In this endpoint, we have reported data for Part B1 arms only. For Parts A1, A2, B2, C1, C2 and C3 arms we have created separate endpoints.

End point values	Part B1: M6620 90 mg/m^2 + Cisplatin 40 mg/m^2	Part B1: M6620 140 mg/m^2 and Cisplatin	Part B1: M6620 210 mg/m^2 and Cisplatin
Number of subjects analysed	2	8	17
Units: nanogram per milliliter (ng/mL)
geometric mean (geometric coefficient of variation)	458 ( 13 )	854 ( 63 )	1230 ( 43 )

No statistical analyses for this end point

Secondary: Part B1: Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity (AUC0-inf) of M6620

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End point title

Part B1: Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity (AUC0-inf) of M6620 ^[37]

End point description

AUC0-inf was calculated by combining AUC0-t and AUCextra. AUC extra represents an extrapolated value obtained by Clast/ lambda z, where Clast is the calculated plasma concentration at the last sampling time point at which the measured plasma concentration is at or above the Lower Limit of quantification (LLOQ) and lambda z is the apparent terminal rate constant determined by log-linear regression analysis of the measured plasma concentrations of the terminal log-linear phase. FAS included all subjects who had baseline scan, received at least 1 dose of study drug and had at least once post-baseline disease assessment (including staging CT scan or nonstaging CT scan indicating disease progression, end of treatment due to PD or death).

End point type

Secondary

End point timeframe

Pre-infusion, 0.5, 1, 2, 3 and 7 hours after EOI on Cycle 1 Day 2 (each cycle is 21 days)

Notes
[37] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: In this endpoint, we have reported data for Part B1 arms only. For Parts A1, A2, B2, C1, C2 and C3 arms we have created separate endpoint.

End point values	Part B1: M6620 90 mg/m^2 + Cisplatin 40 mg/m^2	Part B1: M6620 140 mg/m^2 and Cisplatin	Part B1: M6620 210 mg/m^2 and Cisplatin
Number of subjects analysed	2	8	17
Units: nanogramhour per milliliter (nghr/mL)
geometric mean (geometric coefficient of variation)	2820 ( 15 )	4870 ( 28 )	6740 ( 32 )

No statistical analyses for this end point

Secondary: Part B1: Apparent Volume of Distribution at Steady-state (Vss) of M6620

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End point title

Part B1: Apparent Volume of Distribution at Steady-state (Vss) of M6620 ^[38]

End point description

End point type

Secondary

End point timeframe

Pre-infusion, 0.5, 1, 2, 3 and 7 hours after EOI on Cycle 1 Day 2 (each cycle is 21 days)

Notes
[38] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: In this endpoint, we have reported data for Part B1 arms only. For Parts A1, A2, B2, C1, C2 and C3 arms we have created separate endpoints.

End point values	Part B1: M6620 90 mg/m^2 + Cisplatin 40 mg/m^2	Part B1: M6620 140 mg/m^2 and Cisplatin	Part B1: M6620 210 mg/m^2 and Cisplatin
Number of subjects analysed	2	8	17
Units: liters
geometric mean (geometric coefficient of variation)	1260 ( 38 )	1060 ( 36 )	1270 ( 28 )

No statistical analyses for this end point

Secondary: Part B1: Apparent Total Body Clearance (CL) of M6620

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End point title

Part B1: Apparent Total Body Clearance (CL) of M6620 ^[39]

End point description

End point type

Secondary

End point timeframe

Pre-infusion, 0.5, 1, 2, 3 and 7 hours after EOI on Cycle 1 Day 2 (each cycle is 21 days)

Notes
[39] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: In this endpoint, we have reported data for Part B1 arms only. For Parts A1, A2, B2, C1, C2 and C3 arms we have created separate endpoints.

End point values	Part B1: M6620 90 mg/m^2 + Cisplatin 40 mg/m^2	Part B1: M6620 140 mg/m^2 and Cisplatin	Part B1: M6620 210 mg/m^2 and Cisplatin
Number of subjects analysed	2	8	17
Units: liters
geometric mean (geometric coefficient of variation)	61.1 ( 20 )	54.7 ( 31 )	62.6 ( 32 )

No statistical analyses for this end point

Secondary: Part B1: Apparent Terminal Half-Life (t1/2) of M6620

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End point title

Part B1: Apparent Terminal Half-Life (t1/2) of M6620 ^[40]

End point description

End point type

Secondary

End point timeframe

Pre-infusion, 0.5, 1, 2, 3 and 7 hours after EOI on Cycle 1 Day 2 (each cycle is 21 days)

Notes
[40] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: In this endpoint, we have reported data for Part B1 arms only. For Parts A1, A2, B2, C1, C2 and C3 arms we have created separate endpoints.

End point values	Part B1: M6620 90 mg/m^2 + Cisplatin 40 mg/m^2	Part B1: M6620 140 mg/m^2 and Cisplatin	Part B1: M6620 210 mg/m^2 and Cisplatin
Number of subjects analysed	2	8	17
Units: hours
geometric mean (geometric coefficient of variation)	17.0 ( 26 )	17.5 ( 34 )	17.3 ( 17 )

No statistical analyses for this end point

Secondary: Part B2: Maximum Observed Plasma Concentration (Cmax) of M6620

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End point title

Part B2: Maximum Observed Plasma Concentration (Cmax) of M6620 ^[41]

End point description

Cmax was obtained directly from the concentration versus time curve. Pharmacokinetic Analysis Set (PAS) included all SAF subjects who received at least 1 administration of study drug (irinotecan or M6620) and provided at least 1 measurable postdose concentration of M6620 or irinotecan or its metabolites.

End point type

Secondary

End point timeframe

Cycle 1 Days 1 through 3: pre-infusion, and 1, 2, 3, 7, 23 and 47 hours after EOI; Cycle 1 Day 15 and Cycle 2 Day 1 at pre-infusion, and EOI to 2 hours after EOI (each cycle is of 28 days)

Notes
[41] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: In this endpoint, we have reported data for Part B2 arms only. For Parts A1, A2, B1, C1, C2 and C3 arms we have created separate endpoints.

End point values	Part B2: M6620 60 mg/m^2 + Irinotecan 180 mg/m^2	Part B2: M6620 90 mg/m^2 + Irinotecan 180 mg/m^2
Number of subjects analysed	0 ^[42]	0 ^[43]
Units: ng/mL
geometric mean (geometric coefficient of variation)	( )	( )

Notes
[42] - As per revised planned analysis, pharmacokinetic parameters for Part B2 was not assessed.
[43] - As per revised planned analysis, pharmacokinetic parameters for Part B2 was not assessed.

No statistical analyses for this end point

Secondary: Part B2: Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity (AUC0-inf) of M6620

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End point title

Part B2: Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity (AUC0-inf) of M6620 ^[44]

End point description

AUC0-inf was calculated by combining AUC0-t and AUCextra. AUC extra represents an extrapolated value obtained by Clast/ lambda z, where Clast is the calculated plasma concentration at the last sampling time point at which the measured plasma concentration is at or above the Lower Limit of quantification (LLOQ) and lambda z is the apparent terminal rate constant determined by log-linear regression analysis of the measured plasma concentrations of the terminal log-linear phase. PAS included all SAF subjects who received at least 1 administration of study drug (irinotecan or M6620) and provided at least 1 measurable postdose concentration of M6620 or irinotecan or its metabolites.

End point type

Secondary

End point timeframe

Cycle 1 Days 1 through 3: pre-infusion, and 1, 2, 3, 7, 23 and 47 hours after EOI; Cycle 1 Day 15 and Cycle 2 Day 1 at pre-infusion, and EOI to 2 hours after EOI (each cycle is of 28 days)

Notes
[44] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: In this endpoint, we have reported data for Part B2 arms only. For Parts A1, A2, B1, C1, C2 and C3 arms we have created separate endpoints.

End point values	Part B2: M6620 60 mg/m^2 + Irinotecan 180 mg/m^2	Part B2: M6620 90 mg/m^2 + Irinotecan 180 mg/m^2
Number of subjects analysed	0 ^[45]	0 ^[46]
Units: ng*hr/mL
geometric mean (geometric coefficient of variation)	( )	( )

Notes
[45] - As per revised planned analysis, pharmacokinetic parameters for Part B2 was not assessed.
[46] - As per revised planned analysis, pharmacokinetic parameters for Part B2 was not assessed.

No statistical analyses for this end point

Secondary: Part B2: Volume of Distribution at Steady-state (Vss) of M6620

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End point title

Part B2: Volume of Distribution at Steady-state (Vss) of M6620 ^[47]

End point description

Vss was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. Steady state volume of distribution (Vss) was the apparent volume of distribution at steady-state. PAS included all SAF subjects who received at least 1 administration of study drug (irinotecan or M6620) and provided at least 1 measurable postdose concentration of M6620 or irinotecan or its metabolites

End point type

Secondary

End point timeframe

Cycle 1 Days 1 through 3: pre-infusion, and 1, 2, 3, 7, 23 and 47 hours after EOI; Cycle 1 Day 15 and Cycle 2 Day 1 at pre-infusion, and EOI to 2 hours after EOI (each cycle is of 28 days)

Notes
[47] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: In this endpoint, we have reported data for Part B2 arms only. For Parts A1, A2, B1, C1, C2 and C3 arms we have created separate endpoints.

End point values	Part B2: M6620 60 mg/m^2 + Irinotecan 180 mg/m^2	Part B2: M6620 90 mg/m^2 + Irinotecan 180 mg/m^2
Number of subjects analysed	0 ^[48]	0 ^[49]
Units: liters
geometric mean (geometric coefficient of variation)	( )	( )

Notes
[48] - As per revised planned analysis, pharmacokinetic parameters for Part B2 was not assessed.
[49] - As per revised planned analysis, pharmacokinetic parameters for Part B2 was not assessed.

No statistical analyses for this end point

Secondary: Part B2: Apparent Total Body Clearance (CL) of M6620

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End point title

Part B2: Apparent Total Body Clearance (CL) of M6620 ^[50]

End point description

CL was a measure of the rate at which M6620 was metabolized or eliminated by normal biological processes. Clearance obtained after oral dose was influenced by the fraction of the dose absorbed. PAS included all SAF subjects who received at least 1 administration of study drug (irinotecan or M6620) and provided at least 1 measurable postdose concentration of M6620 or irinotecan or its metabolites.

End point type

Secondary

End point timeframe

Cycle 1 Days 1 through 3: pre-infusion, and 1, 2, 3, 7, 23 and 47 hours after EOI; Cycle 1 Day 15 and Cycle 2 Day 1 at pre-infusion, and EOI to 2 hours after EOI (each cycle is of 28 days)

Notes
[50] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: In this endpoint, we have reported data for Part B2 arms only. For Parts A1, A2, B1, C1, C2 and C3 arms we have created separate endpoints.

End point values	Part B2: M6620 60 mg/m^2 + Irinotecan 180 mg/m^2	Part B2: M6620 90 mg/m^2 + Irinotecan 180 mg/m^2
Number of subjects analysed	0 ^[51]	0 ^[52]
Units: liter per hour
geometric mean (geometric coefficient of variation)	( )	( )

Notes
[51] - As per revised planned analysis, pharmacokinetic parameters for Part B2 was not assessed.
[52] - As per revised planned analysis, pharmacokinetic parameters for Part B2 was not assessed.

No statistical analyses for this end point

Secondary: Part B2: Apparent Terminal Half-Life (t1/2) of M6620

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End point title

Part B2: Apparent Terminal Half-Life (t1/2) of M6620 ^[53]

End point description

Apparent terminal half-life was defined as the time required for the plasma concentration of drug to decrease 50 percent in the final stage of its elimination. PAS included all SAF subjects who received at least 1 administration of study drug (irinotecan or M6620) and provided at least 1 measurable postdose concentration of M6620 or irinotecan or its metabolites.

End point type

Secondary

End point timeframe

Cycle 1 Days 1 through 3: pre-infusion, and 1, 2, 3, 7, 23 and 47 hours after EOI; Cycle 1 Day 15 and Cycle 2 Day 1 at pre-infusion, and EOI to 2 hours after EOI (each cycle is of 28 days)

Notes
[53] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: In this endpoint, we have reported data for Part B2 arms only. For Parts A1, A2, B1, C1, C2 and C3 arms we have created separate endpoints.

End point values	Part B2: M6620 60 mg/m^2 + Irinotecan 180 mg/m^2	Part B2: M6620 90 mg/m^2 + Irinotecan 180 mg/m^2
Number of subjects analysed	0 ^[54]	0 ^[55]
Units: hours
geometric mean (geometric coefficient of variation)	( )	( )

Notes
[54] - As per revised planned analysis, pharmacokinetic parameters for Part B2 was not assessed.
[55] - As per revised planned analysis, pharmacokinetic parameters for Part B2 was not assessed.

No statistical analyses for this end point

Secondary: Part B2: Percentage of Subjects with Objective Tumor Response (OR) as Evaluated by Response Criteria Evaluation in Solid Tumors (RECIST) 1.1

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End point title

Part B2: Percentage of Subjects with Objective Tumor Response (OR) as Evaluated by Response Criteria Evaluation in Solid Tumors (RECIST) 1.1 ^[56]

End point description

End point type

Secondary

End point timeframe

Time from first dose of study treatment up to 1.6 years

Notes
[56] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: In this endpoint, we have reported data for Part B2 arms only. For Parts A1, A2, B1, C1, C2 and C3 arms we have created separate endpoints.

End point values	Part B2: M6620 60 mg/m^2 + Irinotecan 180 mg/m^2	Part B2: M6620 90 mg/m^2 + Irinotecan 180 mg/m^2
Number of subjects analysed	0 ^[57]	0 ^[58]
Units: percentage of subjects
number (confidence interval 90%)	( to )	( to )

Notes
[57] - OR was not calculated as Part B2 was discontinued after observing toxicities at first dose level.
[58] - OR was not calculated as Part B2 was discontinued after observing toxicities at first dose level.

No statistical analyses for this end point

Secondary: Part C2: Percentage of Subjects with Objective Response (OR)

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End point title

Part C2: Percentage of Subjects with Objective Response (OR) ^[59]

End point description

OR was defined as the percentage of subjects who had achieved partial response (PR) or complete response (CR) as the best overall response according to according to Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST v1.1). CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the sum of the longest diameter (SLD) of all lesions. mFAS: all enrolled subjects who satisfy both of following conditions:1) Received at least 1 dose of study drug (M6620, gemcitabine, cisplatin/carboplatin with the actual amount greater than [>] 0 mg and/the duration of infusion > 0 minutes; 2) Had a Baseline scan of disease assessment (Computed tomography [CT]/Magnetic resonance imaging [MRI]) with a measurable target lesion (sum of diameters of all target lesions > 0 millimeter [mm]).

End point type

Secondary

End point timeframe

Time from first dose of study treatment up to 4.3 years

Notes
[59] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: In this endpoint, the data was planned to be reported for Part C2 arm only.

End point values	Part C2: M6620 140 mg/m^2 + Cisplatin 75 mg/m^2
Number of subjects analysed	47
Units: percentage of subjects
number (confidence interval 90%)	23.4 (13.7 to 35.8)

No statistical analyses for this end point

Secondary: Parts C1, C2, C3: Progression Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)

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End point title

Parts C1, C2, C3: Progression Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) ^[60]

End point description

PFS according to RECIST v1.1 was defined as the time from the date of the first dose of a study drug to the date of the first documentation of progressive disease (PD) or death due to any cause, whichever occurs first. PD was defined as at least a 20 percent (%) increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions. mFAS: all enrolled subjects who satisfy both of following conditions:1) Received at least 1 dose of study drug (M6620, gemcitabine, cisplatin/carboplatin with the actual amount greater than [>] 0 mg and/the duration of infusion > 0 minutes; 2) Had a Baseline scan of disease assessment (Computed tomography [CT]/Magnetic resonance imaging [MRI]) with a measurable target lesion (sum of diameters of all target lesions > 0 millimeter [mm]).

End point type

Secondary

End point timeframe

Time from first dose of study treatment to 4.3 years

Notes
[60] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: In this endpoint, the data was planned to be reported for Parts C1, C2 and C3 arms only .

End point values	Part C1: M6620 210 mg/m^2 + Gemcitabine 1000 mg/m^2	Part C2: M6620 140 mg/m^2 + Cisplatin 75 mg/m^2	Part C3: M6620 140 mg/m^2 + Cisplatin 75 mg/m^2	Part C3: M6620 90 mg/m^2 + Carboplatin AUC 5 mg∙min/mL
Number of subjects analysed	38	47	2	13
Units: months
median (confidence interval 90%)	4.0 (3.2 to 5.0)	4.0 (2.8 to 6.0)	3.3 (1.2 to 5.3)	1.9 (1.4 to 2.1)

No statistical analyses for this end point

Secondary: Parts C1, C2, C3: Duration of Response (DoR)

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End point title

Parts C1, C2, C3: Duration of Response (DoR) ^[61]

End point description

DoR was calculated only for those subjects who achieved a CR or PR and was measured from the time the response criteria were first met for CR/PR (whichever was recorded first) until the first date that recurrent or PD was objectively documented. FAS: all enrolled subjects who satisfy both of following conditions: 1) Received at least 1 dose of study drug (M6620, gemcitabine, cisplatin/carboplatin with the actual amount greater than [>] 0 mg and/the duration of infusion > 0 minutes; 2) Had a Baseline scan of disease assessment (Computed tomography [CT]/Magnetic resonance imaging [MRI]) with a measurable target lesion (sum of diameters of all target lesions > 0 millimeter [mm]). As there were no responders (CR or PR) in Part C3 (mFAS), the analysis of DoR is presented for Parts C1 and C2 only. Here, "number of subjects snalyzed" signifies those subjects who were evaluable for this endpoint .

End point type

Secondary

End point timeframe

Time from first dose of study treatment to 4.3 years

Notes
[61] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: In this endpoint, the data was planned to be reported for Parts C1, C2 and C3 arms only .

End point values	Part C1: M6620 210 mg/m^2 + Gemcitabine 1000 mg/m^2	Part C2: M6620 140 mg/m^2 + Cisplatin 75 mg/m^2	Part C3: M6620 140 mg/m^2 + Cisplatin 75 mg/m^2	Part C3: M6620 90 mg/m^2 + Carboplatin AUC 5 mg∙min/mL
Number of subjects analysed	4	11	0 ^[62]	0 ^[63]
Units: months
median (full range (min-max))	6.0 (3.6 to 13.2)	6.0 (3.0 to 28.6)	( to )	( to )

Notes
[62] - None of subjects showed complete response or partial response.
[63] - None of subjects showed complete response or partial response.

No statistical analyses for this end point

Secondary: Parts C1, C2, C3: Overall Survival (OS)

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End point title

Parts C1, C2, C3: Overall Survival (OS) ^[64]

End point description

OS time was defined as the time from the date of the first dose of a study drug to death due to any cause. mFAS: all enrolled subjects who satisfy both of following conditions:1) Received at least 1 dose of study drug (M6620, gemcitabine, cisplatin/carboplatin with the actual amount greater than [>] 0 mg and/the duration of infusion > 0 minutes; 2) Had a Baseline scan of disease assessment (Computed tomography [CT]/Magnetic resonance imaging [MRI]) with a measurable target lesion (sum of diameters of all target lesions > 0 millimeter [mm]).

End point type

Secondary

End point timeframe

Time from first dose of study treatment to 4.3 years

Notes
[64] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: In this endpoint, the data was planned to be reported for Parts C1, C2 and C3 arms only .

End point values	Part C1: M6620 210 mg/m^2 + Gemcitabine 1000 mg/m^2	Part C2: M6620 140 mg/m^2 + Cisplatin 75 mg/m^2	Part C3: M6620 140 mg/m^2 + Cisplatin 75 mg/m^2	Part C3: M6620 90 mg/m^2 + Carboplatin AUC 5 mg∙min/mL
Number of subjects analysed	38	47	2	13
Units: months
median (full range (min-max))	7.4 (0.8 to 28.2)	12.4 (1.4 to 31.6)	7.0 (6.3 to 7.0)	5.5 (0.8 to 16.4)

No statistical analyses for this end point

Secondary: Parts C1, C2, C3: Percentage of Subjects with Clinical benefit (Complete Response (CR) + Partial Response (PR) + Stable Disease (SD) of 6 months or greater)

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End point title

Parts C1, C2, C3: Percentage of Subjects with Clinical benefit (Complete Response (CR) + Partial Response (PR) + Stable Disease (SD) of 6 months or greater) ^[65]

End point description

Clinical benefit rate was defined as the proportion of subjects who achieved a BOR of CR, PR or SD greater than or equal to [>=] 6 months. mFAS: all enrolled subjects who satisfy both of following conditions:1) Received at least 1 dose of study drug (M6620, gemcitabine, cisplatin/carboplatin with the actual amount greater than [>] 0 mg and/the duration of infusion > 0 minutes; 2) Had a Baseline scan of disease assessment (Computed tomography [CT]/Magnetic resonance imaging [MRI]) with a measurable target lesion (sum of diameters of all target lesions > 0 millimeter [mm]).

End point type

Secondary

End point timeframe

Time from first dose of study treatment to 4.3 years

Notes
[65] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: In this endpoint, the data was planned to be reported for Parts C1, C2 and C3 arms only .

End point values	Part C1: M6620 210 mg/m^2 + Gemcitabine 1000 mg/m^2	Part C2: M6620 140 mg/m^2 + Cisplatin 75 mg/m^2	Part C3: M6620 140 mg/m^2 + Cisplatin 75 mg/m^2	Part C3: M6620 90 mg/m^2 + Carboplatin AUC 5 mg∙min/mL
Number of subjects analysed	38	47	2	13
Units: percentage of subjects
number (confidence interval 90%)	15.8 (7.1 to 28.8)	27.7 (17.2 to 40.3)	0 (0.0 to 77.6)	0 (0.0 to 20.6)

No statistical analyses for this end point

Secondary: Parts C1, C2 and C3: Maximum Observed Plasma Concentration (Cmax) of M6620

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End point title

Parts C1, C2 and C3: Maximum Observed Plasma Concentration (Cmax) of M6620 ^[66]

End point description

Cmax was obtained directly from the concentration versus time curve. PAS included all subjects who received at least 1 dose of M6620 (with the actual amount > 0 mg and/or the duration of infusion > 0 minutes), and provided at least 1 measurable post-dose concentration. Here, "number of subjects analyzed" signifies those subjects who were evaluable for this endpoint at given time points. Here, "99999" signifies that geometric coefficient of variation was not calculated.

End point type

Secondary

End point timeframe

Pre-infusion, 0.5, 1, 2, 3 and 7 hours after end of infusion (EOI) on Cycle 1 Day 2 (each cycle is of 21 days)

Notes
[66] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: In this endpoint, we have reported data for Parts C1, C2 and C3 arms only. For Part A1, A2, B1 and B2 arms we have created separate endpoints.

End point values	Part C1: M6620 210 mg/m^2 + Gemcitabine 1000 mg/m^2	Part C2: M6620 140 mg/m^2 + Cisplatin 75 mg/m^2	Part C3: M6620 140 mg/m^2 + Cisplatin 75 mg/m^2	Part C3: M6620 90 mg/m^2 + Carboplatin AUC 5 mg∙min/mL
Number of subjects analysed	35	37	2	12
Units: nanogram per milliliter (ng/mL)
geometric mean (geometric coefficient of variation)	882 ( 55.2 )	555 ( 42.9 )	683 ( 99999 )	528 ( 46.9 )

No statistical analyses for this end point

Secondary: Parts C1, C2 and C3: Area Under the Plasma Concentration-Time Curve from Time Zero to the Last Sampling Time (tlast) of M6620

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End point title

Parts C1, C2 and C3: Area Under the Plasma Concentration-Time Curve from Time Zero to the Last Sampling Time (tlast) of M6620 ^[67]

End point description

Area under the plasma concentration versus time curve from time zero to the last sampling time t at which the concentration was at or above the lower limit of quantification (LLQ). AUC0-t was to be calculated according to the mixed log-linear trapezoidal rule. PAS included all subjects who received at least 1 dose of M6620 (with the actual amount > 0 mg and/or the duration of infusion > 0 minutes), and provided at least 1 measurable post-dose concentration. Here, "number of subjects analyzed" signifies those subjects who were evaluable for this endpoint at given time points. Here, "3.3333" signifies that median was not calculated.

End point type

Secondary

End point timeframe

Pre-infusion, 0.5, 1, 2, 3 and 7 hours after end of infusion (EOI) on Cycle 1 Day 2 (each cycle is of 21 days)

Notes
[67] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: In this endpoint, we have reported data for Parts C1, C2 and C3 arms only. For Part A1, A2, B1 and B2 arms we have created separate endpoints.

End point values	Part C1: M6620 210 mg/m^2 + Gemcitabine 1000 mg/m^2	Part C2: M6620 140 mg/m^2 + Cisplatin 75 mg/m^2	Part C3: M6620 140 mg/m^2 + Cisplatin 75 mg/m^2	Part C3: M6620 90 mg/m^2 + Carboplatin AUC 5 mg∙min/mL
Number of subjects analysed	35	37	2	12
Units: hours
median (full range (min-max))	4.00 (3.00 to 8.00)	4.00 (3.67 to 8.07)	3.3333 (2.00 to 4.00)	4.03 (3.68 to 8.00)

No statistical analyses for this end point

Secondary: Parts C1, C2 and C3: Time to Reach Maximum Plasma Concentration (Tmax) of M6620

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End point title

Parts C1, C2 and C3: Time to Reach Maximum Plasma Concentration (Tmax) of M6620 ^[68]

End point description

Tmax is time to reach maximum observed plasma concentration obtained directly from the concentration versus time curve. PAS included all subjects who received at least 1 dose of M6620 (with the actual amount > 0 mg and/or the duration of infusion > 0 minutes), and provided at least 1 measurable post-dose concentration. Here, "number of subjects analyzed" signifies those subjects who were evaluable for this endpoint at given time points.

End point type

Secondary

End point timeframe

Pre-infusion, 0.5, 1, 2, 3 and 7 hours after end of infusion (EOI) on Cycle 1 Day 2 (each cycle is of 21 days)

Notes
[68] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: In this endpoint, we have reported data for Parts C1, C2 and C3 arms only. For Part A1, A2, B1 and B2 arms we have created separate endpoints.

End point values	Part C1: M6620 210 mg/m^2 + Gemcitabine 1000 mg/m^2	Part C2: M6620 140 mg/m^2 + Cisplatin 75 mg/m^2	Part C3: M6620 140 mg/m^2 + Cisplatin 75 mg/m^2	Part C3: M6620 90 mg/m^2 + Carboplatin AUC 5 mg∙min/mL
Number of subjects analysed	35	37	2	12
Units: hours
median (full range (min-max))	0.917 (0.483 to 2.28)	0.917 (0.500 to 2.00)	0.742 (0.533 to 0.950)	0.967 (0.467 to 1.23)

No statistical analyses for this end point

Secondary: Parts C1, C2 and C3: Area Under the Plasma Concentration-Time Curve From Time Zero to 4 hours [hr] (AUC0-4hr) of of M6620

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End point title

Parts C1, C2 and C3: Area Under the Plasma Concentration-Time Curve From Time Zero to 4 hours [hr] (AUC0-4hr) of of M6620 ^[69]

End point description

Area under the plasma concentration-time curve from time 0 to 4 hours post-dose (AUC0-4) was calculated using the linear trapezoidal rule. PAS included all subjects who received at least 1 dose of M6620 (with the actual amount > 0 mg and/or the duration of infusion > 0 minutes), and provided at least 1 measurable post-dose concentration. Here, "number of subjects analyzed" signifies those subjects who were evaluable for this endpoint at given time points. Here, "99999" signifies that geometric coefficient of variation was not calculated.

End point type

Secondary

End point timeframe

Pre-infusion, 0.5, 1, 2, 3 and 4 hours after end of infusion (EOI) on Cycle 1 Day 2 (each cycle is of 21 days)

Notes
[69] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: In this endpoint, we have reported data for Parts C1, C2 and C3 arms only. For Part A1, A2, B1 and B2 arms we have created separate endpoints.

End point values	Part C1: M6620 210 mg/m^2 + Gemcitabine 1000 mg/m^2	Part C2: M6620 140 mg/m^2 + Cisplatin 75 mg/m^2	Part C3: M6620 140 mg/m^2 + Cisplatin 75 mg/m^2	Part C3: M6620 90 mg/m^2 + Carboplatin AUC 5 mg∙min/mL
Number of subjects analysed	35	34	2	12
Units: ng*hr/mL
geometric mean (geometric coefficient of variation)	1600 ( 35.8 )	1110 ( 26.4 )	1030 ( 99999 )	693 ( 32.9 )

No statistical analyses for this end point

Secondary: Parts C1, C2 and C3: Area Under the Plasma Concentration-Time Curve From Time Zero to 8 hours [hr] (AUC0-8 hr) of of M6620

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End point title

Parts C1, C2 and C3: Area Under the Plasma Concentration-Time Curve From Time Zero to 8 hours [hr] (AUC0-8 hr) of of M6620 ^[70]

End point description

Area under the plasma concentration-time curve from time 0 to 8 hours post-dose (AUC0-8) was calculated using the linear trapezoidal rule. PAS included all subjects who received at least 1 dose of M6620 (with the actual amount > 0 mg and/or the duration of infusion > 0 minutes), and provided at least 1 measurable post-dose concentration. Here, "number of subjects analyzed" signifies those subjects who were evaluable for this endpoint at given time points. Here, "99999" signifies that geometric coefficient of variation was not calculated.

End point type

Secondary

End point timeframe

Pre-infusion, 0.5, 1, 2, 3 and 7 hours after end of infusion (EOI) on Cycle 1 Day 2 (each cycle is of 21 days)

Notes
[70] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: In this endpoint, we have reported data for Parts C1, C2 and C3 arms only. For Part A1, A2, B1 and B2 arms we have created separate endpoints.

End point values	Part C1: M6620 210 mg/m^2 + Gemcitabine 1000 mg/m^2	Part C2: M6620 140 mg/m^2 + Cisplatin 75 mg/m^2	Part C3: M6620 140 mg/m^2 + Cisplatin 75 mg/m^2	Part C3: M6620 90 mg/m^2 + Carboplatin AUC 5 mg∙min/mL
Number of subjects analysed	3	2	0 ^[71]	2
Units: ng*hr/mL
geometric mean (geometric coefficient of variation)	2000 ( 10.9 )	1800 ( 99999 )	( )	970 ( 99999 )

Notes
[71] - None of subjects were evaluable at the given timepoints.

No statistical analyses for this end point

Secondary: Parts C1, C2 and C3: Area Under the Plasma Concentration-Time Curve From Time Zero to Last Sampling Time (AUC0-t) of of M6620

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End point title

Parts C1, C2 and C3: Area Under the Plasma Concentration-Time Curve From Time Zero to Last Sampling Time (AUC0-t) of of M6620 ^[72]

End point description

End point type

Secondary

End point timeframe

Pre-infusion, 0.5, 1, 2, 3, and 7 hours after end of infusion (EOI) on Cycle 1 Day 2 (each cycle is of 21 days)

Notes
[72] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: In this endpoint, we have reported data for Parts C1, C2 and C3 arms only. For Part A1, A2, B1 and B2 arms we have created separate endpoints.

End point values	Part C1: M6620 210 mg/m^2 + Gemcitabine 1000 mg/m^2	Part C2: M6620 140 mg/m^2 + Cisplatin 75 mg/m^2	Part C3: M6620 140 mg/m^2 + Cisplatin 75 mg/m^2	Part C3: M6620 90 mg/m^2 + Carboplatin AUC 5 mg∙min/mL
Number of subjects analysed	35	37	2	12
Units: ng*hr/mL
geometric mean (geometric coefficient of variation)	1660 ( 35.8 )	1110 ( 28.8 )	910 ( 99999 )	730 ( 36.0 )

No statistical analyses for this end point

Secondary: Parts C1, C2 and C3: Dose Normalized Maximum Concentration (Cmax/Dose_mg ) of M6620

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End point title

Parts C1, C2 and C3: Dose Normalized Maximum Concentration (Cmax/Dose_mg ) of M6620 ^[73]

End point description

Dose normalized was calculated as Cmax obtained directly from the concentration versus time curve divided by dose. PAS included all subjects who received at least 1 dose of M6620 (with the actual amount > 0 mg and/or the duration of infusion > 0 minutes), and provided at least 1 measurable post-dose concentration. Here, "number of subjects analyzed" signifies those subjects who were evaluable for this endpoint at given time points. Here, "99999" signifies that geometric coefficient of variation was not calculated.

End point type

Secondary

End point timeframe

Pre-infusion, 0.5, 1, 2, 3, and 7 hours after end of infusion (EOI) on Cycle 1 Day 2 (each cycle is of 21 days)

Notes
[73] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: In this endpoint, we have reported data for Parts C1, C2 and C3 arms only. For Part A1, A2, B1 and B2 arms we have created separate endpoints.

End point values	Part C1: M6620 210 mg/m^2 + Gemcitabine 1000 mg/m^2	Part C2: M6620 140 mg/m^2 + Cisplatin 75 mg/m^2	Part C3: M6620 140 mg/m^2 + Cisplatin 75 mg/m^2	Part C3: M6620 90 mg/m^2 + Carboplatin AUC 5 mg∙min/mL
Number of subjects analysed	35	37	2	12
Units: ng/mL/mg
geometric mean (geometric coefficient of variation)	2.37 ( 52.4 )	2.18 ( 44.6 )	2.72 ( 99999 )	3.24 ( 54.4 )

No statistical analyses for this end point

Secondary: Parts C1, C2 and C3: Dose Normalized Maximum Concentration (Cmax/Dose_mg/m^2) of M6620

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End point title

Parts C1, C2 and C3: Dose Normalized Maximum Concentration (Cmax/Dose_mg/m^2) of M6620 ^[74]

End point description

End point type

Secondary

End point timeframe

Pre-infusion, 0.5, 1, 2, 3, and 7 hours after end of infusion (EOI) on Cycle 1 Day 2 (each cycle is of 21 days)

Notes
[74] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: In this endpoint, we have reported data for Parts C1, C2 and C3 arms only. For Part A1, A2, B1 and B2 arms we have created separate endpoints.

End point values	Part C1: M6620 210 mg/m^2 + Gemcitabine 1000 mg/m^2	Part C2: M6620 140 mg/m^2 + Cisplatin 75 mg/m^2	Part C3: M6620 140 mg/m^2 + Cisplatin 75 mg/m^2	Part C3: M6620 90 mg/m^2 + Carboplatin AUC 5 mg∙min/mL
Number of subjects analysed	35	37	2	12
Units: ng/mL/(mg/m^2)
geometric mean (geometric coefficient of variation)	4.28 ( 54.6 )	3.97 ( 42.9 )	4.89 ( 99999 )	5.88 ( 47.1 )

No statistical analyses for this end point

Secondary: Parts C1, C2 and C3: Dose Normalized Area Under The Concentration-Time Curve (AUC) from Start of Infusion to The 4 hour Sampling Time After Start of Infusion (AUC0-4h/Dose_mg) of M6620

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End point title

Parts C1, C2 and C3: Dose Normalized Area Under The Concentration-Time Curve (AUC) from Start of Infusion to The 4 hour Sampling Time After Start of Infusion (AUC0-4h/Dose_mg) of M6620 ^[75]

End point description

Dose normalized was calculated as area under the plasma concentration-time curve from time zero to 4 hour postdose divided by dose. PAS included all subjects who received at least 1 dose of M6620 (with the actual amount > 0 mg and/or the duration of infusion > 0 minutes), and provided at least 1 measurable post-dose concentration. Here, "number of subjects analyzed" signifies those subjects who were evaluable for this endpoint at given time points. Here, "99999" signifies that geometric coefficient of variation was not calculated.

End point type

Secondary

End point timeframe

Pre-infusion, 0.5, 1, 2, 3 and 4 hours after end of infusion (EOI) on Cycle 1 Day 2 (each cycle is of 21 days)

Notes
[75] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: In this endpoint, we have reported data for Parts C1, C2 and C3 arms only. For Part A1, A2, B1 and B2 arms we have created separate endpoints.

End point values	Part C1: M6620 210 mg/m^2 + Gemcitabine 1000 mg/m^2	Part C2: M6620 140 mg/m^2 + Cisplatin 75 mg/m^2	Part C3: M6620 140 mg/m^2 + Cisplatin 75 mg/m^2	Part C3: M6620 90 mg/m^2 + Carboplatin AUC 5 mg∙min/mL
Number of subjects analysed	35	34	2	12
Units: ng*h/mL/mg
geometric mean (geometric coefficient of variation)	4.29 ( 37.0 )	4.41 ( 26.1 )	4.11 ( 99999 )	4.24 ( 39.8 )

No statistical analyses for this end point

Secondary: Parts C1, C2 and C3: Dose Normalized Area Under the Concentration-Time Curve (AUC) from Start of Infusion to the 4 hour Sampling Time After Start of Infusion (AUC0-4h/Dose_mg/m^2) of M6620

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End point title

Parts C1, C2 and C3: Dose Normalized Area Under the Concentration-Time Curve (AUC) from Start of Infusion to the 4 hour Sampling Time After Start of Infusion (AUC0-4h/Dose_mg/m^2) of M6620 ^[76]

End point description

Dose normalized was calculated as area under the plasma concentration-time curve from rom start of infusion to the 4 hour postdose divided by dose. PAS included all subjects who received at least 1 dose of M6620 (with the actual amount > 0 mg and/or the duration of infusion > 0 minutes), and provided at least 1 measurable post-dose concentration. Here, "number of subjects analyzed" signifies those subjects who were evaluable for this endpoint at given time points. Here, "99999" signifies that geometric coefficient of variation was not calculated.

End point type

Secondary

End point timeframe

Pre-infusion, 0.5, 1, 2, 3 and 4 hours after end of infusion (EOI) on Cycle 1 Day 2 (each cycle is of 21 days)

Notes
[76] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: In this endpoint, we have reported data for Parts C1, C2 and C3 arms only. For Part A1, A2, B1 and B2 arms we have created separate endpoints.

End point values	Part C1: M6620 210 mg/m^2 + Gemcitabine 1000 mg/m^2	Part C2: M6620 140 mg/m^2 + Cisplatin 75 mg/m^2	Part C3: M6620 140 mg/m^2 + Cisplatin 75 mg/m^2	Part C3: M6620 90 mg/m^2 + Carboplatin AUC 5 mg∙min/mL
Number of subjects analysed	35	34	2	12
Units: ng*h/mL/(mg/m^2)
geometric mean (geometric coefficient of variation)	7.76 ( 36.7 )	7.95 ( 26.4 )	7.40 ( 99999 )	7.71 ( 33.0 )

No statistical analyses for this end point

Secondary: Parts C1, C2 and C3: Dose Normalized Area Under the Concentration-Time Curve (AUC) from Start of Infusion to the 8 hour Sampling Time After Start of Infusion (AUC0-8h/Dose_mg) of M6620

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End point title

Parts C1, C2 and C3: Dose Normalized Area Under the Concentration-Time Curve (AUC) from Start of Infusion to the 8 hour Sampling Time After Start of Infusion (AUC0-8h/Dose_mg) of M6620 ^[77]

End point description

Dose normalized was calculated as area under the plasma concentration-time curve from time zero to 8 hour postdose divided by dose. PAS included all subjects who received at least 1 dose of M6620 (with the actual amount > 0 mg and/or the duration of infusion > 0 minutes), and provided at least 1 measurable post-dose concentration. Here, "number of subjects analyzed" signifies those subjects who were evaluable for this endpoint at given time points. Here, "99999" signifies that geometric coefficient of variation was not calculated.

End point type

Secondary

End point timeframe

Pre-infusion, 0.5, 1, 2, 3 and 7 hours after end of infusion (EOI) on Cycle 1 Day 2 (each cycle is of 21 days)

Notes
[77] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: In this endpoint, we have reported data for Parts C1, C2 and C3 arms only. For Part A1, A2, B1 and B2 arms we have created separate endpoints.

End point values	Part C1: M6620 210 mg/m^2 + Gemcitabine 1000 mg/m^2	Part C2: M6620 140 mg/m^2 + Cisplatin 75 mg/m^2	Part C3: M6620 140 mg/m^2 + Cisplatin 75 mg/m^2	Part C3: M6620 90 mg/m^2 + Carboplatin AUC 5 mg∙min/mL
Number of subjects analysed	3	2	0 ^[78]	2
Units: ng*h/mL/mg
geometric mean (geometric coefficient of variation)	5.43 ( 10.1 )	7.53 ( 99999 )	( )	5.63 ( 99999 )

Notes
[78] - None of the subjects were evaluable at given time points.

No statistical analyses for this end point

Secondary: Parts C1, C2 and C3: Dose Normalized Area Under the Concentration-Time Curve (AUC) from Start of Infusion to the 8 hour Sampling Time After Start of Infusion (AUC0-8h/Dose_mg/m^2) of M6620

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End point title

Parts C1, C2 and C3: Dose Normalized Area Under the Concentration-Time Curve (AUC) from Start of Infusion to the 8 hour Sampling Time After Start of Infusion (AUC0-8h/Dose_mg/m^2) of M6620 ^[79]

End point description

Dose normalized was calculated as area under the plasma concentration-time curve from time zero to 8 hours postdose divided by dose. PAS included all subjects who received at least 1 dose of M6620 (with the actual amount > 0 mg and/or the duration of infusion > 0 minutes), and provided at least 1 measurable post-dose concentration. Here, "number of subjects analyzed" signifies those subjects who were evaluable for this endpoint at given time points. Here, "99999" signifies that geometric coefficient of variation was not calculated.

End point type

Secondary

End point timeframe

Pre-infusion, 0.5, 1, 2, 3 and 7 hours after end of infusion (EOI) on Cycle 1 Day 2 (each cycle is of 21 days)

Notes
[79] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: In this endpoint, we have reported data for Parts C1, C2 and C3 arms only. For Part A1, A2, B1 and B2 arms we have created separate endpoints.

End point values	Part C1: M6620 210 mg/m^2 + Gemcitabine 1000 mg/m^2	Part C2: M6620 140 mg/m^2 + Cisplatin 75 mg/m^2	Part C3: M6620 140 mg/m^2 + Cisplatin 75 mg/m^2	Part C3: M6620 90 mg/m^2 + Carboplatin AUC 5 mg∙min/mL
Number of subjects analysed	3	2	0 ^[80]	2
Units: ng*h/mL/(mg/m^2)
geometric mean (geometric coefficient of variation)	9.54 ( 10.9 )	12.9 ( 99999 )	( )	10.8 ( 99999 )

Notes
[80] - None of the subjects were evaluable at given time points.

No statistical analyses for this end point

Secondary: Parts C1, C2 and C3: Dose Normalized Area Under Concentarion-Time Curve (AUC) from Time Zero to the Last Sampling Time (tlast) (AUC0-t/Dose_mg) of M6620

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End point title

Parts C1, C2 and C3: Dose Normalized Area Under Concentarion-Time Curve (AUC) from Time Zero to the Last Sampling Time (tlast) (AUC0-t/Dose_mg) of M6620 ^[81]

End point description

End point type

Secondary

End point timeframe

Pre-infusion, 0.5, 1, 2, 3, and 7 hours after end of infusion (EOI) on Cycle 1 Day 2 (each cycle is of 21 days)

Notes
[81] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: In this endpoint, we have reported data for Parts C1, C2 and C3 arms only. For Part A1, A2, B1 and B2 arms we have created separate endpoints.

End point values	Part C1: M6620 210 mg/m^2 + Gemcitabine 1000 mg/m^2	Part C2: M6620 140 mg/m^2 + Cisplatin 75 mg/m^2	Part C3: M6620 140 mg/m^2 + Cisplatin 75 mg/m^2	Part C3: M6620 90 mg/m^2 + Carboplatin AUC 5 mg∙min/mL
Number of subjects analysed	35	37	2	12
Units: ng*h/mL/mg
geometric mean (geometric coefficient of variation)	4.47 ( 36.3 )	4.36 ( 30.6 )	3.62 ( 99999 )	4.47 ( 41.7 )

No statistical analyses for this end point

Secondary: Parts C1, C2 and C3: Dose Normalized Area Under Concentarion-Time Curve (AUC) from Time Zero to the Last Sampling Time (tlast) (AUC0-t/Dose_mg/m^2) of M6620

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End point title

Parts C1, C2 and C3: Dose Normalized Area Under Concentarion-Time Curve (AUC) from Time Zero to the Last Sampling Time (tlast) (AUC0-t/Dose_mg/m^2) of M6620 ^[82]

End point description

End point type

Secondary

End point timeframe

Pre-infusion, 0.5, 1, 2, 3, and 7 hours after end of infusion (EOI) on Cycle 1 Day 2 (each cycle is of 21 days)

Notes
[82] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: In this endpoint, we have reported data for Parts C1, C2 and C3 arms only. For Part A1, A2, B1 and B2 arms we have created separate endpoints.

End point values	Part C1: M6620 210 mg/m^2 + Gemcitabine 1000 mg/m^2	Part C2: M6620 140 mg/m^2 + Cisplatin 75 mg/m^2	Part C3: M6620 140 mg/m^2 + Cisplatin 75 mg/m^2	Part C3: M6620 90 mg/m^2 + Carboplatin AUC 5 mg∙min/mL
Number of subjects analysed	35	37	2	12
Units: ng*h/mL/(mg/m^2)
geometric mean (geometric coefficient of variation)	8.08 ( 36.7 )	7.92 ( 28.8 )	6.51 ( 99999 )	8.12 ( 36.1 )

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

Parts A1, A2 and B1: Time from first dose of study treatment up to 4.6 years; Part B2: Time from first dose of study treatment up to 1.6 years; Parts C1, C2 and C3: Time from first dose of study treatment up to 4.3 years.

Adverse event reporting additional description

Non-serious Adverse Event Section: Treatment-Emergent Adverse Events were reported for Parts A1, A2 and B1 and Non-serious Adverse event for Parts B2, C1, C2 and C3 with same threshold frequency (0%).

Assessment type

Non-systematic

Dictionary name

MedDRA

Dictionary version

18,22.1&21

Reporting group title

Part A1: M6620 18 mg/m^2 + Gemcitabine 875 mg/m^2

Reporting group description

Reporting group title

Part A1: M6620 36 mg/m^2 + Gemcitabine 875 mg/m^2

Reporting group description

Reporting group title

Part A1: M6620 60 mg/m^2 + Gemcitabine 875 mg/m^2

Reporting group description

Reporting group title

Part A1: M6620 72 mg/m^2 + Gemcitabine 875 mg/m^2

Reporting group description

Reporting group title

Part A1: M6620 90 mg/m^2 + Gemcitabine 500 mg/m^2

Reporting group description

Reporting group title

Part A1: M6620 140 mg/m^2 + Gemcitabine 500 mg/m^2

Reporting group description

Reporting group title

Part A1: M6620 210 mg/m^2 + Gemcitabine 500 mg/m^2

Reporting group description

Reporting group title

Part A1: M6620 210 mg/m^2 + Gemcitabine 750 mg/m^2

Reporting group description

Reporting group title

Part A1: M6620 210 mg/m^2 + Gemcitabine 875 mg/m^2

Reporting group description

Reporting group title

Part A1: M6620 210 mg/m^2 + Gemcitabine 1000 mg/m^2

Reporting group description

Reporting group title

Part A2: M6620 90 mg/m^2 + Gemcitabine + Cisplatin

Reporting group description

Subjects received intravenous infusion of M6620 at dose of 90 mg/m^2 approximately for 24 hours later on Days 2 and 9 in combination with Gemcitabine at a dose of 875 mg/m^2 on Days 1 and 8 and Cisplatin at a dose of 60 mg/m^2 on Day 1, of a 21-day cycle up to 41 weeks.

Reporting group title

Part A2: M6620 120 mg/m^2 + Gemcitabine + Cisplatin

Reporting group description

Subjects received intravenous infusion of M6620 at dose of 120 mg/m^2 approximately for 24 hours later on Days 2 and 9 in combination with Gemcitabine at a dose of 875 mg/m^2 on Days 1 and 8 and Cisplatin at a dose of 60 mg/m^2 on Day 1, of a 21-day cycle up to 41 weeks.

Reporting group title

Part B1: M6620 140 mg/m^2

Reporting group description

Subjects received intravenous infusion of M6620 at dose of 140 mg/m^2 approximately for 24 hours later on Days 2 and 9 of a 21-day cycle up to 74 weeks.

Reporting group title

Part B1: M6620 90 mg/m^2 + Cisplatin 40 mg/m^2

Reporting group description

Subjects received intravenous infusion of M6620 at dose of 90 mg/m^2 approximately for 24 hours later on Days 2 and 9 in combination with Cisplatin at a dose of 40 mg/m^2 on Day 1, of a 21-day cycle up to 74 weeks.

Reporting group title

Part B1: M6620 140 mg/m^2 + Cisplatin 40 mg/m^2

Reporting group description

Subjects received intravenous infusion of M6620 at dose of 140mg/m^2 approximately for 24 hours later on Days 2 and 9 in combination with Cisplatin ata dose of 40 mg/m^2 on Day 1 of a 21-day cycle for up to 74 weeks.

Reporting group title

Part B1: M6620 210 mg/m^2 + Cisplatin 40 mg/m^2

Reporting group description

Subjects received intravenous infusion of M6620 at dose of 210 mg/m^2 approximately for 24 hours later on Days 2 and 9 in combination with Cisplatin at a dose of 40 mg/m^2 on Day 1 of a 21-day cycle up to 74 weeks.

Reporting group title

Part B1: M6620 210 mg/m^2 + Cisplatin 60 mg/m^2

Reporting group description

Reporting group title

Part B1: M6620 140 mg/m^2 + Cisplatin 75 mg/m^2

Reporting group description

Reporting group title

Part B1: M6620 210 mg/m^2 + Cisplatin 75 mg/m^2

Reporting group description

Subjects received intravenous infusion of M6620 at dose of 210 mg/m^2 approximately for 24 hours later on Days 2 and 9 in combination with Cisplatin at a dose of 75 mg/m^2 on Day 1 of a 21-day cycle up to 74 weeks.

Reporting group title

Part B2: M6620 60 mg/m^2 + Irinotecan 180 mg/m^2

Reporting group description

Subjects received intravenous infusion of M6620 at a dose of 60 mg/m^2, in combination with irinotecan at a dose of 180 mg/m^2 (over 90 minutes) on Days 1 and 15 of a 28-day cycle up to 72 weeks.

Reporting group title

Part B2: M6620 90 mg/m^2 + Irinotecan 180 mg/m^2

Reporting group description

Subjects received intravenous infusion of M6620 at a dose of 90 mg/m^2, in combination with irinotecan at a dose of 180 mg/m^2 (over 90 minutes) on Days 1 and 15 of a 28-day cycle up to 72 weeks.

Reporting group title

Part C1: M6620 210 mg/m^2 + Gemcitabine 1000 mg/m^2

Reporting group description

Reporting group title

Part C2: M6620 140 mg/m^2 + Cisplatin 75 mg/m^2

Reporting group description

Reporting group title

Part C3: M6620 140 mg/m^2 + Cisplatin 75 mg/m^2

Reporting group description

Reporting group title

Part C3: M6620 90 mg/m^2 + Carboplatin AUC 5 mg∙min/mL

Reporting group description

Subjects with platinum-resistant advanced SCLC received intravenous infusion of M6620 at a dose of 90 mg/m^2 on Days 2 and 9 in combination with Carboplatin area under concentration-time curve (AUC) at a dose of 5 milligrams.minute per milliliter on Day 1 of a 21-day cycle up to 27 weeks.

Part A1: M6620 18 mg/m^2 + Gemcitabine 875 mg/m^2

Part A1: M6620 36 mg/m^2 + Gemcitabine 875 mg/m^2

Part A1: M6620 60 mg/m^2 + Gemcitabine 875 mg/m^2

Part A1: M6620 72 mg/m^2 + Gemcitabine 875 mg/m^2

Part A1: M6620 90 mg/m^2 + Gemcitabine 500 mg/m^2

Part A1: M6620 140 mg/m^2 + Gemcitabine 500 mg/m^2

Part A1: M6620 210 mg/m^2 + Gemcitabine 500 mg/m^2

Part A1: M6620 210 mg/m^2 + Gemcitabine 750 mg/m^2

Part A1: M6620 210 mg/m^2 + Gemcitabine 875 mg/m^2

Part A1: M6620 210 mg/m^2 + Gemcitabine 1000 mg/m^2

Part A2: M6620 90 mg/m^2 + Gemcitabine + Cisplatin

Part A2: M6620 120 mg/m^2 + Gemcitabine + Cisplatin

Part B1: M6620 140 mg/m^2

Part B1: M6620 90 mg/m^2 + Cisplatin 40 mg/m^2

Part B1: M6620 140 mg/m^2 + Cisplatin 40 mg/m^2

Part B1: M6620 210 mg/m^2 + Cisplatin 40 mg/m^2

Part B1: M6620 210 mg/m^2 + Cisplatin 60 mg/m^2

Part B1: M6620 140 mg/m^2 + Cisplatin 75 mg/m^2

Part B1: M6620 210 mg/m^2 + Cisplatin 75 mg/m^2

Part B2: M6620 60 mg/m^2 + Irinotecan 180 mg/m^2

Part B2: M6620 90 mg/m^2 + Irinotecan 180 mg/m^2

Part C1: M6620 210 mg/m^2 + Gemcitabine 1000 mg/m^2

Part C2: M6620 140 mg/m^2 + Cisplatin 75 mg/m^2

Part C3: M6620 140 mg/m^2 + Cisplatin 75 mg/m^2

Part C3: M6620 90 mg/m^2 + Carboplatin AUC 5 mg∙min/mL

Total subjects affected by serious adverse events

subjects affected / exposed

2 / 3 (66.67%)

0 / 3 (0.00%)

2 / 4 (50.00%)

4 / 7 (57.14%)

3 / 6 (50.00%)

5 / 8 (62.50%)

2 / 3 (66.67%)

1 / 3 (33.33%)

3 / 7 (42.86%)

2 / 6 (33.33%)

3 / 6 (50.00%)

2 / 2 (100.00%)

1 / 4 (25.00%)

2 / 3 (66.67%)

0 / 3 (0.00%)

0 / 4 (0.00%)

4 / 10 (40.00%)

3 / 7 (42.86%)

2 / 3 (66.67%)

1 / 5 (20.00%)

2 / 3 (66.67%)

24 / 38 (63.16%)

15 / 47 (31.91%)

0 / 2 (0.00%)

3 / 13 (23.08%)

number of deaths (all causes)

number of deaths resulting from adverse events

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Metastases to central nervous system

subjects affected / exposed

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 8 (0.00%)

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 2 (0.00%)

1 / 4 (25.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 10 (0.00%)

0 / 7 (0.00%)

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 3 (0.00%)

0 / 38 (0.00%)

0 / 47 (0.00%)

0 / 2 (0.00%)

0 / 13 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Brain neoplasm

subjects affected / exposed

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 8 (0.00%)

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 10 (0.00%)

1 / 7 (14.29%)

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 3 (0.00%)

0 / 38 (0.00%)

0 / 47 (0.00%)

0 / 2 (0.00%)

0 / 13 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Metastases to liver

subjects affected / exposed

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 8 (0.00%)

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 10 (0.00%)

0 / 7 (0.00%)

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 3 (0.00%)

1 / 38 (2.63%)

0 / 47 (0.00%)

0 / 2 (0.00%)

0 / 13 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

1 / 1

0 / 0

Non-small cell lung cancer

subjects affected / exposed

0 / 3 (0.00%)

0 / 4 (0.00%)

1 / 7 (14.29%)

0 / 6 (0.00%)

0 / 8 (0.00%)

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 10 (0.00%)

0 / 7 (0.00%)

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 3 (0.00%)

0 / 38 (0.00%)

0 / 47 (0.00%)

0 / 2 (0.00%)

0 / 13 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

1 / 1

0 / 0

Vascular disorders

Hypovolaemic shock

subjects affected / exposed

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 8 (0.00%)

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 10 (0.00%)

0 / 7 (0.00%)

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 3 (0.00%)

1 / 38 (2.63%)

0 / 47 (0.00%)

0 / 2 (0.00%)

0 / 13 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

1 / 1

0 / 0

Superior vena cava syndrome

subjects affected / exposed

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 8 (0.00%)

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 10 (0.00%)

0 / 7 (0.00%)

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 3 (0.00%)

0 / 38 (0.00%)

0 / 47 (0.00%)

0 / 2 (0.00%)

1 / 13 (7.69%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Thrombosis

subjects affected / exposed

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 8 (0.00%)

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 10 (0.00%)

0 / 7 (0.00%)

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 3 (0.00%)

1 / 38 (2.63%)

0 / 47 (0.00%)

0 / 2 (0.00%)

0 / 13 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Deep vein thrombosis

subjects affected / exposed

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 8 (0.00%)

0 / 3 (0.00%)

1 / 7 (14.29%)

0 / 6 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 10 (0.00%)

0 / 7 (0.00%)

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 3 (0.00%)

0 / 38 (0.00%)

0 / 47 (0.00%)

0 / 2 (0.00%)

0 / 13 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

General disorders and administration site conditions

Pyrexia

subjects affected / exposed

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 7 (0.00%)

1 / 6 (16.67%)

3 / 8 (37.50%)

0 / 3 (0.00%)

0 / 7 (0.00%)

2 / 6 (33.33%)

0 / 6 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 10 (0.00%)

1 / 7 (14.29%)

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 3 (0.00%)

2 / 38 (5.26%)

2 / 47 (4.26%)

0 / 2 (0.00%)

0 / 13 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

3 / 3

0 / 0

2 / 2

0 / 0

0 / 1

0 / 0

2 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Influenza like illness

subjects affected / exposed

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

1 / 8 (12.50%)

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 10 (0.00%)

0 / 7 (0.00%)

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 3 (0.00%)

0 / 38 (0.00%)

0 / 47 (0.00%)

0 / 2 (0.00%)

0 / 13 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Chills

subjects affected / exposed

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 8 (0.00%)

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 10 (0.00%)

0 / 7 (0.00%)

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 3 (0.00%)

0 / 38 (0.00%)

1 / 47 (2.13%)

0 / 2 (0.00%)

0 / 13 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Malaise

subjects affected / exposed

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 8 (0.00%)

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 10 (0.00%)

0 / 7 (0.00%)

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 3 (0.00%)

1 / 38 (2.63%)

0 / 47 (0.00%)

0 / 2 (0.00%)

0 / 13 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Non-cardiac chest pain

subjects affected / exposed

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 8 (0.00%)

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 10 (0.00%)

0 / 7 (0.00%)

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 3 (0.00%)

1 / 38 (2.63%)

2 / 47 (4.26%)

0 / 2 (0.00%)

0 / 13 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Asthenia

subjects affected / exposed

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 8 (0.00%)

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 10 (0.00%)

0 / 7 (0.00%)

0 / 3 (0.00%)

0 / 5 (0.00%)

1 / 3 (33.33%)

0 / 38 (0.00%)

0 / 47 (0.00%)

0 / 2 (0.00%)

0 / 13 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Immune system disorders

Hypersensitivity

subjects affected / exposed

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

1 / 8 (12.50%)

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 10 (0.00%)

1 / 7 (14.29%)

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 3 (0.00%)

0 / 38 (0.00%)

0 / 47 (0.00%)

0 / 2 (0.00%)

0 / 13 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Reproductive system and breast disorders

Breast haematoma

subjects affected / exposed

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 8 (0.00%)

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 10 (0.00%)

0 / 7 (0.00%)

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 3 (0.00%)

0 / 38 (0.00%)

1 / 47 (2.13%)

0 / 2 (0.00%)

0 / 13 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Respiratory, thoracic and mediastinal disorders

Dyspnoea

subjects affected / exposed

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 8 (0.00%)

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

1 / 2 (50.00%)

0 / 4 (0.00%)

1 / 3 (33.33%)

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 10 (0.00%)

0 / 7 (0.00%)

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 3 (0.00%)

4 / 38 (10.53%)

2 / 47 (4.26%)

0 / 2 (0.00%)

0 / 13 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 4

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Hypoxia

subjects affected / exposed

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 8 (0.00%)

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

1 / 2 (50.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

1 / 10 (10.00%)

0 / 7 (0.00%)

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 3 (0.00%)

0 / 38 (0.00%)

2 / 47 (4.26%)

0 / 2 (0.00%)

0 / 13 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

1 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Pleural effusion

subjects affected / exposed

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 8 (0.00%)

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

1 / 2 (50.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 10 (0.00%)

0 / 7 (0.00%)

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 3 (0.00%)

1 / 38 (2.63%)

1 / 47 (2.13%)

0 / 2 (0.00%)

0 / 13 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Chronic obstructive pulmonary disease

subjects affected / exposed

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 8 (0.00%)

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 10 (0.00%)

0 / 7 (0.00%)

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 3 (0.00%)

1 / 38 (2.63%)

0 / 47 (0.00%)

0 / 2 (0.00%)

0 / 13 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Haemoptysis

subjects affected / exposed

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 8 (0.00%)

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 10 (0.00%)

0 / 7 (0.00%)

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 3 (0.00%)

1 / 38 (2.63%)

0 / 47 (0.00%)

0 / 2 (0.00%)

0 / 13 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

1 / 1

0 / 0

Pulmonary embolism

subjects affected / exposed

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 8 (0.00%)

0 / 3 (0.00%)

0 / 7 (0.00%)

1 / 6 (16.67%)

0 / 6 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 10 (0.00%)

0 / 7 (0.00%)

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 3 (0.00%)

1 / 38 (2.63%)

1 / 47 (2.13%)

0 / 2 (0.00%)

0 / 13 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

1 / 1

0 / 0

Pulmonary oedema

subjects affected / exposed

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 8 (0.00%)

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 10 (0.00%)

0 / 7 (0.00%)

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 3 (0.00%)

0 / 38 (0.00%)

1 / 47 (2.13%)

0 / 2 (0.00%)

0 / 13 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Respiratory failure

subjects affected / exposed

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 8 (0.00%)

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 10 (0.00%)

0 / 7 (0.00%)

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 3 (0.00%)

1 / 38 (2.63%)

0 / 47 (0.00%)

0 / 2 (0.00%)

0 / 13 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Stridor

subjects affected / exposed

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 8 (0.00%)

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 10 (0.00%)

0 / 7 (0.00%)

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 3 (0.00%)

1 / 38 (2.63%)

0 / 47 (0.00%)

0 / 2 (0.00%)

0 / 13 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Atelectasis

subjects affected / exposed

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 7 (0.00%)

1 / 6 (16.67%)

0 / 8 (0.00%)

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 10 (0.00%)

0 / 7 (0.00%)

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 3 (0.00%)

0 / 38 (0.00%)

0 / 47 (0.00%)

0 / 2 (0.00%)

0 / 13 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pleuritic pain

subjects affected / exposed

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 8 (0.00%)

0 / 3 (0.00%)

1 / 7 (14.29%)

0 / 6 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 10 (0.00%)

0 / 7 (0.00%)

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 3 (0.00%)

0 / 38 (0.00%)

0 / 47 (0.00%)

0 / 2 (0.00%)

0 / 13 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Investigations

Alanine aminotransferase increased

subjects affected / exposed

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 8 (0.00%)

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

1 / 10 (10.00%)

0 / 7 (0.00%)

1 / 3 (33.33%)

0 / 5 (0.00%)

0 / 3 (0.00%)

0 / 38 (0.00%)

0 / 47 (0.00%)

0 / 2 (0.00%)

0 / 13 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Aspartate aminotransferase increased

subjects affected / exposed

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 8 (0.00%)

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

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Clinical trials

Clinical Trial Results: An Open-label, First-in-Human Study of the Safety, Tolerability, and Pharmacokinetics of VX-970/M6620 in Combination with Cytotoxic Chemotherapy in Participants With Advanced Solid Tumors

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Parts A1, A2, B1: Number of Subjects with Treatment-Emergent Adverse Events (TEAEs)

Primary: Parts A1, A2, B1: Number of Subjects with Treatment-Emergent Adverse Events (TEAEs)

Primary: Parts A1, A2, B1: Number of Subjects with Clinically Significant Changes From Baseline in Laboratory Parameters

Primary: Parts A1, A2, B1: Number of Subjects with Clinically Significant Changes From Baseline in Laboratory Parameters

Primary: Parts A1, A2, B1: Number of Subjects with Clinically Significant Changes From Baseline in Vital Signs

Primary: Parts A1, A2, B1: Number of Subjects with Clinically Significant Changes From Baseline in Vital Signs

Primary: Parts A1, A2, B1: Number of Subjects with Clinically Significant Changes From Baseline in 12-Lead Electrocardiograms (ECGs) Findings

Primary: Parts A1, A2, B1: Number of Subjects with Clinically Significant Changes From Baseline in 12-Lead Electrocardiograms (ECGs) Findings

Primary: Part B2: Number of Subjects with Treatment-Emergent Adverse Events (TEAEs)

Primary: Part B2: Number of Subjects with Treatment-Emergent Adverse Events (TEAEs)

Primary: Part B2: Number of Subjects with Clinically Significant Changes from Baseline in Laboratory Parameters

Primary: Part B2: Number of Subjects with Clinically Significant Changes from Baseline in Laboratory Parameters

Primary: Part B2: Number of Subjects with Clinically Significant Changes from Baseline in Vital Signs

Primary: Part B2: Number of Subjects with Clinically Significant Changes from Baseline in Vital Signs

Primary: Part B2: Number of Subjects with Clinically Significant Changes from Baseline in 12-Lead Electrocardiograms (ECGs) Findings

Primary: Part B2: Number of Subjects with Clinically Significant Changes from Baseline in 12-Lead Electrocardiograms (ECGs) Findings

Primary: Parts C1, C2, C3: Number of Subjects with Treatment-Emergent Adverse Events (TEAEs)

Primary: Parts C1, C2, C3: Number of Subjects with Treatment-Emergent Adverse Events (TEAEs)

Primary: Parts C1, C2, C3: Number of Subjects with Clinically Significant Changes from Baseline in Laboratory Parameters

Primary: Parts C1, C2, C3: Number of Subjects with Clinically Significant Changes from Baseline in Laboratory Parameters

Primary: Parts C1, C2, C3: Number of Subjects with Clinically Significant Changes from Baseline in Vital Signs

Primary: Parts C1, C2, C3: Number of Subjects with Clinically Significant Changes from Baseline in Vital Signs

Primary: Parts C1, C2 and C3: Number of Subjects with Clinically Significant Changes from Baseline in 12-Lead Electrocardiograms (ECGs) Findings

Primary: Parts C1, C2 and C3: Number of Subjects with Clinically Significant Changes from Baseline in 12-Lead Electrocardiograms (ECGs) Findings

Primary: Parts C1 and C3: Percentage of Subjects with Objective Response (OR)

Primary: Parts C1 and C3: Percentage of Subjects with Objective Response (OR)

Primary: Part C2: Percentage of Subjects with Objective Response (OR) in Part C2 (TNBC) Who are Basaloid Subtype and BRCA1/BRCA2 Germline wild-type

Primary: Part C2: Percentage of Subjects with Objective Response (OR) in Part C2 (TNBC) Who are Basaloid Subtype and BRCA1/BRCA2 Germline wild-type

Secondary: Parts A1 and A2: Maximum Tolerated Dose (MTD) of M6620

Secondary: Parts A1 and A2: Maximum Tolerated Dose (MTD) of M6620

Secondary: Part A1: Maximum Observed Plasma Concentration (Cmax) of M6620

Secondary: Part A1: Maximum Observed Plasma Concentration (Cmax) of M6620

Secondary: Part A1: Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity (AUC0-inf) of M6620

Secondary: Part A1: Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity (AUC0-inf) of M6620

Secondary: Part A1: Apparent Volume of Distribution at Steady-state (Vss) of M6620

Secondary: Part A1: Apparent Volume of Distribution at Steady-state (Vss) of M6620

Secondary: Part A1: Apparent Total Body Clearance (CL) of M6620

Secondary: Part A1: Apparent Total Body Clearance (CL) of M6620

Secondary: Part A1: Apparent Terminal Half-Life (t1/2) of M6620

Secondary: Part A1: Apparent Terminal Half-Life (t1/2) of M6620

Secondary: Parts A1, A2 and B1: Percentage of Subjects with Objective Tumor Response (OR) as Evaluated by Response Criteria Evaluation in Solid Tumors (RECIST) 1.1

Secondary: Parts A1, A2 and B1: Percentage of Subjects with Objective Tumor Response (OR) as Evaluated by Response Criteria Evaluation in Solid Tumors (RECIST) 1.1

Secondary: Part B1: Maximum Tolerated Dose (MTD) of M6620

Secondary: Part B1: Maximum Tolerated Dose (MTD) of M6620

Secondary: Part B2: Maximum Tolerated Dose (MTD) of M6620

Secondary: Part B2: Maximum Tolerated Dose (MTD) of M6620

Secondary: Part B1: Maximum Observed Plasma Concentration (Cmax) of M6620

Secondary: Part B1: Maximum Observed Plasma Concentration (Cmax) of M6620

Secondary: Part B1: Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity (AUC0-inf) of M6620

Secondary: Part B1: Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity (AUC0-inf) of M6620

Secondary: Part B1: Apparent Volume of Distribution at Steady-state (Vss) of M6620

Secondary: Part B1: Apparent Volume of Distribution at Steady-state (Vss) of M6620

Secondary: Part B1: Apparent Total Body Clearance (CL) of M6620

Secondary: Part B1: Apparent Total Body Clearance (CL) of M6620

Secondary: Part B1: Apparent Terminal Half-Life (t1/2) of M6620

Secondary: Part B1: Apparent Terminal Half-Life (t1/2) of M6620

Secondary: Part B2: Maximum Observed Plasma Concentration (Cmax) of M6620

Secondary: Part B2: Maximum Observed Plasma Concentration (Cmax) of M6620

Secondary: Part B2: Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity (AUC0-inf) of M6620

Secondary: Part B2: Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity (AUC0-inf) of M6620

Secondary: Part B2: Volume of Distribution at Steady-state (Vss) of M6620

Secondary: Part B2: Volume of Distribution at Steady-state (Vss) of M6620

Secondary: Part B2: Apparent Total Body Clearance (CL) of M6620

Secondary: Part B2: Apparent Total Body Clearance (CL) of M6620

Secondary: Part B2: Apparent Terminal Half-Life (t1/2) of M6620

Secondary: Part B2: Apparent Terminal Half-Life (t1/2) of M6620

Secondary: Part B2: Percentage of Subjects with Objective Tumor Response (OR) as Evaluated by Response Criteria Evaluation in Solid Tumors (RECIST) 1.1

Secondary: Part B2: Percentage of Subjects with Objective Tumor Response (OR) as Evaluated by Response Criteria Evaluation in Solid Tumors (RECIST) 1.1

Secondary: Part C2: Percentage of Subjects with Objective Response (OR)

Secondary: Part C2: Percentage of Subjects with Objective Response (OR)

Clinical Trial Results:
An Open-label, First-in-Human Study of the Safety, Tolerability, and Pharmacokinetics of VX-970/M6620 in Combination with Cytotoxic Chemotherapy in Participants With Advanced Solid Tumors