Download PDF

Clinical Trial Results:
A Phase 1/2 Study of Durvalumab and Monalizumab in Adult Subjects with Select Advanced Solid Tumors

Summary
EudraCT number	2016-000662-38
Trial protocol	GB HU ES FR BE IT
Global end of trial date	26 Oct 2021

Results information
Results version number	v2(current)
This version publication date	26 Feb 2023
First version publication date	06 Nov 2022
Other versions	v1
Version creation reason

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

Collapse all Expand all

Trial information

Top of page

Sponsor protocol code

D419NC00001

ISRCTN number

US NCT number

NCT02671435

WHO universal trial number (UTN)

Sponsor organisation name

MedImmune, LLC

Sponsor organisation address

One MedImmune Way, Gaithersburg, Maryland, United States, 20878

Public contact

Global Clinical Lead, AstraZeneca Clinical Study Information Center, +1 877-240-9479, information.center@astrazeneca.com

Scientific contact

Global Clinical Lead, AstraZeneca Clinical Study Information Center, +1 877-240-9479, information.center@astrazeneca.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

22 Dec 2021

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

26 Oct 2021

Was the trial ended prematurely?

Main objective of the trial

1. To assess safety and tolerability, describe dose-limiting toxicities (DLTs), and determine maximum tolerated dose (MTD) of durvalumab in combination with monalizumab in subjects with advanced solid tumors and with select advanced solid tumors. 2. To assess safety and tolerability of durvalumab in combination with monalizumab plus chemotherapy with or without a biologic agent (bevacizumab or cetuximab), in subjects with first line (1L) or second line (2L) MSS-CRC. 3. To assess safety (C1A, C2A) and tolerability (C1A and C2A), and evaluate the preliminary antitumor activity (C1A only) of durvalumab in combination with monalizumab plus cetuximab in subjects with 3L MSS-CRC that is RAS mutant (C1A) or RAS/BRAF wild type (C2A). 4. To assess safety (C1B, C2B) and tolerability (C1B and C2B), and evaluate the preliminary antitumor activity (C1B only) of monalizumab in combination with cetuximab in subjects with 3L MSS-CRC that is RAS mutant (C1B) or RAS/BRAF wild type (C2B).

Protection of trial subjects

The conduct of this clinical study met all local and regulatory requirements. The study was conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki and are consistent with International Conference on Harmonization guideline: Good Clinical Practice, and applicable regulatory requirements. Participants signed an informed consent form and could withdraw from the study at any time without any disadvantage and without having to provide a reason for this decision. Only investigators qualified by training and experience were selected as appropriate experts to investigate the study drug.

Background therapy

Evidence for comparator

Actual start date of recruitment

22 Feb 2016

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

Australia: 3

Country: Number of subjects enrolled

Belgium: 5

Country: Number of subjects enrolled

Canada: 11

Country: Number of subjects enrolled

France: 3

Country: Number of subjects enrolled

Hungary: 8

Country: Number of subjects enrolled

Italy: 9

Country: Number of subjects enrolled

New Zealand: 7

Country: Number of subjects enrolled

Korea, Republic of: 40

Country: Number of subjects enrolled

Spain: 62

Country: Number of subjects enrolled

United Kingdom: 16

Country: Number of subjects enrolled

United States: 219

Worldwide total number of subjects

383

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)

268

From 65 to 84 years

115

85 years and over

Subject disposition

Top of page

Recruitment details

The study was conducted at study sites located in North America, Europe, and Asia Pacific, across 47 sites and 11 countries (Australia, Belgium, Canada, France, Hungary, Italy, New Zealand, South Korea, Spain, United Kingdom, and United States).

Screening details

A total of 383 participants were included in this study of which 382 participants received treatment.

Period 1 title

Overall Study (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Not blinded

Are arms mutually exclusive

Yes

Dose-escalation Cohort 1: Mona 22.5 mg Q2W + Durva

Arm description

Participants received intravenous (IV) infusions of durvalumab (Durva) 1500 mg every 4 weeks (Q4W) in combination with monalizumab (Mona) 22.5 mg every 2 weeks (Q2W) up to 3 years until unacceptable toxicity, documentation of confirmed disease progression (PD), or documentation of subject withdrawal for another reason.

Arm type

Experimental

Investigational medicinal product name

Durvalumab

Investigational medicinal product code

MEDI4736

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Intravenous infusion of durvalumab 1500 mg every 4 weeks (Q4W) up to 3 years until unacceptable toxicity, documentation of confirmed PD, or documentation of subject withdrawal for another reason.

Investigational medicinal product name

Monalizumab

Investigational medicinal product code

IPH2201

Other name

Pharmaceutical forms

Powder for solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Intravenous infusion of monalizumab 22.5 mg every 2 weeks (Q2W) up to 3 years until unacceptable toxicity, documentation of confirmed disease progression (PD), or documentation of subject withdrawal for another reason.

Dose-escalation Cohort 2: Mona 75 mg Q2W + Durva

Arm description

Participants received IV infusions of durvalumab 1500 mg Q4W in combination with monalizumab 75 mg Q2W up to 3 years until unacceptable toxicity, documentation of confirmed PD, or documentation of subject withdrawal for another reason.

Arm type

Experimental

Investigational medicinal product name

Durvalumab

Investigational medicinal product code

MEDI4736

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Intravenous infusion of durvalumab 1500 mg Q4W up to 3 years until unacceptable toxicity, documentation of confirmed PD, or documentation of subject withdrawal for another reason.

Investigational medicinal product name

Monalizumab

Investigational medicinal product code

IPH2201

Other name

Pharmaceutical forms

Powder for solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Intravenous infusion of monalizumab 75 mg Q2W up to 3 years until unacceptable toxicity, documentation of confirmed PD, or documentation of subject withdrawal for another reason.

Dose-escalation Cohort 3: Mona 225 mg Q2W + Durva

Arm description

Participants received IV infusions of durvalumab 1500 mg Q4W in combination with monalizumab 225 mg Q2W up to 3 years until unacceptable toxicity, documentation of confirmed PD, or documentation of subject withdrawal for another reason.

Arm type

Experimental

Investigational medicinal product name

Durvalumab

Investigational medicinal product code

MEDI4736

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Intravenous infusion of durvalumab 1500 mg Q4W up to 3 years until unacceptable toxicity, documentation of confirmed PD, or documentation of subject withdrawal for another reason.

Investigational medicinal product name

Monalizumab

Investigational medicinal product code

IPH2201

Other name

Pharmaceutical forms

Powder for solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Intravenous infusion of monalizumab 225 mg Q2W up to 3 years until unacceptable toxicity, documentation of confirmed PD, or documentation of subject withdrawal for another reason.

Dose-escalation Cohort 4: Mona 750 mg Q2W + Durva

Arm description

Participants received IV infusions of durvalumab 1500 mg Q4W in combination with monalizumab 750 mg Q2W up to 3 years until unacceptable toxicity, documentation of confirmed PD, or documentation of subject withdrawal for another reason.

Arm type

Experimental

Investigational medicinal product name

Durvalumab

Investigational medicinal product code

MEDI4736

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Intravenous infusion of durvalumab 1500 mg Q4W up to 3 years until unacceptable toxicity, documentation of confirmed PD, or documentation of subject withdrawal for another reason.

Investigational medicinal product name

Monalizumab

Investigational medicinal product code

IPH2201

Other name

Pharmaceutical forms

Powder for solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Intravenous infusion of monalizumab 750 mg Q2W up to 3 years until unacceptable toxicity, documentation of confirmed PD, or documentation of subject withdrawal for another reason.

Dose-escalation Cohort 5: Mona 750 mg Q4W + Durva

Arm description

Participants received IV infusions of durvalumab 1500 mg Q4W in combination with monalizumab 750 mg Q4W up to 3 years until unacceptable toxicity, documentation of confirmed PD, or documentation of subject withdrawal for another reason.

Arm type

Experimental

Investigational medicinal product name

Durvalumab

Investigational medicinal product code

MEDI4736

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Intravenous infusion of durvalumab 1500 mg Q4W up to 3 years until unacceptable toxicity, documentation of confirmed PD, or documentation of subject withdrawal for another reason.

Investigational medicinal product name

Monalizumab

Investigational medicinal product code

IPH2201

Other name

Pharmaceutical forms

Powder for solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Intravenous infusion of monalizumab 750 mg Q4W up to 3 years until unacceptable toxicity, documentation of confirmed PD, or documentation of subject withdrawal for another reason.

Dose-expansion Cohort: Mona 750 mg Q2W + Durva (MSS-CRC)

Arm description

Participants with microsatellite-stable colorectal cancer (MSS-CRC) received IV infusions of durvalumab 1500 mg Q4W in combination with monalizumab 750 mg Q2W up to 3 years until unacceptable toxicity, documentation of confirmed PD, or documentation of subject withdrawal for another reason.

Arm type

Experimental

Investigational medicinal product name

Durvalumab

Investigational medicinal product code

MEDI4736

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Intravenous infusion of durvalumab 1500 mg Q4W up to 3 years until unacceptable toxicity, documentation of confirmed PD, or documentation of subject withdrawal for another reason.

Investigational medicinal product name

Monalizumab

Investigational medicinal product code

IPH2201

Other name

Pharmaceutical forms

Powder for solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Intravenous infusion of monalizumab 750 mg Q2W up to 3 years until unacceptable toxicity, documentation of confirmed PD, or documentation of subject withdrawal for another reason.

Dose-expansion Cohort: Mona 750 mg Q2W + Durva (ovarian)

Arm description

Participants with ovarian cancer received IV infusions of durvalumab 1500 mg Q4W in combination with monalizumab 750 mg Q2W up to 3 years until unacceptable toxicity, documentation of confirmed PD, or documentation of subject withdrawal for another reason.

Arm type

Experimental

Investigational medicinal product name

Durvalumab

Investigational medicinal product code

MEDI4736

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Intravenous infusion of durvalumab 1500 mg Q4W up to 3 years until unacceptable toxicity, documentation of confirmed PD, or documentation of subject withdrawal for another reason.

Investigational medicinal product name

Monalizumab

Investigational medicinal product code

IPH2201

Other name

Pharmaceutical forms

Powder for solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Intravenous infusion of monalizumab 750 mg Q2W up to 3 years until unacceptable toxicity, documentation of confirmed PD, or documentation of subject withdrawal for another reason.

Dose-expansion Cohort: Mona 750 mg Q2W+Durva (Endometrial MSS)

Arm description

Participants with endometrial MSS received IV infusions of durvalumab 1500 mg Q4W in combination with monalizumab 750 mg Q2W up to 3 years until unacceptable toxicity, documentation of confirmed PD, or documentation of subject withdrawal for another reason.

Arm type

Experimental

Investigational medicinal product name

Durvalumab

Investigational medicinal product code

MEDI4736

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Intravenous infusion of durvalumab 1500 mg Q4W up to 3 years until unacceptable toxicity, documentation of confirmed PD, or documentation of subject withdrawal for another reason.

Investigational medicinal product name

Monalizumab

Investigational medicinal product code

IPH2201

Other name

Pharmaceutical forms

Powder for solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Intravenous infusion of monalizumab 750 mg Q2W up to 3 years until unacceptable toxicity, documentation of confirmed PD, or documentation of subject withdrawal for another reason.

Dose-expansion Cohort: Mona 750 mg Q2W + Durva (NSCLC)

Arm description

Participants with non-small cell lung cancer (NSCLC) received IV infusions of durvalumab 1500 mg Q4W in combination with monalizumab 750 mg Q2W up to 3 years until unacceptable toxicity, documentation of confirmed PD, or documentation of subject withdrawal for another reason.

Arm type

Experimental

Investigational medicinal product name

Durvalumab

Investigational medicinal product code

MEDI4736

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Intravenous infusion of durvalumab 1500 mg Q4W up to 3 years until unacceptable toxicity, documentation of confirmed PD, or documentation of subject withdrawal for another reason.

Investigational medicinal product name

Monalizumab

Investigational medicinal product code

IPH2201

Other name

Pharmaceutical forms

Powder for solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Intravenous infusion of monalizumab 750 mg Q2W up to 3 years until unacceptable toxicity, documentation of confirmed PD, or documentation of subject withdrawal for another reason.

Exploration Cohort A1: Mona 750 mg Q2W+Durva + mFOLFOX6 + Beva

Arm description

Participants with first-line (1L) MSS-CRC received IV infusions of durvalumab 1500 mg Q4W in combination with monalizumab 750 mg Q2W plus mFOLFOX (oxaliplatin 85 mg/m^2 IV infusion, folinic acid 400 mg/m^2 infusion, fluorouracil 400 mg/m^2 IV bolus, followed by 2400 mg/m^2 continuous IV infusion over 46 to 48 hours on Day 1) Q2W plus IV infusion of bevacizumab (Beva) 5 mg/kg Q2W up to 3 years until unacceptable toxicity, documentation of confirmed PD, or documentation of subject withdrawal for another reason.

Arm type

Experimental

Investigational medicinal product name

Monalizumab

Investigational medicinal product code

IPH2201

Other name

Pharmaceutical forms

Powder for solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Intravenous infusion of monalizumab 750 mg Q2W up to 3 years until unacceptable toxicity, documentation of confirmed PD, or documentation of subject withdrawal for another reason.

Investigational medicinal product name

Bevacizumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Intravenous infusion of bevacizumab 5 mg/kg Q2W up to 3 years until unacceptable toxicity, documentation of confirmed PD, or documentation of subject withdrawal for another reason.

Investigational medicinal product name

mFOLFOX6

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Intravenous infusion of mFOLFOX (oxaliplatin 85 mg/m^2 IV infusion, folinic acid 400 mg/m^2 infusion, fluorouracil 400 mg/m^2 IV bolus, followed by 2400 mg/m^2 continuous IV infusion over 46 to 48 hours on Day 1) Q2W up to 3 years until unacceptable toxicity, documentation of confirmed PD, or documentation of subject withdrawal for another reason.

Investigational medicinal product name

Durvalumab

Investigational medicinal product code

MEDI4736

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Intravenous infusion of durvalumab 1500 mg Q4W up to 3 years until unacceptable toxicity, documentation of confirmed PD, or documentation of subject withdrawal for another reason.

Exploration CohortA2: Mona 750 mg Q2W+Durva+mFOLFOX6+Cetu

Arm description

Participants with 1L MSS-CRC received IV infusions of durvalumab 1500 mg Q4W in combination with monalizumab 750 mg Q2W, plus mFOLFOX6 (oxaliplatin 85 mg/m^2, folinic acid 400 mg/m^2, fluorouracil 400 mg/m^2 IV bolus, followed by 2400 mg/m^2 continuous IV infusion over 46 to 48 hours on Day 1) Q2W plus IV infusion of cetuximab (Cetu) (loading dose of 400 mg/m^2 on Day 1, followed by maintenance dose of 250 mg/m^2 IV infusion every week starting on Day 8, then changed to 500 mg/m^2 IV infusion Q2W) up to 3 years until unacceptable toxicity, documentation of confirmed PD, or documentation of subject withdrawal for another reason.

Arm type

Experimental

Investigational medicinal product name

Monalizumab

Investigational medicinal product code

IPH2201

Other name

Pharmaceutical forms

Powder for solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Intravenous infusion of monalizumab 750 mg Q2W up to 3 years until unacceptable toxicity, documentation of confirmed PD, or documentation of subject withdrawal for another reason.

Investigational medicinal product name

Cetuximab

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Intravenous infusion of cetuximab (loading dose of 400 mg/m^2 on Day 1, followed by maintenance dose of 250 mg/m^2 IV infusion every week starting on Day 8, then changed to 500 mg/m^2 IV infusion Q2W) up to 3 years until unacceptable toxicity, documentation of confirmed PD, or documentation of subject withdrawal for another reason.

Investigational medicinal product name

mFOLFOX6

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Investigational medicinal product name

Durvalumab

Investigational medicinal product code

MEDI4736

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Intravenous infusion of durvalumab 1500 mg Q4W up to 3 years until unacceptable toxicity, documentation of confirmed PD, or documentation of subject withdrawal for another reason.

Exploration Cohort C1A: Mona 750 mg Q2W + Durva + Cetu

Arm description

Participants with recurrent or metastatic third-line (3L) RAS mutant MSS-CRC received IV infusions of durvalumab 1500 mg Q4W in combination with monalizumab 750 mg Q2W plus IV infusion of cetuximab 500 mg/m^2 on Day 1 then 500 mg/m^2 IV infusion Q2W starting on Day 15 up to 3 years until unacceptable toxicity, documentation of confirmed PD, or documentation of subject withdrawal for another reason.

Arm type

Experimental

Investigational medicinal product name

Monalizumab

Investigational medicinal product code

IPH2201

Other name

Pharmaceutical forms

Powder for solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Intravenous infusion of monalizumab 750 mg Q2W up to 3 years until unacceptable toxicity, documentation of confirmed PD, or documentation of subject withdrawal for another reason.

Investigational medicinal product name

Cetuximab

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Intravenous infusion of cetuximab 500 mg/m^2 on Day 1 then 500 mg/m^2 IV infusion Q2W starting on Day 15 up to 3 years until unacceptable toxicity, documentation of confirmed PD, or documentation of subject withdrawal for another reason.

Investigational medicinal product name

Durvalumab

Investigational medicinal product code

MEDI4736

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Intravenous infusion of durvalumab 1500 mg Q4W up to 3 years until unacceptable toxicity, documentation of confirmed PD, or documentation of subject withdrawal for another reason.

Exploration Cohort C1B: Mona 750 mg Q2W + Cetu

Arm description

Participants with recurrent or metastatic 3L RAS mutant MSS-CRC received IV infusion of monalizumab 750 mg Q2W plus IV infusion of cetuximab 500 mg/m^2 on Day 1 then 500 mg/m^2 IV infusion Q2W starting on Day 15 up to 3 years until unacceptable toxicity, documentation of confirmed PD, or documentation of subject withdrawal for another reason.

Arm type

Experimental

Investigational medicinal product name

Cetuximab

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Investigational medicinal product name

Monalizumab

Investigational medicinal product code

IPH2201

Other name

Pharmaceutical forms

Powder for solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Intravenous infusion of monalizumab 750 mg Q2W up to 3 years until unacceptable toxicity, documentation of confirmed PD, or documentation of subject withdrawal for another reason.

Exploration Cohort C2A: Mona 750 mg Q2W + Durva + Cetu

Arm description

Participants with recurrent or metastatic 3L RAS/BRAF wild type MSS-CRC received IV infusions of durvalumab 1500 mg Q4W in combination with monalizumab 750 mg Q2W plus IV infusion of cetuximab 500 mg/m^2 on Day 1 then 500 mg/m^2 IV infusion Q2W starting on Day 15 up to 3 years until unacceptable toxicity, documentation of confirmed PD, or documentation of subject withdrawal for another reason.

Arm type

Experimental

Investigational medicinal product name

Monalizumab

Investigational medicinal product code

IPH2201

Other name

Pharmaceutical forms

Powder for solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Intravenous infusion of monalizumab 750 mg Q2W up to 3 years until unacceptable toxicity, documentation of confirmed PD, or documentation of subject withdrawal for another reason.

Investigational medicinal product name

Cetuximab

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Investigational medicinal product name

Durvalumab

Investigational medicinal product code

MEDI4736

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Intravenous infusion of durvalumab 1500 mg Q4W up to 3 years until unacceptable toxicity, documentation of confirmed PD, or documentation of subject withdrawal for another reason.

Exploration Cohort C2B: Mona 750 mg Q2W + Cetu

Arm description

Participants with recurrent or metastatic 3L RAS/BRAF wild type MSS-CRC received IV infusion of monalizumab 750 mg Q2W plus IV infusion of cetuximab 500 mg/m^2 on Day 1 then 500 mg/m^2 IV infusion Q2W starting on Day 15 up to 3 years until unacceptable toxicity, documentation of confirmed PD, or documentation of subject withdrawal for another reason.

Arm type

Experimental

Investigational medicinal product name

Cetuximab

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Investigational medicinal product name

Monalizumab

Investigational medicinal product code

IPH2201

Other name

Pharmaceutical forms

Powder for solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Intravenous infusion of monalizumab 750 mg Q2W up to 3 years until unacceptable toxicity, documentation of confirmed PD, or documentation of subject withdrawal for another reason.

Number of subjects in period 1	Dose-escalation Cohort 1: Mona 22.5 mg Q2W + Durva	Dose-escalation Cohort 2: Mona 75 mg Q2W + Durva	Dose-escalation Cohort 3: Mona 225 mg Q2W + Durva	Dose-escalation Cohort 4: Mona 750 mg Q2W + Durva	Dose-escalation Cohort 5: Mona 750 mg Q4W + Durva	Dose-expansion Cohort: Mona 750 mg Q2W + Durva (MSS-CRC)	Dose-expansion Cohort: Mona 750 mg Q2W + Durva (ovarian)	Dose-expansion Cohort: Mona 750 mg Q2W+Durva (Endometrial MSS)	Dose-expansion Cohort: Mona 750 mg Q2W + Durva (NSCLC)	Exploration Cohort A1: Mona 750 mg Q2W+Durva + mFOLFOX6 + Beva	Exploration CohortA2: Mona 750 mg Q2W+Durva+mFOLFOX6+Cetu	Exploration Cohort C1A: Mona 750 mg Q2W + Durva + Cetu	Exploration Cohort C1B: Mona 750 mg Q2W + Cetu	Exploration Cohort C2A: Mona 750 mg Q2W + Durva + Cetu	Exploration Cohort C2B: Mona 750 mg Q2W + Cetu
Started	3	3	3	18	18	40	40	40	20	18	18	40	41	44	37
Treated	3	3	3	18	18	40	40	40	20	18	18	39	41	44	37
Completed	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Not completed	3	3	3	18	18	40	40	40	20	18	18	40	41	44	37
Adverse event, serious fatal	-	-	-	1	-	-	-	2	1	-	-	-	-	-	1
Consent withdrawn by subject	2	-	2	2	2	7	2	7	1	1	2	4	4	4	2
Death	1	3	-	15	14	29	34	26	18	10	8	29	29	29	26
Un-specified	-	-	-	-	1	3	2	3	-	5	8	4	5	9	8
Lost to follow-up	-	-	1	-	1	1	2	2	-	2	-	3	3	2	-

Baseline characteristics

Top of page

Reporting group title

Dose-escalation Cohort 1: Mona 22.5 mg Q2W + Durva

Reporting group description

Reporting group title

Dose-escalation Cohort 2: Mona 75 mg Q2W + Durva

Reporting group description

Reporting group title

Dose-escalation Cohort 3: Mona 225 mg Q2W + Durva

Reporting group description

Reporting group title

Dose-escalation Cohort 4: Mona 750 mg Q2W + Durva

Reporting group description

Reporting group title

Dose-escalation Cohort 5: Mona 750 mg Q4W + Durva

Reporting group description

Reporting group title

Dose-expansion Cohort: Mona 750 mg Q2W + Durva (MSS-CRC)

Reporting group description

Reporting group title

Dose-expansion Cohort: Mona 750 mg Q2W + Durva (ovarian)

Reporting group description

Reporting group title

Dose-expansion Cohort: Mona 750 mg Q2W+Durva (Endometrial MSS)

Reporting group description

Reporting group title

Dose-expansion Cohort: Mona 750 mg Q2W + Durva (NSCLC)

Reporting group description

Reporting group title

Exploration Cohort A1: Mona 750 mg Q2W+Durva + mFOLFOX6 + Beva

Reporting group description

Reporting group title

Exploration CohortA2: Mona 750 mg Q2W+Durva+mFOLFOX6+Cetu

Reporting group description

Reporting group title

Exploration Cohort C1A: Mona 750 mg Q2W + Durva + Cetu

Reporting group description

Reporting group title

Exploration Cohort C1B: Mona 750 mg Q2W + Cetu

Reporting group description

Reporting group title

Exploration Cohort C2A: Mona 750 mg Q2W + Durva + Cetu

Reporting group description

Reporting group title

Exploration Cohort C2B: Mona 750 mg Q2W + Cetu

Reporting group description

Reporting group values	Dose-escalation Cohort 1: Mona 22.5 mg Q2W + Durva	Dose-escalation Cohort 2: Mona 75 mg Q2W + Durva	Dose-escalation Cohort 3: Mona 225 mg Q2W + Durva	Dose-escalation Cohort 4: Mona 750 mg Q2W + Durva	Dose-escalation Cohort 5: Mona 750 mg Q4W + Durva	Dose-expansion Cohort: Mona 750 mg Q2W + Durva (MSS-CRC)	Dose-expansion Cohort: Mona 750 mg Q2W + Durva (ovarian)	Dose-expansion Cohort: Mona 750 mg Q2W+Durva (Endometrial MSS)	Dose-expansion Cohort: Mona 750 mg Q2W + Durva (NSCLC)	Exploration Cohort A1: Mona 750 mg Q2W+Durva + mFOLFOX6 + Beva	Exploration CohortA2: Mona 750 mg Q2W+Durva+mFOLFOX6+Cetu	Exploration Cohort C1A: Mona 750 mg Q2W + Durva + Cetu	Exploration Cohort C1B: Mona 750 mg Q2W + Cetu	Exploration Cohort C2A: Mona 750 mg Q2W + Durva + Cetu	Exploration Cohort C2B: Mona 750 mg Q2W + Cetu	Total
Number of subjects	3	3	3	18	18	40	40	40	20	18	18	40	41	44	37	383
Age Categorical
Intent-to-treat (ITT) population included participants who were randomized and were analyzed according to the treatment group they were randomized to.
Units: Participants
<=18 years	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Between 18 and 65 years	1	2	2	14	10	33	24	21	9	10	15	31	36	33	27	268
>=65 years	2	1	1	4	8	7	16	19	11	8	3	9	5	11	10	115
Age continuous
The ITT population included participants who were randomized and were analyzed according to the treatment group they were randomized to.
Units: years
arithmetic mean (standard deviation)	58.0 ± 21.7	55.7 ± 18.0	59 ± 15.1	56.4 ± 13.5	60 ± 13.5	53.6 ± 12.9	61.5 ± 9.1	63.7 ± 8.1	63.2 ± 7.9	60.8 ± 9.9	55.4 ± 9.4	55.8 ± 10.7	52.3 ± 10.6	55.9 ± 11.3	58.8 ± 9.6	-
Sex: Female, Male
The ITT population included participants who were randomized and were analyzed according to the treatment group they were randomized to.
Units: Participants
Female	3	3	2	17	6	15	40	40	6	8	8	17	16	17	18	216
Male	0	0	1	1	12	25	0	0	14	10	10	23	25	27	19	167
Race (NIH/OMB)
The ITT population included participants who were randomized and were analyzed according to the treatment group they were randomized to.
Units: Subjects
American Indian or Alaska Native	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	1
Asian	0	0	0	1	2	3	1	2	0	1	4	9	8	14	13	58
Native Hawaiian or Other Pacific Islander	0	0	0	1	0	0	0	0	1	0	0	0	0	1	0	3
Black or African American	0	0	0	1	0	1	3	4	1	2	0	2	1	1	1	17
White	3	3	3	15	15	36	35	30	16	13	13	29	30	25	22	288
More than one race	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	1
Unknown or Not Reported	0	0	0	0	1	0	1	3	2	2	1	0	2	2	1	15
Ethnicity (NIH/OMB)
The ITT population included participants who were randomized and were analyzed according to the treatment group they were randomized to.
Units: Subjects
Hispanic or Latino	1	1	0	3	0	6	5	3	2	1	1	3	6	4	0	36
Not Hispanic or Latino	2	2	3	15	17	34	35	37	16	17	17	37	35	40	37	344
Unknown or Not Reported	0	0	0	0	1	0	0	0	2	0	0	0	0	0	0	3

End points

Top of page

Reporting group title

Dose-escalation Cohort 1: Mona 22.5 mg Q2W + Durva

Reporting group description

Reporting group title

Dose-escalation Cohort 2: Mona 75 mg Q2W + Durva

Reporting group description

Reporting group title

Dose-escalation Cohort 3: Mona 225 mg Q2W + Durva

Reporting group description

Reporting group title

Dose-escalation Cohort 4: Mona 750 mg Q2W + Durva

Reporting group description

Reporting group title

Dose-escalation Cohort 5: Mona 750 mg Q4W + Durva

Reporting group description

Reporting group title

Dose-expansion Cohort: Mona 750 mg Q2W + Durva (MSS-CRC)

Reporting group description

Reporting group title

Dose-expansion Cohort: Mona 750 mg Q2W + Durva (ovarian)

Reporting group description

Reporting group title

Dose-expansion Cohort: Mona 750 mg Q2W+Durva (Endometrial MSS)

Reporting group description

Reporting group title

Dose-expansion Cohort: Mona 750 mg Q2W + Durva (NSCLC)

Reporting group description

Reporting group title

Exploration Cohort A1: Mona 750 mg Q2W+Durva + mFOLFOX6 + Beva

Reporting group description

Reporting group title

Exploration CohortA2: Mona 750 mg Q2W+Durva+mFOLFOX6+Cetu

Reporting group description

Reporting group title

Exploration Cohort C1A: Mona 750 mg Q2W + Durva + Cetu

Reporting group description

Reporting group title

Exploration Cohort C1B: Mona 750 mg Q2W + Cetu

Reporting group description

Reporting group title

Exploration Cohort C2A: Mona 750 mg Q2W + Durva + Cetu

Reporting group description

Reporting group title

Exploration Cohort C2B: Mona 750 mg Q2W + Cetu

Reporting group description

Subject analysis set title

Dose-escalation Cohort4+Dose-expansion: Mona 750mg Q2W + Durva

Subject analysis set type

Sub-group analysis

Subject analysis set description

Participants with solid tumors, microsatellite-stable colorectal cancer (MSS-CRC), ovarian cancer, MSS endometrial cancer or non-small cell lung cancer (NSCLC) received IV infusions of durvalumab 1500 mg Q4W in combination with monalizumab 750 mg Q2W up to 3 years until unacceptable toxicity, documentation of confirmed PD, or documentation of subject withdrawal for another reason.

Subject analysis set title

Dose-escalation (1-5) + dose-expansion + dose-exploration

Subject analysis set type

Sub-group analysis

Subject analysis set description

Participants in dose-escalation cohorts received IV infusions of durvalumab 1500 mg Q4W in combination with monalizumab 22.5, 75, 225 or 750 mg Q2W (Cohorts 1, 2, 3 and 4) or 750 mg Q4W (Cohort 5), dose-expansion cohorts participants received IV infusions of durvalumab 1500 mg Q4W in combination with monalizumab 750 mg Q2W. Participants with recurrent or metastatic 3L RAS mutant (C1A) or RAS/BRAF wild type (C2A) MSS-CRC received IV infusions of durvalumab 1500 mg Q4W in combination with monalizumab 750 mg Q2W plus IV infusion of cetuximab. Participants with 1L MSS-CRC in Cohorts A1 and A2 received IV infusions of durvalumab 1500 mg Q4W in combination with monalizumab 750 mg Q2W, plus mFOLFOX6 Q2W plus either IV infusion of bevacizumab 5 mg/kg Q2W (Cohort A1) or IV infusion of cetuximab (Cohort A2). Participants in all cohorts received treatment up to 3 years until unacceptable toxicity, documentation of confirmed PD, or documentation of subject withdrawal for another reason.

Subject analysis set title

Exploration Cohorts A2, C1A, C2A, C1B, and C2B

Subject analysis set type

Sub-group analysis

Subject analysis set description

Participants with recurrent or metastatic 3L RAS mutant (C1A) or RAS/BRAF wild type (C2A) MSS-CRC received IV infusions of durvalumab 1500 mg Q4W in combination with monalizumab 750 mg Q2W plus IV infusion of cetuximab 500 mg/m^2 on Day 1 then 500 mg/m^2 IV infusion Q2W starting on Day 15. Participants with recurrent or metastatic 3L RAS mutant (C1B) or RAS/BRAF wild type (C2B) MSS-CRC received IV infusions monalizumab 750 mg Q2W plus IV infusion of cetuximab 500 mg/m^2 on Day 1 then 500 mg/m^2 IV infusion Q2W starting on Day 15. Participants with 1L MSS-CRC in Cohort A2 received IV infusions of durvalumab 1500 mg Q4W in combination with monalizumab 750 mg Q2W, plus mFOLFOX6 Q2W plus IV infusion of cetuximab (Cohort A2). Participants in all cohorts received treatment up to 3 years until unacceptable toxicity, documentation of confirmed PD, or documentation of subject withdrawal for another reason.

Primary: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)

Top of page

End point title

Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) ^[1]

End point description

An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. The TEAEs are defined as events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug. As-treated population included participants who received any study drugs and were analyzed according to the treatment they actually received. Any TEAEs data is inclusive of both serious and other adverse events (non-serious).

End point type

Primary

End point timeframe

Day 1 through 246.9 weeks (maximum observed duration)

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: Statistical analysis was not applicable since there were no inferential statistics, only descriptive statistics were performed for this end point.

End point values	Dose-escalation Cohort 1: Mona 22.5 mg Q2W + Durva	Dose-escalation Cohort 2: Mona 75 mg Q2W + Durva	Dose-escalation Cohort 3: Mona 225 mg Q2W + Durva	Dose-escalation Cohort 4: Mona 750 mg Q2W + Durva	Dose-escalation Cohort 5: Mona 750 mg Q4W + Durva	Dose-expansion Cohort: Mona 750 mg Q2W + Durva (MSS-CRC)	Dose-expansion Cohort: Mona 750 mg Q2W + Durva (ovarian)	Dose-expansion Cohort: Mona 750 mg Q2W+Durva (Endometrial MSS)	Dose-expansion Cohort: Mona 750 mg Q2W + Durva (NSCLC)	Exploration Cohort A1: Mona 750 mg Q2W+Durva + mFOLFOX6 + Beva	Exploration CohortA2: Mona 750 mg Q2W+Durva+mFOLFOX6+Cetu	Exploration Cohort C1A: Mona 750 mg Q2W + Durva + Cetu	Exploration Cohort C1B: Mona 750 mg Q2W + Cetu	Exploration Cohort C2A: Mona 750 mg Q2W + Durva + Cetu	Exploration Cohort C2B: Mona 750 mg Q2W + Cetu
Number of subjects analysed	3	3	3	18	18	40	40	40	20	18	18	39	41	44	37
Units: Participants
Any TEAEs	3	3	3	18	17	39	40	39	20	18	18	39	41	44	36
Any TESAEs	1	0	1	8	4	11	16	17	7	10	11	10	5	9	11

No statistical analyses for this end point

Primary: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)

Top of page

End point title

Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) ^[2]

End point description

Change from baseline in SBP and DBP (minimum post baseline change [PBC] and maximum PBC) are reported. As-treated population included participants who received any study drugs and were analyzed according to the treatment they actually received.

End point type

Primary

End point timeframe

Day 1 (baseline) through 246.9 weeks (maximum observed duration)

Notes
[2] - 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: Statistical analysis was not applicable since there were no inferential statistics, only descriptive statistics were performed for this end point.

Dose-escalation Cohort 1: Mona 22.5 mg Q2W + Durva

Dose-escalation Cohort 2: Mona 75 mg Q2W + Durva

Dose-escalation Cohort 3: Mona 225 mg Q2W + Durva

Dose-escalation Cohort 4: Mona 750 mg Q2W + Durva

Dose-escalation Cohort 5: Mona 750 mg Q4W + Durva

Dose-expansion Cohort: Mona 750 mg Q2W + Durva (MSS-CRC)

Dose-expansion Cohort: Mona 750 mg Q2W + Durva (ovarian)

Dose-expansion Cohort: Mona 750 mg Q2W+Durva (Endometrial MSS)

Dose-expansion Cohort: Mona 750 mg Q2W + Durva (NSCLC)

Exploration Cohort A1: Mona 750 mg Q2W+Durva + mFOLFOX6 + Beva

Exploration CohortA2: Mona 750 mg Q2W+Durva+mFOLFOX6+Cetu

Exploration Cohort C1A: Mona 750 mg Q2W + Durva + Cetu

Exploration Cohort C1B: Mona 750 mg Q2W + Cetu

Exploration Cohort C2A: Mona 750 mg Q2W + Durva + Cetu

Exploration Cohort C2B: Mona 750 mg Q2W + Cetu

Number of subjects analysed

Units: mmHg

arithmetic mean (standard deviation)

SBP min PBC

-19.00 ± 21.63

-26.00 ± 10.82

-14.67 ± 11.55

-22.94 ± 12.73

-23.06 ± 20.48

-21.45 ± 12.89

-22.55 ± 13.35

-21.23 ± 12.29

-26.40 ± 12.75

-29.28 ± 19.19

-24.61 ± 10.92

-23.31 ± 12.88

-20.80 ± 11.87

-25.57 ± 13.99

-25.05 ± 16.86

SBP max PBC

27.33 ± 5.69

19.00 ± 5.57

28.67 ± 20.82

29.22 ± 15.78

22.00 ± 19.16

21.10 ± 12.04

22.15 ± 17.39

23.55 ± 14.13

22.95 ± 11.69

27.17 ± 21.63

23.61 ± 11.27

20.74 ± 15.31

17.20 ± 10.51

23.00 ± 13.18

22.59 ± 15.69

DBP min PBC

-15.67 ± 18.01

-22.00 ± 10.00

-10.67 ± 9.07

-17.89 ± 9.58

-18.61 ± 11.05

-16.60 ± 10.40

-17.60 ± 9.81

-13.05 ± 7.21

-19.15 ± 10.28

-18.11 ± 8.98

-20.50 ± 9.79

-16.13 ± 9.33

-16.39 ± 9.94

-18.09 ± 9.69

-17.68 ± 12.15

DBP max PBC

23.67 ± 11.93

11.67 ± 4.93

18.00 ± 9.64

14.06 ± 12.75

12.39 ± 9.30

15.58 ± 9.69

12.63 ± 11.11

19.83 ± 10.15

16.65 ± 9.46

18.11 ± 9.33

14.22 ± 12.18

13.54 ± 10.01

13.10 ± 8.98

16.05 ± 10.06

14.43 ± 9.01

No statistical analyses for this end point

Primary: Change From Baseline in Respiratory Rate (RR)

Top of page

End point title

Change From Baseline in Respiratory Rate (RR) ^[3]

End point description

Change from baseline in RR (minimum PBC and maximum PBC) are reported. As-treated population included participants who received any study drugs and were analyzed according to the treatment they actually received.

End point type

Primary

End point timeframe

Day 1 (baseline) through 246.9 weeks (maximum observed duration)

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: Statistical analysis was not applicable since there were no inferential statistics, only descriptive statistics were performed for this end point.

Dose-escalation Cohort 1: Mona 22.5 mg Q2W + Durva

Dose-escalation Cohort 2: Mona 75 mg Q2W + Durva

Dose-escalation Cohort 3: Mona 225 mg Q2W + Durva

Dose-escalation Cohort 4: Mona 750 mg Q2W + Durva

Dose-escalation Cohort 5: Mona 750 mg Q4W + Durva

Dose-expansion Cohort: Mona 750 mg Q2W + Durva (MSS-CRC)

Dose-expansion Cohort: Mona 750 mg Q2W + Durva (ovarian)

Dose-expansion Cohort: Mona 750 mg Q2W+Durva (Endometrial MSS)

Dose-expansion Cohort: Mona 750 mg Q2W + Durva (NSCLC)

Exploration Cohort A1: Mona 750 mg Q2W+Durva + mFOLFOX6 + Beva

Exploration CohortA2: Mona 750 mg Q2W+Durva+mFOLFOX6+Cetu

Exploration Cohort C1A: Mona 750 mg Q2W + Durva + Cetu

Exploration Cohort C1B: Mona 750 mg Q2W + Cetu

Exploration Cohort C2A: Mona 750 mg Q2W + Durva + Cetu

Exploration Cohort C2B: Mona 750 mg Q2W + Cetu

Number of subjects analysed

Units: breaths/min

arithmetic mean (standard deviation)

RR min PBC

-2.00 ± 2.00

-3.00 ± 1.00

-1.33 ± 2.31

-1.78 ± 1.31

-1.50 ± 1.86

-1.93 ± 1.86

-1.53 ± 1.52

-1.83 ± 1.62

-1.55 ± 3.12

-2.00 ± 1.94

-1.67 ± 1.78

-2.15 ± 2.23

-1.59 ± 1.52

-2.00 ± 1.33

-1.92 ± 1.89

RR max PBC

2.00 ± 3.46

2.33 ± 0.58

2.67 ± 1.15

1.72 ± 1.49

1.83 ± 1.42

2.40 ± 2.37

2.53 ± 2.24

2.40 ± 2.62

4.05 ± 3.09

2.50 ± 2.09

3.39 ± 3.62

1.85 ± 1.73

2.00 ± 1.55

2.59 ± 1.83

3.14 ± 4.60

No statistical analyses for this end point

Primary: Change From Baseline in Pulse Rate (PR)

Top of page

End point title

Change From Baseline in Pulse Rate (PR) ^[4]

End point description

Change from baseline in PR (minimum PBC and maximum PBC) are reported. As-treated population included participants who received any study drugs and were analyzed according to the treatment they actually received.

End point type

Primary

End point timeframe

Day 1 (baseline) through 246.9 weeks (maximum observed duration)

Notes
[4] - 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: Statistical analysis was not applicable since there were no inferential statistics, only descriptive statistics were performed for this end point.

Dose-escalation Cohort 1: Mona 22.5 mg Q2W + Durva

Dose-escalation Cohort 2: Mona 75 mg Q2W + Durva

Dose-escalation Cohort 3: Mona 225 mg Q2W + Durva

Dose-escalation Cohort 4: Mona 750 mg Q2W + Durva

Dose-escalation Cohort 5: Mona 750 mg Q4W + Durva

Dose-expansion Cohort: Mona 750 mg Q2W + Durva (MSS-CRC)

Dose-expansion Cohort: Mona 750 mg Q2W + Durva (ovarian)

Dose-expansion Cohort: Mona 750 mg Q2W+Durva (Endometrial MSS)

Dose-expansion Cohort: Mona 750 mg Q2W + Durva (NSCLC)

Exploration Cohort A1: Mona 750 mg Q2W+Durva + mFOLFOX6 + Beva

Exploration CohortA2: Mona 750 mg Q2W+Durva+mFOLFOX6+Cetu

Exploration Cohort C1A: Mona 750 mg Q2W + Durva + Cetu

Exploration Cohort C1B: Mona 750 mg Q2W + Cetu

Exploration Cohort C2A: Mona 750 mg Q2W + Durva + Cetu

Exploration Cohort C2B: Mona 750 mg Q2W + Cetu

Number of subjects analysed

Units: beats/min

arithmetic mean (standard deviation)

PR min PBC

-5.33 ± 2.52

-14.33 ± 6.51

-7.00 ± 1.73

-15.67 ± 11.83

-15.39 ± 9.20

-14.70 ± 9.39

-12.24 ± 10.10

-11.38 ± 10.98

-13.95 ± 9.12

-15.67 ± 8.84

-18.11 ± 11.98

-15.74 ± 11.20

-13.15 ± 11.89

-13.91 ± 7.04

-11.68 ± 9.02

PR max PBC

38.33 ± 10.02

16.67 ± 6.11

21.67 ± 8.08

19.33 ± 15.05

17.78 ± 11.12

20.28 ± 10.03

20.68 ± 13.42

22.60 ± 12.17

25.80 ± 11.27

21.28 ± 13.48

21.06 ± 12.24

23.54 ± 12.83

23.88 ± 11.31

25.18 ± 13.71

27.38 ± 13.92

No statistical analyses for this end point

Primary: Change From Baseline in Body Temperature (BT)

Top of page

End point title

Change From Baseline in Body Temperature (BT) ^[5]

End point description

Change from baseline in BT (minimum PBC and maximum PBC) are reported. As-treated population included participants who received any study drugs and were analyzed according to the treatment they actually received.

End point type

Primary

End point timeframe

Day 1 (baseline) through 246.9 weeks (maximum observed duration)

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: Statistical analysis was not applicable since there were no inferential statistics, only descriptive statistics were performed for this end point.

Dose-escalation Cohort 1: Mona 22.5 mg Q2W + Durva

Dose-escalation Cohort 2: Mona 75 mg Q2W + Durva

Dose-escalation Cohort 3: Mona 225 mg Q2W + Durva

Dose-escalation Cohort 4: Mona 750 mg Q2W + Durva

Dose-escalation Cohort 5: Mona 750 mg Q4W + Durva

Dose-expansion Cohort: Mona 750 mg Q2W + Durva (MSS-CRC)

Dose-expansion Cohort: Mona 750 mg Q2W + Durva (ovarian)

Dose-expansion Cohort: Mona 750 mg Q2W+Durva (Endometrial MSS)

Dose-expansion Cohort: Mona 750 mg Q2W + Durva (NSCLC)

Exploration Cohort A1: Mona 750 mg Q2W+Durva + mFOLFOX6 + Beva

Exploration CohortA2: Mona 750 mg Q2W+Durva+mFOLFOX6+Cetu

Exploration Cohort C1A: Mona 750 mg Q2W + Durva + Cetu

Exploration Cohort C1B: Mona 750 mg Q2W + Cetu

Exploration Cohort C2A: Mona 750 mg Q2W + Durva + Cetu

Exploration Cohort C2B: Mona 750 mg Q2W + Cetu

Number of subjects analysed

Units: degree Celsius

arithmetic mean (standard deviation)

BT min PBC

-0.30 ± 0.30

-0.37 ± 0.38

-0.67 ± 0.55

-0.66 ± 0.56

-0.48 ± 0.28

-0.62 ± 0.39

-0.63 ± 0.42

-0.47 ± 0.32

-0.51 ± 0.26

-0.84 ± 0.46

-0.79 ± 0.48

-0.51 ± 0.39

-0.52 ± 0.33

-0.65 ± 0.45

-0.66 ± 0.58

BT max PBC

0.63 ± 0.32

0.93 ± 0.92

0.50 ± 0.26

0.78 ± 0.72

0.60 ± 0.73

0.65 ± 0.43

0.64 ± 0.46

0.77 ± 0.47

0.72 ± 0.46

0.89 ± 0.51

0.56 ± 0.43

0.75 ± 0.57

0.70 ± 0.53

0.91 ± 0.64

0.81 ± 0.66

No statistical analyses for this end point

Primary: Change From Baseline in Oxygen Saturation (OS)

Top of page

End point title

Change From Baseline in Oxygen Saturation (OS) ^[6]

End point description

Change from baseline in OS (minimum PBC and maximum PBC) are reported. The arbitrary number 99999 signified standard deviation was not reported as only one participant was evaluable for the specified arm group. As-treated population included participants who received any study drugs and were analyzed according to the treatment they actually received.

End point type

Primary

End point timeframe

Day 1 (baseline) through 246.9 weeks (maximum observed duration)

Notes
[6] - 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: Statistical analysis was not applicable since there were no inferential statistics, only descriptive statistics were performed for this end point.

Dose-escalation Cohort 1: Mona 22.5 mg Q2W + Durva

Dose-escalation Cohort 2: Mona 75 mg Q2W + Durva

Dose-escalation Cohort 3: Mona 225 mg Q2W + Durva

Dose-escalation Cohort 4: Mona 750 mg Q2W + Durva

Dose-escalation Cohort 5: Mona 750 mg Q4W + Durva

Dose-expansion Cohort: Mona 750 mg Q2W + Durva (MSS-CRC)

Dose-expansion Cohort: Mona 750 mg Q2W + Durva (ovarian)

Dose-expansion Cohort: Mona 750 mg Q2W+Durva (Endometrial MSS)

Dose-expansion Cohort: Mona 750 mg Q2W + Durva (NSCLC)

Exploration Cohort A1: Mona 750 mg Q2W+Durva + mFOLFOX6 + Beva

Exploration CohortA2: Mona 750 mg Q2W+Durva+mFOLFOX6+Cetu

Exploration Cohort C1A: Mona 750 mg Q2W + Durva + Cetu

Exploration Cohort C1B: Mona 750 mg Q2W + Cetu

Exploration Cohort C2A: Mona 750 mg Q2W + Durva + Cetu

Exploration Cohort C2B: Mona 750 mg Q2W + Cetu

Number of subjects analysed

0 ^[7]

0 ^[8]

0 ^[9]

0 ^[10]

Units: Percentage of oxygen saturation

arithmetic mean (standard deviation)

OS min PBC

-1.00 ± 99999

-3.00 ± 99999

-0.67 ± 1.53

-21.00 ± 99999

0 ± 99999

0.50 ± 2.12

-4.00 ± 99999

0.50 ± 0.71

-1.00 ± 99999

-0.33 ± 2.80

OS max PBC

-1.00 ± 99999

-3.00 ± 99999

-0.67 ± 1.53

-21.00 ± 99999

0 ± 99999

0.50 ± 2.12

-4.00 ± 99999

0.50 ± 0.71

-1.00 ± 99999

-0.33 ± 2.80

Notes
[7] - No participants were analyzed for change in OS.
[8] - No participants were analyzed for change in OS.
[9] - No participants were analyzed for change in OS.
[10] - No participants were analyzed for change in OS.

No statistical analyses for this end point

Primary: Number of Participants With Notable Change in QTcF and QTcB From Baseline

Top of page

End point title

Number of Participants With Notable Change in QTcF and QTcB From Baseline ^[11]

End point description

Participants who had notable QTcF and QTcB interval change from baseline are reported. As-treated population included participants who received any study drugs and were analyzed according to the treatment they actually received.

End point type

Primary

End point timeframe

Day 1 (baseline) through 246.9 weeks (maximum observed duration)

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 those baseline period arms for which analysis was planned were reported in the end point.

End point values	Dose-escalation Cohort 1: Mona 22.5 mg Q2W + Durva	Dose-escalation Cohort 2: Mona 75 mg Q2W + Durva	Dose-escalation Cohort 3: Mona 225 mg Q2W + Durva	Dose-escalation Cohort 4: Mona 750 mg Q2W + Durva	Dose-escalation Cohort 5: Mona 750 mg Q4W + Durva	Dose-expansion Cohort: Mona 750 mg Q2W + Durva (MSS-CRC)	Dose-expansion Cohort: Mona 750 mg Q2W + Durva (ovarian)	Dose-expansion Cohort: Mona 750 mg Q2W+Durva (Endometrial MSS)	Dose-expansion Cohort: Mona 750 mg Q2W + Durva (NSCLC)	Exploration Cohort A1: Mona 750 mg Q2W+Durva + mFOLFOX6 + Beva	Exploration CohortA2: Mona 750 mg Q2W+Durva+mFOLFOX6+Cetu	Exploration Cohort C1A: Mona 750 mg Q2W + Durva + Cetu	Exploration Cohort C1B: Mona 750 mg Q2W + Cetu	Exploration Cohort C2A: Mona 750 mg Q2W + Durva + Cetu	Exploration Cohort C2B: Mona 750 mg Q2W + Cetu
Number of subjects analysed	3	3	3	16	18	39	38	40	19	18	17	39	40	43	37
Units: Participants
QTcF>30 msec	0	0	0	2	1	6	5	2	2	1	2	3	3	5	5
QTcF>60 msec	0	0	0	1	0	0	2	1	1	0	0	1	1	0	1
QTcB>30 msec	1	0	0	3	2	5	5	4	3	1	6	4	8	9	6
QTcB>60 msec	0	0	0	1	0	1	3	1	1	0	0	1	2	0	1

No statistical analyses for this end point

Primary: Number of Participants With at Least 2-Grade Shift From Baseline in Laboratory Parameters

Top of page

End point title

Number of Participants With at Least 2-Grade Shift From Baseline in Laboratory Parameters ^[12]

End point description

Number of participants with at least 2-Grade shift from baseline in laboratory parameters are reported. Laboratory parameters included anaemia (AA), white blood cell decreased (WBCD), lymphocyte count decreased (LCD), lymphocyte count increased (LCI), neutrophil count decreased (NCD), platelet count decreased (PCD), hypoalbuminemia (HA),creatinine increased (CI), gamma glutamyl transferase increased (GGTI), hyponatremia (HN), hyperglycemia (HG), serum amylase increased (SAI), aspartate aminotransferase (AST) increased, blood bilirubin increased (BBI), lipase increased (LI), and hypertriglyceridemia (HTG). As-treated population included participants who received any study drugs and were analyzed according to the treatment they actually received. Here, number analyzed (n) denotes, number of participants analyzed for the specified laboratory parameter.

End point type

Primary

End point timeframe

Day 1 (baseline) through 246.9 weeks (maximum observed duration)

Notes
[12] - 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: Statistical analysis was not applicable since there were no inferential statistics, only descriptive statistics were performed for this end point.

End point values	Dose-escalation Cohort 1: Mona 22.5 mg Q2W + Durva	Dose-escalation Cohort 2: Mona 75 mg Q2W + Durva	Dose-escalation Cohort 3: Mona 225 mg Q2W + Durva	Dose-escalation Cohort 4: Mona 750 mg Q2W + Durva	Dose-escalation Cohort 5: Mona 750 mg Q4W + Durva	Dose-expansion Cohort: Mona 750 mg Q2W + Durva (MSS-CRC)	Dose-expansion Cohort: Mona 750 mg Q2W + Durva (ovarian)	Dose-expansion Cohort: Mona 750 mg Q2W+Durva (Endometrial MSS)	Dose-expansion Cohort: Mona 750 mg Q2W + Durva (NSCLC)	Exploration Cohort A1: Mona 750 mg Q2W+Durva + mFOLFOX6 + Beva	Exploration CohortA2: Mona 750 mg Q2W+Durva+mFOLFOX6+Cetu	Exploration Cohort C1A: Mona 750 mg Q2W + Durva + Cetu	Exploration Cohort C1B: Mona 750 mg Q2W + Cetu	Exploration Cohort C2A: Mona 750 mg Q2W + Durva + Cetu	Exploration Cohort C2B: Mona 750 mg Q2W + Cetu
Number of subjects analysed	3	3	3	18	18	40	40	40	20	18	18	39	41	44	37
Units: Participants
AA (n=3,3,3,17,18,40,38,38,20,17,18,39,41,44,37)	0	0	1	2	1	2	1	2	0	1	2	2	2	0	2
WBCD (n=3,3,3,17,18,40,38,38,20,17,18,39,41,44,37)	0	0	0	0	0	1	1	2	0	7	6	0	2	4	1
LCD (n=3,3,3,17,18,40,38,38,20,17,18,39,41,44,37)	0	1	1	4	4	5	7	8	5	5	4	6	3	7	8
LCI (n=0,0,0,0,0,0,0,0,0,17,18,39,41,44,37)	0	0	0	0	0	0	0	0	0	1	0	0	0	0	2
NCD (n=3,3,3,17,18,40,38,38,20,17,18,37,37,36,31)	0	0	0	0	0	1	2	1	0	9	11	0	1	1	1
PCD (n=3,3,3,17,18,40,38,38,20,17,18,39,41,43,37)	0	0	0	0	1	0	1	0	0	2	2	1	0	0	3
HA (n=3,3,3,18,18,40,40,40,20,18,18,39,41,44,36)	1	0	0	6	3	6	6	6	2	2	2	9	2	6	5
CI (n=3,3,3,18,18,40,40,40,20,18,18,0,0,0,0)	1	1	1	1	4	4	4	8	2	4	2	0	0	0	0
GGTI (n=3,3,3,18,18,0,0,0,0,0,0,0,0,0,0)	0	0	0	1	4	0	0	0	0	0	0	0	0	0	0
HN (n=3,3,3,18,18,40,40,40,20,18,18,0,0,0,0)	1	0	1	2	3	3	5	5	1	4	2	0	0	0	0
HG (n=0,0,0,0,0,40,40,40,20,18,18,0,0,0,0)	0	0	0	0	0	3	4	3	5	1	5	0	0	0	0
SAI (n=0,0,0,0,0,0,0,0,0,18,18,0,0,0,0)	0	0	0	0	0	0	0	0	0	4	6	0	0	0	0
ASTI (n=0,0,0,0,0,0,0,0,0,18,18,0,0,0,0)	0	0	0	0	0	0	0	0	0	2	2	0	0	0	0
BBI (n=0,0,0,0,0,0,0,0,0,18,18,39,40,43,37)	0	0	0	0	0	0	0	0	0	3	2	7	7	3	6
LI (n=0,0,0,0,0,0,0,0,0,18,18,39,40,44,36)	0	0	0	0	0	0	0	0	0	5	10	5	6	7	5
HTG (n=0,0,0,0,0,0,0,0,0,18,18,0,0,0,0)	0	0	0	0	0	0	0	0	0	3	3	0	0	0	0

No statistical analyses for this end point

Primary: Number of Participants With Dose Limiting Toxicities (DLTs)

Top of page

End point title

Number of Participants With Dose Limiting Toxicities (DLTs) ^[13] ^[14]

End point description

DLT:Any study drug related Grade (G) 3 or higher toxicity that occurred during DLT evaluation period including: any G>=3 noninfectious colitis/pneumonitis, liver transaminase elevation (TE) >=5 but =<8 upper limit of normal (ULN), any G4 immune-mediated AE (imAE)/immune-related AE (irAE), any G>=3 clinically significant non-hematologic toxicity, TE >8 ULN or total bilirubin (TBL) >5 ULN, increase in AST or ALT >=3 ULN along with TBL >=2 ULN, thrombocytopenia (G3/4 associated with G3/higher hemorrhage, G3 that did not improve by at least 1 grade within 7 days, and G4), G4 febrile neutropenia (FN), G3 FN of >=5 days and G3 FN regardless of duration, G4 neutropenia of >7 days, G3/4 neutropenia not associated with fever/systemic infection, and anemia (G3 and G4). DLT-Evaluable (DLTE) population included all participants enrolled in dose-escalation part who received at least 1 dose of study drugs and completed safety follow-up through DLTE period or experienced any DLT during DLTE period.

End point type

Primary

End point timeframe

From Day 1 to 28 days after the first dose of study drugs

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: Statistical analysis was not applicable since there were no inferential statistics, only descriptive statistics were performed for this end point.
[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: Only those baseline period arms for which analysis was planned were reported in the end point.

End point values	Dose-escalation Cohort 1: Mona 22.5 mg Q2W + Durva	Dose-escalation Cohort 2: Mona 75 mg Q2W + Durva	Dose-escalation Cohort 3: Mona 225 mg Q2W + Durva	Dose-escalation Cohort 4: Mona 750 mg Q2W + Durva	Dose-escalation Cohort 5: Mona 750 mg Q4W + Durva
Number of subjects analysed	3	3	3	17	18
Units: Participants	0	0	0	0	0

No statistical analyses for this end point

Primary: Percentage of Participants With Objective Response (OR) in Exploration Cohorts C1A and C1B

Top of page

End point title

Percentage of Participants With Objective Response (OR) in Exploration Cohorts C1A and C1B ^[15] ^[16]

End point description

The OR is defined as best overall response of confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumours Version 1.1 (RECIST V 1.1) guidelines. The CR is defined as disappearance of all target and non-target lesions and normalization of tumor marker level lesions. The PR is defined as at least a 30% decrease in the sum of the diameters of target lesions (compared to baseline) and no new nontarget lesion. A confirmed PR is defined as two PRs or an un-confirmed PR and an unconfirmed CR that were separated by at least 28 days with no evidence of progression in between. Intent-to-treat (ITT) population included participants who were randomized and were analyzed according to the treatment group they were randomized to.

End point type

Primary

End point timeframe

Baseline (Days -28 to -1) through 54.8 months (maximum observed duration)

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: Statistical analysis was not applicable since there were no inferential statistics, only descriptive statistics were performed for this end point.
[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: Only those baseline period arms for which analysis was planned were reported in the end point.

End point values	Exploration Cohort C1A: Mona 750 mg Q2W + Durva + Cetu	Exploration Cohort C1B: Mona 750 mg Q2W + Cetu
Number of subjects analysed	40	41
Units: Percentage of Participants
number (confidence interval 95%)	0 (0.0 to 10.3)	0 (0.0 to 9.0)

No statistical analyses for this end point

Secondary: Percentage of Participants With OR

Top of page

End point title

Percentage of Participants With OR ^[17]

End point description

The OR is defined as best overall response of CR or confirmed PR according to RECIST V 1.1 guidelines. The CR is defined as disappearance of all target and non-target lesions and normalization of tumor marker level lesions. The PR is defined as at least a 30% decrease in the sum of the diameters of target lesions (compared to baseline) and no new nontarget lesion. A confirmed PR is defined as two PRs or an un-confirmed PR and an unconfirmed CR that were separated by at least 28 days with no evidence of progression in between. As-treated population included participants who received any study drugs and were analyzed according to the treatment they actually received.

End point type

Secondary

End point timeframe

Baseline (Days -28 to -1) through 54.8 months (maximum observed duration)

Notes
[17] - 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: Only those baseline period arms for which analysis was planned were reported in the end point.

End point values	Dose-escalation Cohort 1: Mona 22.5 mg Q2W + Durva	Dose-escalation Cohort 2: Mona 75 mg Q2W + Durva	Dose-escalation Cohort 3: Mona 225 mg Q2W + Durva	Dose-escalation Cohort 4: Mona 750 mg Q2W + Durva	Dose-escalation Cohort 5: Mona 750 mg Q4W + Durva	Dose-expansion Cohort: Mona 750 mg Q2W + Durva (MSS-CRC)	Dose-expansion Cohort: Mona 750 mg Q2W + Durva (ovarian)	Dose-expansion Cohort: Mona 750 mg Q2W+Durva (Endometrial MSS)	Dose-expansion Cohort: Mona 750 mg Q2W + Durva (NSCLC)	Exploration Cohort A1: Mona 750 mg Q2W+Durva + mFOLFOX6 + Beva	Exploration CohortA2: Mona 750 mg Q2W+Durva+mFOLFOX6+Cetu
Number of subjects analysed	3	3	3	18	18	40	40	40	20	18	18
Units: Percentage of Participants
number (confidence interval 95%)	0 (0.0 to 70.8)	0 (0.0 to 70.8)	0 (0.0 to 84.2)	0 (0.0 to 19.5)	0 (0.0 to 19.5)	7.5 (1.6 to 20.4)	5.0 (0.7 to 18.2)	0 (0.0 to 9.5)	10.0 (1.2 to 31.7)	44.4 (23.0 to 72.2)	72.2 (46.5 to 90.3)

No statistical analyses for this end point

Secondary: Percentage of Participants With OR in Exploration Cohorts C2A and C2B

Top of page

End point title

Percentage of Participants With OR in Exploration Cohorts C2A and C2B ^[18]

End point description

The OR is defined as best overall response of confirmed CR or confirmed PR according to RECIST V 1.1 guidelines. The CR is defined as disappearance of all target and non-target lesions and normalization of tumor marker level lesions. The PR is defined as at least a 30% decrease in the sum of the diameters of target lesions (compared to baseline) and no new nontarget lesion. A confirmed PR is defined as two PRs or an un-confirmed PR and an unconfirmed CR that were separated by at least 28 days with no evidence of progression in between. The ITT population included participants who were randomized and were analyzed according to the treatment group they were randomized to.

End point type

Secondary

End point timeframe

Baseline (-28 to -1 day) through 54.8 months (maximum observed duration)

Notes
[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: Only those baseline period arms for which analysis was planned were reported in the end point.

End point values	Exploration Cohort C2A: Mona 750 mg Q2W + Durva + Cetu	Exploration Cohort C2B: Mona 750 mg Q2W + Cetu
Number of subjects analysed	44	37
Units: Percentage of Participants
number (confidence interval 95%)	11.4 (4.0 to 25.6)	5.4 (0.7 to 18.7)

No statistical analyses for this end point

Secondary: Percentage of Participants with Disease Control (DC)

Top of page

End point title

Percentage of Participants with Disease Control (DC) ^[19]

End point description

The DC is defined as best overall response of confirmed CR, confirmed PR, or stable disease (SD) based on RECIST v1.1. The CR is defined as disappearance of all target, non-target lesions and normalization of tumor marker level lesions. The PR is defined as at least a 30% decrease in the sum of the diameters of target lesions (compared to baseline) and no new nontarget lesion. A confirmed PR is defined as two PRs or an un-confirmed PR and an unconfirmed CR that were separated by at least 28 days with no evidence of progression in between. The SD is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. Participants with SD were included in the DC if they maintained SD for >= 8 weeks from start of treatment. The DCR16 and DCR24 are reported (participants with SD >= 16 weeks and >=24 weeks). As-treated population included participants who received any study drugs and were analyzed according to the treatment they actually received.

End point type

Secondary

End point timeframe

Baseline (-28 to -1 day) through 54.8 months (maximum observed duration)

Notes
[19] - 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: Only those baseline period arms for which analysis was planned were reported in the end point.

End point values	Dose-escalation Cohort 1: Mona 22.5 mg Q2W + Durva	Dose-escalation Cohort 2: Mona 75 mg Q2W + Durva	Dose-escalation Cohort 3: Mona 225 mg Q2W + Durva	Dose-escalation Cohort 4: Mona 750 mg Q2W + Durva	Dose-escalation Cohort 5: Mona 750 mg Q4W + Durva	Dose-expansion Cohort: Mona 750 mg Q2W + Durva (MSS-CRC)	Dose-expansion Cohort: Mona 750 mg Q2W + Durva (ovarian)	Dose-expansion Cohort: Mona 750 mg Q2W+Durva (Endometrial MSS)	Dose-expansion Cohort: Mona 750 mg Q2W + Durva (NSCLC)	Exploration Cohort A1: Mona 750 mg Q2W+Durva + mFOLFOX6 + Beva	Exploration CohortA2: Mona 750 mg Q2W+Durva+mFOLFOX6+Cetu
Number of subjects analysed	3	3	3	18	18	40	40	40	20	18	18
Units: Percentage of Participants
number (confidence interval 95%)
DCR16	0 (0.0 to 70.8)	33.3 (0.8 to 90.6)	0 (0.0 to 70.8)	22.2 (6.4 to 47.6)	27.8 (9.7 to 53.5)	30 (16.6 to 46.5)	30 (16.6 to 46.5)	25 (12.7 to 41.2)	40 (19.1 to 63.9)	77.8 (52.4 to 93.6)	88.9 (65.3 to 98.6)
DCR24	0 (0.0 to 70.8)	0 (0.0 to 70.8)	0 (0.0 to 70.8)	0 (0.0 to 18.5)	11.1 (1.4 to 34.7)	17.5 (7.3 to 32.8)	15 (5.7 to 29.8)	12.5 (4.2 to 26.8)	25 (8.7 to 49.1)	66.7 (41.0 to 86.7)	77.8 (52.4 to 93.6)

No statistical analyses for this end point

Secondary: Percentage of Participants with DC in Exploration Cohorts (C1A, C1B, C2A, and C2B)

Top of page

End point title

Percentage of Participants with DC in Exploration Cohorts (C1A, C1B, C2A, and C2B) ^[20]

End point description

The DC is defined as best overall response of confirmed CR, confirmed PR, or SD based on RECIST v1.1. The CR is defined as disappearance of all target and non-target lesions and normalization of tumor marker level lesions. The PR is defined as at least a 30% decrease in the sum of the diameters of target lesions (compared to baseline) and no new nontarget lesion. A confirmed PR is defined as two PRs or an un-confirmed PR and an unconfirmed CR that were separated by at least 28 days with no evidence of progression in between. The SD is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for disease progression. Participants with SD were included in the DC if they maintained SD for >= 8 weeks from start of treatment. The DCR16 and DCR24 are reported (participants with SD >= 16 weeks and >=24 weeks). The ITT population included participants who were randomized and were analyzed according to the treatment group they were randomized to.

End point type

Secondary

End point timeframe

Baseline (-28 to -1 day) through 54.8 months (maximum observed duration)

Notes
[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: Only those baseline period arms for which analysis was planned were reported in the end point.

End point values	Exploration Cohort C1A: Mona 750 mg Q2W + Durva + Cetu	Exploration Cohort C1B: Mona 750 mg Q2W + Cetu	Exploration Cohort C2A: Mona 750 mg Q2W + Durva + Cetu	Exploration Cohort C2B: Mona 750 mg Q2W + Cetu
Number of subjects analysed	40	41	44	37
Units: Percentage of Participants
number (confidence interval 95%)
DCR16	17.5 (7.3 to 32.8)	34.1 (20.1 to 50.6)	59.1 (43.2 to 73.7)	56.8 (39.5 to 72.9)
DCR24	10.0 (2.8 to 23.7)	7.3 (1.5 to 19.9)	52.3 (36.7 to 67.5)	45.9 (29.5 to 63.1)

No statistical analyses for this end point

Secondary: Duration of Response (DoR)

Top of page

End point title

Duration of Response (DoR) ^[21]

End point description

The DoR is defined as the duration from the first documentation of OR (confirmed 2 CRs [disappearance of all target, non-target lesions and normalization of tumor marker level lesions] or confirmed 2 PRs [>= 30% decrease in the sum of diameters of target lesions compared to baseline and no new non-target lesion]) to the first documented PD based on RECIST v1.1 or death due to any cause, whichever occurred first. The 2 CRs and/or 2 PRs should be separated by at least 28 days with no evidence of progression in-between. The DoR was evaluated using Kaplan-Meier method. The arbitrary number 99999 signified upper limit confidence interval (CI) could not be derived due to insufficient events being observed. As-treated population included participants who received any study drugs and were analyzed according to the treatment they actually received. Participants who had achieved OR were evaluated for this end point.

End point type

Secondary

End point timeframe

Baseline (-28 to -1 day) through 54.8 months (maximum observed duration)

Notes
[21] - 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: Only those baseline period arms for which analysis was planned were reported in the end point.

End point values	Dose-escalation Cohort 1: Mona 22.5 mg Q2W + Durva	Dose-escalation Cohort 2: Mona 75 mg Q2W + Durva	Dose-escalation Cohort 3: Mona 225 mg Q2W + Durva	Dose-escalation Cohort 4: Mona 750 mg Q2W + Durva	Dose-escalation Cohort 5: Mona 750 mg Q4W + Durva	Dose-expansion Cohort: Mona 750 mg Q2W + Durva (MSS-CRC)	Dose-expansion Cohort: Mona 750 mg Q2W + Durva (ovarian)	Dose-expansion Cohort: Mona 750 mg Q2W+Durva (Endometrial MSS)	Dose-expansion Cohort: Mona 750 mg Q2W + Durva (NSCLC)	Exploration Cohort A1: Mona 750 mg Q2W+Durva + mFOLFOX6 + Beva	Exploration CohortA2: Mona 750 mg Q2W+Durva+mFOLFOX6+Cetu
Number of subjects analysed	0 ^[22]	0 ^[23]	0 ^[24]	0 ^[25]	0 ^[26]	3	2	0 ^[27]	2	8	13
Units: Weeks
median (confidence interval 95%)	( to )	( to )	( to )	( to )	( to )	16.1 (15.9 to 99999)	68.1 (24.0 to 99999)	( to )	22.9 (10.1 to 99999)	66.1 (16.1 to 85.4)	72.3 (17.4 to 99999)

Notes
[22] - No participant has achieved OR in this treatment arm group.
[23] - No participant has achieved OR in this treatment arm group.
[24] - No participant has achieved OR in this treatment arm group.
[25] - No participant has achieved OR in this treatment arm group.
[26] - No participant has achieved OR in this treatment arm group.
[27] - No participant has achieved OR in this treatment arm group.

No statistical analyses for this end point

Secondary: DoR in Exploration Cohorts (C1A, C1B, C2A, and C2B)

Top of page

End point title

DoR in Exploration Cohorts (C1A, C1B, C2A, and C2B) ^[28]

End point description

The DoR is defined as the duration from the first documentation of OR (confirmed 2 CRs [disappearance of all target, non-target lesions and normalization of tumor marker level lesions] or confirmed 2 PRs [(>= 30% decrease in the sum of diameters of target lesions compared to baseline and no new non-target lesion]) to the first documented PD based on RECIST v1.1 or death due to any cause, whichever occurred first. The 2 CRs and/or 2 PRs should be separated by at least 28 days with no evidence of progression in-between. The DoR was evaluated using Kaplan-Meier method. The arbitrary number 99999 signified upper limit CI could not be derived due to insufficient events being observed. The ITT population included participants who were randomized and were analyzed according to the treatment group they were randomized to. Participants who had achieved OR were evaluated for this end point.

End point type

Secondary

End point timeframe

Baseline (-28 to -1 day) through 54.8 months (maximum observed duration)

Notes
[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: Only those baseline period arms for which analysis was planned were reported in the end point.

End point values	Exploration Cohort C1A: Mona 750 mg Q2W + Durva + Cetu	Exploration Cohort C1B: Mona 750 mg Q2W + Cetu	Exploration Cohort C2A: Mona 750 mg Q2W + Durva + Cetu	Exploration Cohort C2B: Mona 750 mg Q2W + Cetu
Number of subjects analysed	0 ^[29]	0 ^[30]	5	2
Units: Weeks
median (confidence interval 95%)	( to )	( to )	32.1 (16.0 to 99999)	24.1 (12.1 to 99999)

Notes
[29] - No participant has achieved OR in this treatment arm group.
[30] - No participant has achieved OR in this treatment arm group.

No statistical analyses for this end point

Secondary: Progression-Free Survival (PFS)

Top of page

End point title

Progression-Free Survival (PFS) ^[31]

End point description

The PFS is defined as the time from the start of study treatment until the first documentation of PD based on RECIST v1.1 or death due to any cause, whichever occurred first. The PD is defined as at least a 20% increase in the sum of diameters of target lesions or unequivocal progression of existing non-target lesions, taking as reference the smallest sum on study and appearance of one or more new lesions. The arbitrary numbers 0.99999 and 99999 signified the data for lower and upper limit of CI could not be derived due to insufficient events being observed. The PFS was estimated using Kaplan-Meier method. As-treated population included participants who received any study drugs and were analyzed according to the treatment they actually received.

End point type

Secondary

End point timeframe

Baseline (-28 to -1 day) through 54.8 months (maximum observed duration)

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: Only those baseline period arms for which analysis was planned were reported in the end point.

End point values	Dose-escalation Cohort 1: Mona 22.5 mg Q2W + Durva	Dose-escalation Cohort 2: Mona 75 mg Q2W + Durva	Dose-escalation Cohort 3: Mona 225 mg Q2W + Durva	Dose-escalation Cohort 4: Mona 750 mg Q2W + Durva	Dose-escalation Cohort 5: Mona 750 mg Q4W + Durva	Dose-expansion Cohort: Mona 750 mg Q2W + Durva (MSS-CRC)	Dose-expansion Cohort: Mona 750 mg Q2W + Durva (ovarian)	Dose-expansion Cohort: Mona 750 mg Q2W+Durva (Endometrial MSS)	Dose-expansion Cohort: Mona 750 mg Q2W + Durva (NSCLC)	Exploration Cohort A1: Mona 750 mg Q2W+Durva + mFOLFOX6 + Beva	Exploration CohortA2: Mona 750 mg Q2W+Durva+mFOLFOX6+Cetu
Number of subjects analysed	3	3	3	18	18	40	40	40	20	18	18
Units: Months
median (confidence interval 95%)	1.8 (1.7 to 99999)	1.9 (1.8 to 99999)	1.9 (0.99999 to 99999)	2.0 (1.7 to 3.4)	1.8 (1.7 to 3.5)	1.9 (1.8 to 3.6)	1.8 (1.7 to 1.9)	1.8 (1.7 to 3.3)	1.9 (1.7 to 3.7)	10.9 (5.7 to 17.7)	14.7 (5.8 to 20.9)

No statistical analyses for this end point

Secondary: Progression-Free Survival (PFS) in Exploration Cohorts (C1A, C1B, C2A, and C2B)

Top of page

End point title

Progression-Free Survival (PFS) in Exploration Cohorts (C1A, C1B, C2A, and C2B) ^[32]

End point description

The PFS is defined as the time from the start of study treatment until the first documentation of PD based on RECIST v1.1 or death due to any cause, whichever occurred first. The PD is defined as at least a 20% increase in the sum of diameters of target lesions or unequivocal progression of existing non-target lesions, taking as reference the smallest sum on study and appearance of one or more new lesions. The PFS was estimated using Kaplan-Meier method. The ITT population included participants who were randomized and were analyzed according to the treatment group they were randomized to.

End point type

Secondary

End point timeframe

Baseline (-28 to -1 day) through 54.8 months (maximum observed duration)

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: Only those baseline period arms for which analysis was planned were reported in the end point.

End point values	Exploration Cohort C1A: Mona 750 mg Q2W + Durva + Cetu	Exploration Cohort C1B: Mona 750 mg Q2W + Cetu	Exploration Cohort C2A: Mona 750 mg Q2W + Durva + Cetu	Exploration Cohort C2B: Mona 750 mg Q2W + Cetu
Number of subjects analysed	40	41	44	37
Units: Months
median (confidence interval 95%)	1.8 (1.7 to 1.9)	2.0 (1.7 to 3.3)	5.3 (3.2 to 5.5)	4.4 (2.1 to 5.5)

No statistical analyses for this end point

Secondary: Overall Survival

Top of page

End point title

Overall Survival ^[33]

End point description

The overall survival is defined as the time from the start of study treatment until death due to any cause. The OS was estimated using Kaplan-Meier method. As-treated population included participants who received any study drugs and were analyzed according to the treatment they actually received. The arbitrary numbers 0.99999, 99999, and 99.999 signified the data for lower limit of CI, upper limit of CI, and median, respectively, could note be derived due to insufficient events being observed.

End point type

Secondary

End point timeframe

Baseline (-28 to -1 day) through 54.8 months (maximum observed duration)

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: Only those baseline period arms for which analysis was planned were reported in the end point.

End point values	Dose-escalation Cohort 1: Mona 22.5 mg Q2W + Durva	Dose-escalation Cohort 2: Mona 75 mg Q2W + Durva	Dose-escalation Cohort 3: Mona 225 mg Q2W + Durva	Dose-escalation Cohort 4: Mona 750 mg Q2W + Durva	Dose-escalation Cohort 5: Mona 750 mg Q4W + Durva	Dose-expansion Cohort: Mona 750 mg Q2W + Durva (MSS-CRC)	Dose-expansion Cohort: Mona 750 mg Q2W + Durva (ovarian)	Dose-expansion Cohort: Mona 750 mg Q2W+Durva (Endometrial MSS)	Dose-expansion Cohort: Mona 750 mg Q2W + Durva (NSCLC)	Exploration Cohort A1: Mona 750 mg Q2W+Durva + mFOLFOX6 + Beva	Exploration CohortA2: Mona 750 mg Q2W+Durva+mFOLFOX6+Cetu
Number of subjects analysed	3	3	3	18	18	40	40	40	20	18	18
Units: Months
median (confidence interval 95%)	15.1 (0.99999 to 99999)	20.1 (18.6 to 99999)	99.999 (0.9999 to 99999)	8.1 (4.0 to 16.7)	13.4 (4.4 to 16.9)	10.6 (6.0 to 20.1)	16.7 (10.7 to 21.4)	11.0 (6.7 to 17.3)	8.8 (5.8 to 15.6)	25.6 (13.8 to 99999)	29.6 (19.8 to 99999)

No statistical analyses for this end point

Secondary: Overall Survival in Exploration Cohorts (C1A, C1B, C2A, and C2B)

Top of page

End point title

Overall Survival in Exploration Cohorts (C1A, C1B, C2A, and C2B) ^[34]

End point description

The overall survival is defined as the time from the start of study treatment until death due to any cause. The overall survival was estimated using Kaplan-Meier method. The ITT population included participants who were randomized and were analyzed according to the treatment group they were randomized to.

End point type

Secondary

End point timeframe

Baseline (-28 to -1 day) through 54.8 weeks (maximum observed duration)

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: Only those baseline period arms for which analysis was planned were reported in the end point.

End point values	Exploration Cohort C1A: Mona 750 mg Q2W + Durva + Cetu	Exploration Cohort C1B: Mona 750 mg Q2W + Cetu	Exploration Cohort C2A: Mona 750 mg Q2W + Durva + Cetu	Exploration Cohort C2B: Mona 750 mg Q2W + Cetu
Number of subjects analysed	40	41	44	37
Units: Months
median (confidence interval 95%)	10.3 (4.3 to 12.7)	8.9 (6.8 to 11.3)	14.6 (10.0 to 19.4)	14.6 (7.2 to 18.7)

No statistical analyses for this end point

Secondary: Maximum Observed Serum Concentration (Cmax) of Monalizumab

Top of page

End point title

Maximum Observed Serum Concentration (Cmax) of Monalizumab ^[35]

End point description

Serum Cmax of monalizumab at pre-dose and end of infusion are reported. The arbitrary number 99999 signified standard deviation was not reported as only one participant was evaluable for the specified arm. Pharmacokinetic evaluable population included participants who received at least 1 dose of durvalumab and/or monalizumab and had at least 1 post-treatment sample available. Number of subjects analyzed denotes those subjects who had adequate PK sample available for analysis. Data for dose-escalation Cohort 4 and dose-expansion Cohorts (MSS-CRC, Ovarian, Endometrial MSS and NSCLC) were combined in a single arm/group to avoid increased variability due to smaller cohort sizes.

End point type

Secondary

End point timeframe

Day 85: Pre-dose and end of infusion (within 10 minutes) after cohort specific infusions

Notes
[35] - 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: Only those baseline period arms for which analysis was planned were reported in the end point.

End point values	Dose-escalation Cohort 1: Mona 22.5 mg Q2W + Durva	Dose-escalation Cohort 2: Mona 75 mg Q2W + Durva	Dose-escalation Cohort 3: Mona 225 mg Q2W + Durva	Dose-escalation Cohort 5: Mona 750 mg Q4W + Durva	Exploration Cohort A1: Mona 750 mg Q2W+Durva + mFOLFOX6 + Beva	Exploration CohortA2: Mona 750 mg Q2W+Durva+mFOLFOX6+Cetu	Exploration Cohort C1A: Mona 750 mg Q2W + Durva + Cetu	Exploration Cohort C1B: Mona 750 mg Q2W + Cetu	Exploration Cohort C2A: Mona 750 mg Q2W + Durva + Cetu	Exploration Cohort C2B: Mona 750 mg Q2W + Cetu	Dose-escalation Cohort4+Dose-expansion: Mona 750mg Q2W + Durva
Number of subjects analysed	1	2	1	6	7	9	10	11	19	19	60
Units: µg/mL
arithmetic mean (standard deviation)	7.85 ± 99999	43.62 ± 12.54	144.88 ± 99999	245.18 ± 142.35	304.48 ± 66.75	281.53 ± 155.57	346.85 ± 91.06	388.60 ± 194.64	289.25 ± 194.59	409.93 ± 175.43	315.74 ± 129.08

No statistical analyses for this end point

Secondary: Minimum Observed Serum Concentration (Cmin) of Monalizumab

Top of page

End point title

Minimum Observed Serum Concentration (Cmin) of Monalizumab ^[36]

End point description

Serum Cmin of monalizumab at pre-dose and end of infusion are reported. The arbitrary number 99999 signified standard deviation was not reported as only one participant was evaluable for the specified arm. Pharmacokinetic evaluable population included participants who received at least 1 dose of durvalumab and/or monalizumab and had at least 1 post-treatment sample available. Number of subjects analyzed denotes those subjects who had adequate PK sample available for analysis. Data for dose-escalation Cohort 4 and dose-expansion Cohorts (MSS-CRC, Ovarian, Endometrial MSS and NSCLC) were combined in a single arm/group to avoid increased variability due to smaller cohort sizes.

End point type

Secondary

End point timeframe

Day 85: Pre-dose and end of infusion (within 10 minutes) after cohort specific infusions

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: Only those baseline period arms for which analysis was planned were reported in the end point.

End point values	Dose-escalation Cohort 1: Mona 22.5 mg Q2W + Durva	Dose-escalation Cohort 2: Mona 75 mg Q2W + Durva	Dose-escalation Cohort 3: Mona 225 mg Q2W + Durva	Dose-escalation Cohort 5: Mona 750 mg Q4W + Durva	Exploration Cohort A1: Mona 750 mg Q2W+Durva + mFOLFOX6 + Beva	Exploration CohortA2: Mona 750 mg Q2W+Durva+mFOLFOX6+Cetu	Exploration Cohort C1A: Mona 750 mg Q2W + Durva + Cetu	Exploration Cohort C1B: Mona 750 mg Q2W + Cetu	Exploration Cohort C2A: Mona 750 mg Q2W + Durva + Cetu	Exploration Cohort C2B: Mona 750 mg Q2W + Cetu	Dose-escalation Cohort4+Dose-expansion: Mona 750mg Q2W + Durva
Number of subjects analysed	1	2	1	6	10	11	11	11	22	22	61
Units: µg/mL
arithmetic mean (standard deviation)	7.45 ± 99999	18.16 ± 6.70	92.55 ± 99999	67.75 ± 57.82	141.39 ± 57.01	109.18 ± 45.54	129.59 ± 45.72	172.90 ± 84.55	148.05 ± 70.23	185.60 ± 105.68	145.04 ± 76.34

No statistical analyses for this end point

Secondary: Serum Concentration of Durvalumab

Top of page

End point title

Serum Concentration of Durvalumab

End point description

Serum concentration of durvalumab is reported. Pharmacokinetic evaluable population included participants who received at least 1 dose of durvalumab and/or monalizumab and had at least 1 post-treatment sample available. Number analyzed (n) denotes those participants who had adequate PK sample available for analysis for specified time point. The data is combined in a single arm with a respectable sample size as values from different cohorts with small cohort size will increase variability.

End point type

Secondary

End point timeframe

Pre-dose (PRE) on Day 1 of Weeks 1, 5, 9, 13, and 25 and post-dose (POST) on Day 1 of Weeks 1 and 13

End point values	Dose-escalation (1-5) + dose-expansion + dose-exploration
Number of subjects analysed	287
Units: µg/mL
arithmetic mean (standard deviation)
Week 1 Day 1 (PRE) (n=287)	0.100 ± 0.63
Week 1 Day 1 (POST) (n=285)	399 ± 157
Week 5 Day 1 (PRE) (n=248)	90.8 ± 95.0
Week 9 Day 1 (PRE) (n=193)	127 ± 148
Week 13 Day 1 (PRE) (n=140)	142 ± 123
Week 13 Day 1 (POST) (n=126)	497 ± 277
Week 25 Day 1 (PRE) (n=79)	149 ± 109

No statistical analyses for this end point

Secondary: Serum Concentration of Cetuximab

Top of page

End point title

Serum Concentration of Cetuximab

End point description

Serum concentration of cetuximab is reported. Pharmacokinetic evaluable population included participants who received at least 1 dose of durvalumab and/or monalizumab and had at least 1 post-treatment sample available. Number analyzed (n) denotes those participants who had adequate PK sample available for analysis for specified time point. The data is combined in a single arm with a respectable sample size as values from different cohorts with small cohort size will increase variability.

End point type

Secondary

End point timeframe

Pre-dose (PRE) on Day 1 of Week 1, 5, 9, 13, and post-dose (POST) on Day 1 of Week 1, 5, and 13 at the end of infusion

End point values	Exploration Cohorts A2, C1A, C2A, C1B, and C2B
Number of subjects analysed	70
Units: µg/mL
arithmetic mean (standard deviation)
Week 1 Day 1 (PRE) (n=54)	0.025 ± 0.00
Week 1 Day 1 (POST) (n=70)	400 ± 138
Week 5 Day 1 (PRE) (n=48)	73.6 ± 108.0
Week 5 Day 1 (POST) (n=6)	344 ± 161
Week 9 Day 1 (PRE) (n=18)	97.7 ± 137
Week 13 Day 1 (PRE) (n=19)	61.7 ± 113
Week 13 Day 1 (POST) (n=20)	387 ± 101

No statistical analyses for this end point

Secondary: Number of Participants With Positive Anti-Drug Antibodies (ADA) to Monalizumab

Top of page

End point title

Number of Participants With Positive Anti-Drug Antibodies (ADA) to Monalizumab

End point description

Number of participants with positive ADA to monalizumab are reported. Persistent positive is defined as positive at >=2 post-baseline assessments (with >=16 weeks between first and last positive) or positive at last post-baseline assessment. Transient positive is defined as negative at last post-baseline assessment and positive at only one post-baseline assessment or at >=2 post-baseline assessments (with <16 weeks between first and last positive). Treatment-boosted ADA is defined as baseline ADA titer that was boosted to a 4-fold or higher-level following drug administration. Treatment-emergent ADA is defined as the sum of treatment-induced ADA (post-baseline positive only) and treatment-boosted ADA. As-treated population included participants who received any study drugs and were analyzed according to the treatment they actually received. Here, number of subjects analyzed denotes those participants who had post-baseline ADA results.

End point type

Secondary

End point timeframe

Day 1 through 54.8 months (Day 1 of Weeks 1, 5, 13, and 25, and 90 days after the last dose of monalizumab)

End point values	Dose-escalation Cohort 1: Mona 22.5 mg Q2W + Durva	Dose-escalation Cohort 2: Mona 75 mg Q2W + Durva	Dose-escalation Cohort 3: Mona 225 mg Q2W + Durva	Dose-escalation Cohort 4: Mona 750 mg Q2W + Durva	Dose-escalation Cohort 5: Mona 750 mg Q4W + Durva	Dose-expansion Cohort: Mona 750 mg Q2W + Durva (MSS-CRC)	Dose-expansion Cohort: Mona 750 mg Q2W + Durva (ovarian)	Dose-expansion Cohort: Mona 750 mg Q2W+Durva (Endometrial MSS)	Dose-expansion Cohort: Mona 750 mg Q2W + Durva (NSCLC)	Exploration Cohort A1: Mona 750 mg Q2W+Durva + mFOLFOX6 + Beva	Exploration CohortA2: Mona 750 mg Q2W+Durva+mFOLFOX6+Cetu	Exploration Cohort C1A: Mona 750 mg Q2W + Durva + Cetu	Exploration Cohort C1B: Mona 750 mg Q2W + Cetu	Exploration Cohort C2A: Mona 750 mg Q2W + Durva + Cetu	Exploration Cohort C2B: Mona 750 mg Q2W + Cetu
Number of subjects analysed	3	3	3	15	16	36	35	32	18	16	18	30	38	37	34
Units: Participants
Persistent Positive	0	0	0	2	0	10	5	4	2	0	1	5	5	3	5
Transient Positive	0	0	0	1	0	1	2	1	2	0	0	1	1	2	0
Treatment-boosted ADA	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Treatment-emergent ADA	0	0	0	3	0	11	7	5	4	0	1	6	6	5	5

No statistical analyses for this end point

Secondary: Number of Participants With Positive ADA to Durvalumab

Top of page

End point title

Number of Participants With Positive ADA to Durvalumab

End point description

Number of participants with positive ADA to monalizumab are reported. The persistent positive is defined as positive at >=2 post-baseline assessments (with >=16 weeks between first and last positive) or positive at last post-baseline assessment. The transient positive is defined as negative at last post-baseline assessment and positive at only one post-baseline assessment or at >= 2 post-baseline assessments (with <16 weeks between first and last positive). The treatment-boosted ADA is defined as baseline ADA titer that was boosted to a 4-fold or higher-level following drug administration. The treatment-emergent ADA is defined as the sum of treatment-induced ADA (post-baseline positive only) and treatment-boosted ADA. As-treated population included participants who received any study drugs and were analyzed according to the treatment they actually received. Here, number of subjects analyzed denotes those participants who had post-baseline ADA results.

End point type

Secondary

End point timeframe

Day 1 through 54.8 months (Day 1 of Weeks 1, 5, 13, and 25, and 90 days after the last dose of monalizumab)

End point values	Dose-escalation Cohort 1: Mona 22.5 mg Q2W + Durva	Dose-escalation Cohort 2: Mona 75 mg Q2W + Durva	Dose-escalation Cohort 3: Mona 225 mg Q2W + Durva	Dose-escalation Cohort 4: Mona 750 mg Q2W + Durva	Dose-escalation Cohort 5: Mona 750 mg Q4W + Durva	Dose-expansion Cohort: Mona 750 mg Q2W + Durva (MSS-CRC)	Dose-expansion Cohort: Mona 750 mg Q2W + Durva (ovarian)	Dose-expansion Cohort: Mona 750 mg Q2W+Durva (Endometrial MSS)	Dose-expansion Cohort: Mona 750 mg Q2W + Durva (NSCLC)	Exploration Cohort A1: Mona 750 mg Q2W+Durva + mFOLFOX6 + Beva	Exploration CohortA2: Mona 750 mg Q2W+Durva+mFOLFOX6+Cetu	Exploration Cohort C1A: Mona 750 mg Q2W + Durva + Cetu	Exploration Cohort C1B: Mona 750 mg Q2W + Cetu	Exploration Cohort C2A: Mona 750 mg Q2W + Durva + Cetu	Exploration Cohort C2B: Mona 750 mg Q2W + Cetu
Number of subjects analysed	3	3	3	15	9	36	33	31	18	17	18	30	2	39	1
Units: Participants
Persistent Positive	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0
Transient Positive	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Treatment-boosted ADA	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Treatment-emergent ADA	0	0	0	0	1	1	0	0	0	0	0	0	0	0	0

No statistical analyses for this end point

Secondary: Number of Participants With Positive ADA to Cetuximab

Top of page

End point title

Number of Participants With Positive ADA to Cetuximab ^[37]

End point description

Number of participants with positive ADA to cetuximab are reported. The persistent positive is defined as positive at >=2 post-baseline assessments (with >=16 weeks between first and last positive) or positive at last post-baseline assessment. The transient positive is defined as negative at last post-baseline assessment and positive at only one post-baseline assessment or at >= 2 post-baseline assessments (with <16 weeks between first and last positive). The treatment-boosted ADA is defined as baseline ADA titer that was boosted to a 4-fold or higher-level following drug administration. The treatment-emergent ADA is defined as the sum of treatment-induced ADA (post-baseline positive only) and treatment-boosted ADA. As-treated population included participants who received any study drugs and were analyzed according to the treatment they actually received. Here, number of subjects analyzed denotes those participants who had post-baseline ADA results.

End point type

Secondary

End point timeframe

Day 1 through 54.8 months (Day 1 of Weeks 1, 5, 9 [if EOT occurred], and 13, and 30 days after the last dose of monalizumab)

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: Only those baseline period arms for which analysis was planned were reported in the end point.

End point values	Exploration CohortA2: Mona 750 mg Q2W+Durva+mFOLFOX6+Cetu	Exploration Cohort C1A: Mona 750 mg Q2W + Durva + Cetu	Exploration Cohort C1B: Mona 750 mg Q2W + Cetu	Exploration Cohort C2A: Mona 750 mg Q2W + Durva + Cetu	Exploration Cohort C2B: Mona 750 mg Q2W + Cetu
Number of subjects analysed	18	28	35	1	0 ^[38]
Units: Participants
Persistent Positive	0	1	0	0
Transient Positive	0	0	0	0
Treatment-boosted ADA	0	0	0	0
Treatment-emergent ADA	0	1	0	0

Notes
[38] - No participant had adequate ADA sample.

No statistical analyses for this end point

Secondary: Number of Participants With Programmed Death Ligand 1 (PD-L1) Expression in Pretreatment Tumor Biopsies

Top of page

End point title

Number of Participants With Programmed Death Ligand 1 (PD-L1) Expression in Pretreatment Tumor Biopsies

End point description

Number of participants with PD-L1 expression in pre-treatment tumor biopsies is reported. The participants were stratified into four categories: tumor cells (TC) >= 25%, TC<25%, TC>=1%, and TC<1%, based on the historical use of PD-L1 cutoffs. As-treated population included participants who received any study drugs and were analyzed according to the treatment they actually received. Here, number of subjects analyzed denotes those participants for whom PD-L1 testing was performed, and for whom PD-L1 status was obtained.

End point type

Secondary

End point timeframe

Screening (Days -28 to -1)

End point values	Dose-escalation Cohort 1: Mona 22.5 mg Q2W + Durva	Dose-escalation Cohort 2: Mona 75 mg Q2W + Durva	Dose-escalation Cohort 3: Mona 225 mg Q2W + Durva	Dose-escalation Cohort 4: Mona 750 mg Q2W + Durva	Dose-escalation Cohort 5: Mona 750 mg Q4W + Durva	Dose-expansion Cohort: Mona 750 mg Q2W + Durva (MSS-CRC)	Dose-expansion Cohort: Mona 750 mg Q2W + Durva (ovarian)	Dose-expansion Cohort: Mona 750 mg Q2W+Durva (Endometrial MSS)	Dose-expansion Cohort: Mona 750 mg Q2W + Durva (NSCLC)	Exploration Cohort A1: Mona 750 mg Q2W+Durva + mFOLFOX6 + Beva	Exploration CohortA2: Mona 750 mg Q2W+Durva+mFOLFOX6+Cetu	Exploration Cohort C1A: Mona 750 mg Q2W + Durva + Cetu	Exploration Cohort C1B: Mona 750 mg Q2W + Cetu	Exploration Cohort C2A: Mona 750 mg Q2W + Durva + Cetu	Exploration Cohort C2B: Mona 750 mg Q2W + Cetu
Number of subjects analysed	3	3	3	13	14	29	37	32	16	16	18	31	33	36	32
Units: Participants
TC>=25%	0	0	0	2	1	0	5	1	6	0	0	0	1	1	0
TC<25%	3	3	3	11	13	29	32	31	10	16	18	31	32	35	32
TC>=1%	1	1	1	6	2	5	22	16	8	3	0	5	7	7	5
TC<1%	2	2	2	7	12	24	15	16	8	13	18	26	26	29	27

No statistical analyses for this end point

Secondary: Number of Participants With Human Leukocyte Antigen (HLA)-E Expression in Pretreatment Tumor Biopsies

Top of page

End point title

Number of Participants With Human Leukocyte Antigen (HLA)-E Expression in Pretreatment Tumor Biopsies

End point description

The HLA-E expression in pre-treatment tumor biopsies is reported. As-treated population included participants who received any study drugs and were analyzed according to the treatment they actually received.

End point type

Secondary

End point timeframe

Screening (Days -28 to -1)

End point values	Dose-escalation Cohort 1: Mona 22.5 mg Q2W + Durva	Dose-escalation Cohort 2: Mona 75 mg Q2W + Durva	Dose-escalation Cohort 3: Mona 225 mg Q2W + Durva	Dose-escalation Cohort 4: Mona 750 mg Q2W + Durva	Dose-escalation Cohort 5: Mona 750 mg Q4W + Durva	Dose-expansion Cohort: Mona 750 mg Q2W + Durva (MSS-CRC)	Dose-expansion Cohort: Mona 750 mg Q2W + Durva (ovarian)	Dose-expansion Cohort: Mona 750 mg Q2W+Durva (Endometrial MSS)	Dose-expansion Cohort: Mona 750 mg Q2W + Durva (NSCLC)	Exploration Cohort A1: Mona 750 mg Q2W+Durva + mFOLFOX6 + Beva	Exploration CohortA2: Mona 750 mg Q2W+Durva+mFOLFOX6+Cetu	Exploration Cohort C1A: Mona 750 mg Q2W + Durva + Cetu	Exploration Cohort C1B: Mona 750 mg Q2W + Cetu	Exploration Cohort C2A: Mona 750 mg Q2W + Durva + Cetu	Exploration Cohort C2B: Mona 750 mg Q2W + Cetu
Number of subjects analysed	3	3	3	18	18	40	40	40	20	18	18	39	41	44	37
Units: Participants
HLA-E Carcinoma	3	3	3	12	13	28	36	32	16	16	17	30	33	34	32
HLA-E Lymphocyte	3	3	3	12	13	30	37	32	17	16	17	29	32	34	32
HLA-E Endothelium	3	3	3	13	13	30	37	33	17	16	17	30	31	34	32

No statistical analyses for this end point

Adverse events

Top of page

Timeframe for reporting adverse events

Day 1 through 246.9 weeks (maximum observed duration)

Adverse event reporting additional description

Total number of death data was analysed as per ITT population, and AE/SAE data was analysed as per As-treated population.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

24.1

Reporting group title

Dose-escalation Cohort 1: Mona 22.5 mg Q2W + Durva

Reporting group description

Participants received intravenous (IV) infusions of durvalumab 1500 mg every 4 weeks (Q4W) in combination with monalizumab 22.5 mg every 2 weeks (Q2W) up to 3 years until unacceptable toxicity, documentation of confirmed disease progression (PD), or documentation of subject withdrawal for another reason.

Reporting group title

Dose-escalation Cohort 2: Mona 75 mg Q2W + Durva

Reporting group description

Reporting group title

Exploration CohortA2: Mona 750 mg Q2W+Durva+mFOLFOX6+Cetu

Reporting group description

Participants with 1L MSS-CRC received IV infusions of durvalumab 1500 mg Q4W in combination with monalizumab 750 mg Q2W, plus mFOLFOX6 (oxaliplatin 85 mg/m^2, folinic acid 400 mg/m^2, fluorouracil 400 mg/m^2 IV bolus, followed by 2400 mg/m^2 continuous IV infusion over 46 to 48 hours on Day 1) Q2W plus IV infusion of cetuximab (loading dose of 400 mg/m^2 on Day 1, followed by maintenance dose of 250 mg/m^2 IV infusion every week starting on Day 8, then changed to 500 mg/m^2 IV infusion Q2W) up to 3 years until unacceptable toxicity, documentation of confirmed PD, or documentation of subject withdrawal for another reason.

Reporting group title

Exploration CohortA1: Mona 750 mg Q2W+Durva + mFOLFOX6 + Beva

Reporting group description

Participants with first-line (1L) MSS-CRC received IV infusions of durvalumab 1500 mg Q4W in combination with monalizumab 750 mg Q2W plus mFOLFOX (oxaliplatin 85 mg/m^2 IV infusion, folinic acid 400 mg/m^2 infusion, fluorouracil 400 mg/m^2 IV bolus, followed by 2400 mg/m^2 continuous IV infusion over 46 to 48 hours on Day 1) Q2W plus IV infusion of bevacizumab 5 mg/kg Q2W up to 3 years until unacceptable toxicity, documentation of confirmed PD, or documentation of subject withdrawal for another reason.

Reporting group title

Dose-expansion Cohort: Mona 750 mg Q2W + Durva (NSCLC)

Reporting group description

Reporting group title

Dose-escalation Cohort 3: Mona 225 mg Q2W + Durva

Reporting group description

Reporting group title

Dose-escalation Cohort 4: Mona 750 mg Q2W + Durva

Reporting group description

Reporting group title

Dose-escalation Cohort 5: Mona 750 mg Q4W + Durva

Reporting group description

Reporting group title

Dose-expansion Cohort: Mona 750 mg Q2W + Durva (MSS-CRC)

Reporting group description

Reporting group title

Dose-expansion Cohort: Mona 750 mg Q2W + Durva (ovarian)

Reporting group description

Reporting group title

Dose-expansion Cohort: Mona 750 mg Q2W+Durva (Endometrial MSS)

Reporting group description

Reporting group title

Exploration Cohort C2A: Mona 750 mg Q2W + Durva + Cetu

Reporting group description

Reporting group title

Exploration Cohort C1B: Mona 750 mg Q2W + Cetu

Reporting group description

Reporting group title

Exploration Cohort C1A: Mona 750 mg Q2W + Durva + Cetu

Reporting group description

Reporting group title

Exploration Cohort C2B: Mona 750 mg Q2W + Cetu

Reporting group description

Dose-escalation Cohort 1: Mona 22.5 mg Q2W + Durva

Dose-escalation Cohort 2: Mona 75 mg Q2W + Durva

Exploration CohortA2: Mona 750 mg Q2W+Durva+mFOLFOX6+Cetu

Exploration CohortA1: Mona 750 mg Q2W+Durva + mFOLFOX6 + Beva

Dose-expansion Cohort: Mona 750 mg Q2W + Durva (NSCLC)

Dose-escalation Cohort 3: Mona 225 mg Q2W + Durva

Dose-escalation Cohort 4: Mona 750 mg Q2W + Durva

Dose-escalation Cohort 5: Mona 750 mg Q4W + Durva

Dose-expansion Cohort: Mona 750 mg Q2W + Durva (MSS-CRC)

Dose-expansion Cohort: Mona 750 mg Q2W + Durva (ovarian)

Dose-expansion Cohort: Mona 750 mg Q2W+Durva (Endometrial MSS)

Exploration Cohort C2A: Mona 750 mg Q2W + Durva + Cetu

Exploration Cohort C1B: Mona 750 mg Q2W + Cetu

Exploration Cohort C1A: Mona 750 mg Q2W + Durva + Cetu

Exploration Cohort C2B: Mona 750 mg Q2W + Cetu

Total subjects affected by serious adverse events

subjects affected / exposed

1 / 3 (33.33%)

0 / 3 (0.00%)

11 / 18 (61.11%)

10 / 18 (55.56%)

7 / 20 (35.00%)

1 / 3 (33.33%)

8 / 18 (44.44%)

4 / 18 (22.22%)

11 / 40 (27.50%)

16 / 40 (40.00%)

17 / 40 (42.50%)

9 / 44 (20.45%)

5 / 41 (12.20%)

10 / 40 (25.00%)

11 / 37 (29.73%)

number of deaths (all causes)

number of deaths resulting from adverse events

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

Cancer pain

subjects affected / exposed ^[1]

0 / 3 (0.00%)

0 / 18 (0.00%)

0 / 20 (0.00%)

0 / 3 (0.00%)

0 / 18 (0.00%)

0 / 40 (0.00%)

1 / 40 (2.50%)

0 / 40 (0.00%)

0 / 44 (0.00%)

0 / 41 (0.00%)

0 / 39 (0.00%)

0 / 37 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Myelofibrosis

subjects affected / exposed ^[2]

0 / 3 (0.00%)

0 / 18 (0.00%)

0 / 20 (0.00%)

0 / 3 (0.00%)

0 / 18 (0.00%)

0 / 40 (0.00%)

1 / 40 (2.50%)

0 / 40 (0.00%)

0 / 44 (0.00%)

0 / 41 (0.00%)

0 / 39 (0.00%)

0 / 37 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Vascular disorders

Embolism

subjects affected / exposed ^[3]

0 / 3 (0.00%)

0 / 18 (0.00%)

1 / 18 (5.56%)

0 / 20 (0.00%)

0 / 3 (0.00%)

0 / 18 (0.00%)

1 / 18 (5.56%)

0 / 40 (0.00%)

0 / 44 (0.00%)

0 / 41 (0.00%)

0 / 39 (0.00%)

0 / 37 (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

Lymphoedema

subjects affected / exposed ^[4]

0 / 3 (0.00%)

0 / 18 (0.00%)

0 / 20 (0.00%)

0 / 3 (0.00%)

1 / 18 (5.56%)

0 / 18 (0.00%)

0 / 40 (0.00%)

0 / 44 (0.00%)

0 / 41 (0.00%)

0 / 39 (0.00%)

0 / 37 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Hypotension

subjects affected / exposed ^[5]

0 / 3 (0.00%)

0 / 18 (0.00%)

0 / 20 (0.00%)

0 / 3 (0.00%)

0 / 18 (0.00%)

0 / 40 (0.00%)

0 / 44 (0.00%)

1 / 41 (2.44%)

0 / 39 (0.00%)

0 / 37 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Vena cava thrombosis

subjects affected / exposed ^[6]

0 / 3 (0.00%)

1 / 18 (5.56%)

0 / 18 (0.00%)

0 / 20 (0.00%)

0 / 3 (0.00%)

0 / 18 (0.00%)

0 / 40 (0.00%)

0 / 44 (0.00%)

0 / 41 (0.00%)

0 / 39 (0.00%)

0 / 37 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pelvic venous thrombosis

subjects affected / exposed ^[7]

0 / 3 (0.00%)

0 / 18 (0.00%)

0 / 20 (0.00%)

0 / 3 (0.00%)

0 / 18 (0.00%)

0 / 40 (0.00%)

0 / 44 (0.00%)

1 / 41 (2.44%)

0 / 39 (0.00%)

0 / 37 (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

Fatigue

subjects affected / exposed ^[8]

0 / 3 (0.00%)

0 / 18 (0.00%)

0 / 20 (0.00%)

0 / 3 (0.00%)

0 / 18 (0.00%)

0 / 40 (0.00%)

0 / 44 (0.00%)

0 / 41 (0.00%)

1 / 39 (2.56%)

0 / 37 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Hypothermia

subjects affected / exposed ^[9]

0 / 3 (0.00%)

0 / 18 (0.00%)

1 / 18 (5.56%)

0 / 20 (0.00%)

0 / 3 (0.00%)

0 / 18 (0.00%)

0 / 40 (0.00%)

0 / 44 (0.00%)

0 / 41 (0.00%)

0 / 39 (0.00%)

0 / 37 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Malaise

subjects affected / exposed ^[10]

0 / 3 (0.00%)

0 / 18 (0.00%)

1 / 18 (5.56%)

0 / 20 (0.00%)

0 / 3 (0.00%)

0 / 18 (0.00%)

0 / 40 (0.00%)

0 / 44 (0.00%)

0 / 41 (0.00%)

0 / 39 (0.00%)

0 / 37 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Multiple organ dysfunction syndrome

subjects affected / exposed ^[11]

0 / 3 (0.00%)

0 / 18 (0.00%)

0 / 20 (0.00%)

0 / 3 (0.00%)

0 / 18 (0.00%)

0 / 40 (0.00%)

1 / 44 (2.27%)

0 / 41 (0.00%)

0 / 39 (0.00%)

0 / 37 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

Non-cardiac chest pain

subjects affected / exposed ^[12]

0 / 3 (0.00%)

0 / 18 (0.00%)

0 / 20 (0.00%)

0 / 3 (0.00%)

0 / 18 (0.00%)

0 / 40 (0.00%)

0 / 44 (0.00%)

0 / 41 (0.00%)

0 / 39 (0.00%)

1 / 37 (2.70%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Oedema peripheral

subjects affected / exposed ^[13]

0 / 3 (0.00%)

0 / 18 (0.00%)

1 / 18 (5.56%)

0 / 20 (0.00%)

0 / 3 (0.00%)

0 / 18 (0.00%)

0 / 40 (0.00%)

0 / 44 (0.00%)

0 / 41 (0.00%)

0 / 39 (0.00%)

0 / 37 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pain

subjects affected / exposed ^[14]

0 / 3 (0.00%)

0 / 18 (0.00%)

0 / 20 (0.00%)

0 / 3 (0.00%)

0 / 18 (0.00%)

1 / 40 (2.50%)

0 / 40 (0.00%)

0 / 44 (0.00%)

0 / 41 (0.00%)

0 / 39 (0.00%)

0 / 37 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pyrexia

subjects affected / exposed ^[15]

0 / 3 (0.00%)

1 / 18 (5.56%)

0 / 18 (0.00%)

0 / 20 (0.00%)

0 / 3 (0.00%)

2 / 18 (11.11%)

1 / 18 (5.56%)

0 / 40 (0.00%)

1 / 40 (2.50%)

0 / 44 (0.00%)

0 / 41 (0.00%)

1 / 39 (2.56%)

0 / 37 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 2

0 / 1

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Systemic inflammatory response syndrome

subjects affected / exposed ^[16]

0 / 3 (0.00%)

0 / 18 (0.00%)

0 / 20 (0.00%)

0 / 3 (0.00%)

0 / 18 (0.00%)

0 / 40 (0.00%)

1 / 40 (2.50%)

0 / 40 (0.00%)

0 / 44 (0.00%)

0 / 41 (0.00%)

0 / 39 (0.00%)

0 / 37 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Immune system disorders

Anaphylactic shock

subjects affected / exposed ^[17]

0 / 3 (0.00%)

0 / 18 (0.00%)

1 / 20 (5.00%)

0 / 3 (0.00%)

0 / 18 (0.00%)

0 / 40 (0.00%)

0 / 44 (0.00%)

0 / 41 (0.00%)

0 / 39 (0.00%)

0 / 37 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Reproductive system and breast disorders

Intermenstrual bleeding

subjects affected / exposed ^[18]

0 / 3 (0.00%)

0 / 18 (0.00%)

0 / 20 (0.00%)

0 / 3 (0.00%)

1 / 18 (5.56%)

0 / 18 (0.00%)

0 / 40 (0.00%)

0 / 44 (0.00%)

0 / 41 (0.00%)

0 / 39 (0.00%)

0 / 37 (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

Acute respiratory failure

subjects affected / exposed ^[19]

0 / 3 (0.00%)

0 / 18 (0.00%)

0 / 20 (0.00%)

0 / 3 (0.00%)

0 / 18 (0.00%)

0 / 40 (0.00%)

1 / 44 (2.27%)

0 / 41 (0.00%)

0 / 39 (0.00%)

0 / 37 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Dyspnoea

subjects affected / exposed ^[20]

0 / 3 (0.00%)

0 / 18 (0.00%)

0 / 20 (0.00%)

0 / 3 (0.00%)

0 / 18 (0.00%)

1 / 40 (2.50%)

0 / 40 (0.00%)

0 / 44 (0.00%)

0 / 41 (0.00%)

0 / 39 (0.00%)

0 / 37 (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 ^[21]

0 / 3 (0.00%)

0 / 18 (0.00%)

1 / 20 (5.00%)

0 / 3 (0.00%)

0 / 18 (0.00%)

0 / 40 (0.00%)

0 / 44 (0.00%)

0 / 41 (0.00%)

0 / 39 (0.00%)

0 / 37 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Hypoxia

subjects affected / exposed ^[22]

0 / 3 (0.00%)

0 / 18 (0.00%)

0 / 20 (0.00%)

0 / 3 (0.00%)

0 / 18 (0.00%)

0 / 40 (0.00%)

0 / 44 (0.00%)

0 / 41 (0.00%)

0 / 39 (0.00%)

1 / 37 (2.70%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Pleural effusion

subjects affected / exposed ^[23]

0 / 3 (0.00%)

0 / 18 (0.00%)

0 / 20 (0.00%)

0 / 3 (0.00%)

2 / 18 (11.11%)

0 / 18 (0.00%)

1 / 40 (2.50%)

0 / 40 (0.00%)

2 / 40 (5.00%)

0 / 44 (0.00%)

0 / 41 (0.00%)

0 / 39 (0.00%)

0 / 37 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

0 / 1

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Pneumonitis

subjects affected / exposed ^[24]

0 / 3 (0.00%)

0 / 18 (0.00%)

1 / 20 (5.00%)

0 / 3 (0.00%)

0 / 18 (0.00%)

0 / 40 (0.00%)

0 / 44 (0.00%)

0 / 41 (0.00%)

0 / 39 (0.00%)

0 / 37 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pneumothorax

subjects affected / exposed ^[25]

0 / 3 (0.00%)

1 / 18 (5.56%)

0 / 20 (0.00%)

0 / 3 (0.00%)

0 / 18 (0.00%)

0 / 40 (0.00%)

0 / 44 (0.00%)

0 / 41 (0.00%)

0 / 39 (0.00%)

0 / 37 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Respiratory failure

subjects affected / exposed ^[26]

0 / 3 (0.00%)

1 / 18 (5.56%)

0 / 18 (0.00%)

0 / 20 (0.00%)

0 / 3 (0.00%)

0 / 18 (0.00%)

0 / 40 (0.00%)

1 / 40 (2.50%)

0 / 44 (0.00%)

0 / 41 (0.00%)

0 / 39 (0.00%)

0 / 37 (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

Pulmonary embolism

subjects affected / exposed ^[27]

0 / 3 (0.00%)

1 / 18 (5.56%)

0 / 18 (0.00%)

0 / 20 (0.00%)

0 / 3 (0.00%)

0 / 18 (0.00%)

0 / 40 (0.00%)

1 / 40 (2.50%)

0 / 44 (0.00%)

1 / 41 (2.44%)

0 / 39 (0.00%)

1 / 37 (2.70%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Psychiatric disorders

Bipolar disorder

subjects affected / exposed ^[28]

0 / 3 (0.00%)

0 / 18 (0.00%)

0 / 20 (0.00%)

0 / 3 (0.00%)

0 / 18 (0.00%)

0 / 40 (0.00%)

1 / 40 (2.50%)

0 / 44 (0.00%)

0 / 41 (0.00%)

0 / 39 (0.00%)

0 / 37 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

Investigations

Transaminases increased

subjects affected / exposed ^[29]

0 / 3 (0.00%)

0 / 18 (0.00%)

0 / 20 (0.00%)

0 / 3 (0.00%)

0 / 18 (0.00%)

0 / 40 (0.00%)

0 / 44 (0.00%)

0 / 41 (0.00%)

1 / 39 (2.56%)

0 / 37 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Platelet count decreased

subjects affected / exposed ^[30]

0 / 3 (0.00%)

0 / 18 (0.00%)

0 / 20 (0.00%)

0 / 3 (0.00%)

0 / 18 (0.00%)

0 / 40 (0.00%)

0 / 44 (0.00%)

0 / 41 (0.00%)

0 / 39 (0.00%)

1 / 37 (2.70%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Injury, poisoning and procedural complications

Lower limb fracture

subjects affected / exposed ^[31]

0 / 3 (0.00%)

0 / 18 (0.00%)

1 / 18 (5.56%)

0 / 20 (0.00%)

0 / 3 (0.00%)

0 / 18 (0.00%)

0 / 40 (0.00%)

0 / 44 (0.00%)

0 / 41 (0.00%)

0 / 39 (0.00%)

0 / 37 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Infusion related reaction

subjects affected / exposed ^[32]

0 / 3 (0.00%)

0 / 18 (0.00%)

0 / 20 (0.00%)

0 / 3 (0.00%)

0 / 18 (0.00%)

0 / 40 (0.00%)

1 / 40 (2.50%)

0 / 44 (0.00%)

0 / 41 (0.00%)

0 / 39 (0.00%)

0 / 37 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pelvic fracture

subjects affected / exposed ^[33]

0 / 3 (0.00%)

0 / 18 (0.00%)

0 / 20 (0.00%)

0 / 3 (0.00%)

0 / 18 (0.00%)

0 / 40 (0.00%)

1 / 40 (2.50%)

0 / 44 (0.00%)

0 / 41 (0.00%)

0 / 39 (0.00%)

0 / 37 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Post procedural complication

subjects affected / exposed ^[34]

0 / 3 (0.00%)

0 / 18 (0.00%)

0 / 20 (0.00%)

0 / 3 (0.00%)

0 / 18 (0.00%)

0 / 40 (0.00%)

1 / 40 (2.50%)

0 / 40 (0.00%)

0 / 44 (0.00%)

0 / 41 (0.00%)

0 / 39 (0.00%)

0 / 37 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Cardiac disorders

Acute myocardial infarction

subjects affected / exposed ^[35]

0 / 3 (0.00%)

0 / 18 (0.00%)

0 / 20 (0.00%)

0 / 3 (0.00%)

0 / 18 (0.00%)

0 / 40 (0.00%)

1 / 40 (2.50%)

0 / 44 (0.00%)

0 / 41 (0.00%)

0 / 39 (0.00%)

0 / 37 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Atrial fibrillation

subjects affected / exposed ^[36]

0 / 3 (0.00%)

1 / 18 (5.56%)

0 / 18 (0.00%)

0 / 20 (0.00%)

0 / 3 (0.00%)

0 / 18 (0.00%)

0 / 40 (0.00%)

0 / 44 (0.00%)

0 / 41 (0.00%)

0 / 39 (0.00%)

0 / 37 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Atrial flutter

subjects affected / exposed ^[37]

0 / 3 (0.00%)

0 / 18 (0.00%)

1 / 18 (5.56%)

0 / 20 (0.00%)

0 / 3 (0.00%)

0 / 18 (0.00%)

0 / 40 (0.00%)

0 / 44 (0.00%)

0 / 41 (0.00%)

0 / 39 (0.00%)

0 / 37 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Myocarditis

subjects affected / exposed ^[38]

0 / 3 (0.00%)

0 / 18 (0.00%)

0 / 20 (0.00%)

0 / 3 (0.00%)

1 / 18 (5.56%)

0 / 18 (0.00%)

0 / 40 (0.00%)

1 / 44 (2.27%)

0 / 41 (0.00%)

0 / 39 (0.00%)

0 / 37 (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

Myocardial ischaemia

subjects affected / exposed ^[39]

0 / 3 (0.00%)

0 / 18 (0.00%)

1 / 20 (5.00%)

0 / 3 (0.00%)

0 / 18 (0.00%)

0 / 40 (0.00%)

0 / 44 (0.00%)

0 / 41 (0.00%)

0 / 39 (0.00%)

0 / 37 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pericarditis

subjects affected / exposed ^[40]

0 / 3 (0.00%)

0 / 18 (0.00%)

0 / 20 (0.00%)

0 / 3 (0.00%)

1 / 18 (5.56%)

0 / 18 (0.00%)

0 / 40 (0.00%)

0 / 44 (0.00%)

0 / 41 (0.00%)

0 / 39 (0.00%)

0 / 37 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Nervous system disorders

Encephalitis autoimmune

subjects affected / exposed ^[41]

0 / 3 (0.00%)

0 / 18 (0.00%)

0 / 20 (0.00%)

0 / 3 (0.00%)

0 / 18 (0.00%)

0 / 40 (0.00%)

1 / 40 (2.50%)

0 / 44 (0.00%)

0 / 41 (0.00%)

0 / 39 (0.00%)

0 / 37 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Encephalopathy

subjects affected / exposed ^[42]

0 / 3 (0.00%)

0 / 18 (0.00%)

1 / 18 (5.56%)

0 / 20 (0.00%)

0 / 3 (0.00%)

0 / 18 (0.00%)

0 / 40 (0.00%)

0 / 44 (0.00%)

0 / 41 (0.00%)

0 / 39 (0.00%)

0 / 37 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Metabolic encephalopathy

subjects affected / exposed ^[43]

0 / 3 (0.00%)

0 / 18 (0.00%)

0 / 20 (0.00%)

0 / 3 (0.00%)

0 / 18 (0.00%)

0 / 40 (0.00%)

1 / 44 (2.27%)

0 / 41 (0.00%)

0 / 39 (0.00%)

0 / 37 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Paraesthesia

subjects affected / exposed ^[44]

0 / 3 (0.00%)

0 / 18 (0.00%)

0 / 20 (0.00%)

0 / 3 (0.00%)

0 / 18 (0.00%)

0 / 40 (0.00%)

0 / 44 (0.00%)

1 / 41 (2.44%)

0 / 39 (0.00%)

0 / 37 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Seizure

subjects affected / exposed ^[45]

0 / 3 (0.00%)

1 / 18 (5.56%)

0 / 18 (0.00%)

0 / 20 (0.00%)

0 / 3 (0.00%)

0 / 18 (0.00%)

0 / 40 (0.00%)

0 / 44 (0.00%)

0 / 41 (0.00%)

0 / 39 (0.00%)

0 / 37 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Transient ischaemic attack

subjects affected / exposed ^[46]

0 / 3 (0.00%)

1 / 18 (5.56%)

0 / 18 (0.00%)

0 / 20 (0.00%)

0 / 3 (0.00%)

0 / 18 (0.00%)

0 / 40 (0.00%)

0 / 44 (0.00%)

0 / 41 (0.00%)

0 / 39 (0.00%)

0 / 37 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Blood and lymphatic system disorders

Anaemia

subjects affected / exposed ^[47]

0 / 3 (0.00%)

0 / 18 (0.00%)

0 / 20 (0.00%)

0 / 3 (0.00%)

0 / 18 (0.00%)

1 / 18 (5.56%)

0 / 40 (0.00%)

0 / 44 (0.00%)

0 / 41 (0.00%)

0 / 39 (0.00%)

0 / 37 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Febrile neutropenia

subjects affected / exposed ^[48]

0 / 3 (0.00%)

1 / 18 (5.56%)

2 / 18 (11.11%)

0 / 20 (0.00%)

0 / 3 (0.00%)

0 / 18 (0.00%)

0 / 40 (0.00%)

0 / 44 (0.00%)

0 / 41 (0.00%)

0 / 39 (0.00%)

0 / 37 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Gastrointestinal disorders

Abdominal pain

subjects affected / exposed ^[49]

0 / 3 (0.00%)

0 / 18 (0.00%)

0 / 20 (0.00%)

1 / 3 (33.33%)

0 / 18 (0.00%)

1 / 40 (2.50%)

2 / 40 (5.00%)

1 / 44 (2.27%)

0 / 41 (0.00%)

1 / 39 (2.56%)

3 / 37 (8.11%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

0 / 1

0 / 3

0 / 1

0 / 0

0 / 1

0 / 3

deaths causally related to treatment / all

0 / 0

Abdominal pain upper

subjects affected / exposed ^[50]

0 / 3 (0.00%)

0 / 18 (0.00%)

0 / 20 (0.00%)

0 / 3 (0.00%)

0 / 18 (0.00%)

0 / 40 (0.00%)

0 / 44 (0.00%)

1 / 41 (2.44%)

0 / 39 (0.00%)

0 / 37 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Abdominal pain lower

subjects affected / exposed ^[51]

0 / 3 (0.00%)

0 / 18 (0.00%)

0 / 20 (0.00%)

0 / 3 (0.00%)

0 / 18 (0.00%)

0 / 40 (0.00%)

0 / 44 (0.00%)

0 / 41 (0.00%)

0 / 39 (0.00%)

1 / 37 (2.70%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Ascites

subjects affected / exposed ^[52]

0 / 3 (0.00%)

0 / 18 (0.00%)

0 / 20 (0.00%)

1 / 3 (33.33%)

0 / 18 (0.00%)

1 / 40 (2.50%)

0 / 44 (0.00%)

0 / 41 (0.00%)

1 / 39 (2.56%)

0 / 37 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Colitis

subjects affected / exposed ^[53]

0 / 3 (0.00%)

0 / 18 (0.00%)

0 / 20 (0.00%)

0 / 3 (0.00%)

0 / 18 (0.00%)

0 / 40 (0.00%)

2 / 40 (5.00%)

0 / 40 (0.00%)

0 / 44 (0.00%)

0 / 41 (0.00%)

0 / 39 (0.00%)

0 / 37 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Colonic fistula

subjects affected / exposed ^[54]

0 / 3 (0.00%)

0 / 18 (0.00%)

1 / 18 (5.56%)

0 / 20 (0.00%)

0 / 3 (0.00%)

0 / 18 (0.00%)

0 / 40 (0.00%)

0 / 44 (0.00%)

0 / 41 (0.00%)

0 / 39 (0.00%)

0 / 37 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Constipation

subjects affected / exposed ^[55]

0 / 3 (0.00%)

0 / 18 (0.00%)

0 / 20 (0.00%)

0 / 3 (0.00%)

1 / 18 (5.56%)

0 / 18 (0.00%)

0 / 40 (0.00%)

1 / 44 (2.27%)

0 / 41 (0.00%)

0 / 39 (0.00%)

0 / 37 (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

Diarrhoea

subjects affected / exposed ^[56]

0 / 3 (0.00%)

0 / 18 (0.00%)

0 / 20 (0.00%)

0 / 3 (0.00%)

0 / 18 (0.00%)

0 / 40 (0.00%)

1 / 40 (2.50%)

0 / 40 (0.00%)

0 / 44 (0.00%)

0 / 41 (0.00%)

0 / 39 (0.00%)

0 / 37 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Gastritis

subjects affected / exposed ^[57]

0 / 3 (0.00%)

0 / 18 (0.00%)

0 / 20 (0.00%)

0 / 3 (0.00%)

0 / 18 (0.00%)

1 / 40 (2.50%)

0 / 40 (0.00%)

0 / 44 (0.00%)

0 / 41 (0.00%)

0 / 39 (0.00%)

0 / 37 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Gastrointestinal fistula

subjects affected / exposed ^[58]

0 / 3 (0.00%)

1 / 18 (5.56%)

0 / 18 (0.00%)

0 / 20 (0.00%)

0 / 3 (0.00%)

0 / 18 (0.00%)

0 / 40 (0.00%)

0 / 44 (0.00%)

0 / 41 (0.00%)

0 / 39 (0.00%)

0 / 37 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Gastrointestinal haemorrhage

subjects affected / exposed ^[59]

0 / 3 (0.00%)

0 / 18 (0.00%)

0 / 20 (0.00%)

0 / 3 (0.00%)

0 / 18 (0.00%)

1 / 18 (5.56%)

0 / 40 (0.00%)

0 / 44 (0.00%)

0 / 41 (0.00%)

0 / 39 (0.00%)

0 / 37 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Ileus

subjects affected / exposed ^[60]

0 / 3 (0.00%)

1 / 18 (5.56%)

0 / 18 (0.00%)

0 / 20 (0.00%)

0 / 3 (0.00%)

0 / 18 (0.00%)

0 / 40 (0.00%)

0 / 44 (0.00%)

0 / 41 (0.00%)

0 / 39 (0.00%)

0 / 37 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Haematochezia

subjects affected / exposed ^[61]

1 / 3 (33.33%)

0 / 3 (0.00%)

0 / 18 (0.00%)

0 / 20 (0.00%)

0 / 3 (0.00%)

0 / 18 (0.00%)

0 / 40 (0.00%)

0 / 44 (0.00%)

0 / 41 (0.00%)

0 / 39 (0.00%)

0 / 37 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Intestinal obstruction

subjects affected / exposed ^[62]

0 / 3 (0.00%)

1 / 18 (5.56%)

0 / 18 (0.00%)

0 / 20 (0.00%)

0 / 3 (0.00%)

0 / 18 (0.00%)

1 / 18 (5.56%)

0 / 40 (0.00%)

3 / 40 (7.50%)

1 / 40 (2.50%)

1 / 44 (2.27%)

0 / 41 (0.00%)

0 / 39 (0.00%)

0 / 37 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 3

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Large intestine perforation

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials

Clinical Trial Results: A Phase 1/2 Study of Durvalumab and Monalizumab in Adult Subjects with Select Advanced Solid Tumors

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)

Primary: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)

Primary: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)

Primary: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)

Primary: Change From Baseline in Respiratory Rate (RR)

Primary: Change From Baseline in Respiratory Rate (RR)

Primary: Change From Baseline in Pulse Rate (PR)

Primary: Change From Baseline in Pulse Rate (PR)

Primary: Change From Baseline in Body Temperature (BT)

Primary: Change From Baseline in Body Temperature (BT)

Primary: Change From Baseline in Oxygen Saturation (OS)

Primary: Change From Baseline in Oxygen Saturation (OS)

Primary: Number of Participants With Notable Change in QTcF and QTcB From Baseline

Primary: Number of Participants With Notable Change in QTcF and QTcB From Baseline

Primary: Number of Participants With at Least 2-Grade Shift From Baseline in Laboratory Parameters

Primary: Number of Participants With at Least 2-Grade Shift From Baseline in Laboratory Parameters

Primary: Number of Participants With Dose Limiting Toxicities (DLTs)

Primary: Number of Participants With Dose Limiting Toxicities (DLTs)

Primary: Percentage of Participants With Objective Response (OR) in Exploration Cohorts C1A and C1B

Primary: Percentage of Participants With Objective Response (OR) in Exploration Cohorts C1A and C1B

Secondary: Percentage of Participants With OR

Secondary: Percentage of Participants With OR

Secondary: Percentage of Participants With OR in Exploration Cohorts C2A and C2B

Secondary: Percentage of Participants With OR in Exploration Cohorts C2A and C2B

Secondary: Percentage of Participants with Disease Control (DC)

Secondary: Percentage of Participants with Disease Control (DC)

Secondary: Percentage of Participants with DC in Exploration Cohorts (C1A, C1B, C2A, and C2B)

Secondary: Percentage of Participants with DC in Exploration Cohorts (C1A, C1B, C2A, and C2B)

Secondary: Duration of Response (DoR)

Secondary: Duration of Response (DoR)

Secondary: DoR in Exploration Cohorts (C1A, C1B, C2A, and C2B)

Secondary: DoR in Exploration Cohorts (C1A, C1B, C2A, and C2B)

Secondary: Progression-Free Survival (PFS)

Secondary: Progression-Free Survival (PFS)

Secondary: Progression-Free Survival (PFS) in Exploration Cohorts (C1A, C1B, C2A, and C2B)

Secondary: Progression-Free Survival (PFS) in Exploration Cohorts (C1A, C1B, C2A, and C2B)

Secondary: Overall Survival

Secondary: Overall Survival

Secondary: Overall Survival in Exploration Cohorts (C1A, C1B, C2A, and C2B)

Secondary: Overall Survival in Exploration Cohorts (C1A, C1B, C2A, and C2B)

Secondary: Maximum Observed Serum Concentration (Cmax) of Monalizumab

Secondary: Maximum Observed Serum Concentration (Cmax) of Monalizumab

Secondary: Minimum Observed Serum Concentration (Cmin) of Monalizumab

Secondary: Minimum Observed Serum Concentration (Cmin) of Monalizumab

Secondary: Serum Concentration of Durvalumab

Secondary: Serum Concentration of Durvalumab

Secondary: Serum Concentration of Cetuximab

Secondary: Serum Concentration of Cetuximab

Secondary: Number of Participants With Positive Anti-Drug Antibodies (ADA) to Monalizumab

Secondary: Number of Participants With Positive Anti-Drug Antibodies (ADA) to Monalizumab

Secondary: Number of Participants With Positive ADA to Durvalumab

Secondary: Number of Participants With Positive ADA to Durvalumab

Secondary: Number of Participants With Positive ADA to Cetuximab

Secondary: Number of Participants With Positive ADA to Cetuximab

Secondary: Number of Participants With Programmed Death Ligand 1 (PD-L1) Expression in Pretreatment Tumor Biopsies

Secondary: Number of Participants With Programmed Death Ligand 1 (PD-L1) Expression in Pretreatment Tumor Biopsies

Secondary: Number of Participants With Human Leukocyte Antigen (HLA)-E Expression in Pretreatment Tumor Biopsies

Secondary: Number of Participants With Human Leukocyte Antigen (HLA)-E Expression in Pretreatment Tumor Biopsies

Adverse events

Clinical Trial Results:
A Phase 1/2 Study of Durvalumab and Monalizumab in Adult Subjects with Select Advanced Solid Tumors