Download PDF

Clinical Trial Results:
A Single-Arm, Multicenter, Phase 1b Study with an Expansion Cohort to Evaluate Safety and Efficacy of Necitumumab in Combination with Abemaciclib in Treatment of Patients with Stage IV Non-Small Cell Lung Cancer (NSCLC)

Summary
EudraCT number	2014-005042-21
Trial protocol	BE ES
Global end of trial date	28 May 2019

Results information
Results version number	v2(current)
This version publication date	24 Feb 2021
First version publication date	07 Jun 2020
Other versions	v1
Version creation reason	Correction of full data set Copy Correction to full data set

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

Collapse all Expand all

Trial information

Top of page

Sponsor protocol code

I4X-MC-JFCU

ISRCTN number

US NCT number

NCT02411591

WHO universal trial number (UTN)

Other trial identifiers

Trial Number: 15573

Sponsor organisation name

Eli Lilly and Company

Sponsor organisation address

Lilly Corporate Center, Indianapolis, IN, United States, 46285

Public contact

Available Mon ‐ Fri 9 AM ‐ 5 PM EST, Eli Lilly and Company, 1 877‐CTLilly,

Scientific contact

Available Mon ‐ Fri 9 AM ‐ 5 PM EST, Eli Lilly and Company, 1 877‐285‐4559,

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

28 May 2019

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

28 May 2019

Was the trial ended prematurely?

Main objective of the trial

This is medical research evaluating the safety and efficacy of two new medicines (necitumumab and abemaciclib), administered in combination in participants affected by a defined type of advanced lung cancer (stage IV non-small-cell lung cancer).

Protection of trial subjects

This study was conducted in accordance with International Conference on Harmonization (ICH) Good Clinical Practice, and the principles of the Declaration of Helsinki, in addition to following the laws and regulations of the country or countries in which a study is conducted.

Background therapy

Evidence for comparator

Actual start date of recruitment

04 Jun 2015

Long term follow-up planned

Yes

Long term follow-up rationale

Safety, Efficacy

Long term follow-up duration

24 Months

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

Belgium: 11

Country: Number of subjects enrolled

France: 52

Country: Number of subjects enrolled

Spain: 3

Worldwide total number of subjects

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)

From 65 to 84 years

85 years and over

Subject disposition

Top of page

Recruitment details

No Text Available

Screening details

The study has 2 parts (Part A and Part B). Part A is a dose-escalation study to determine the recommended dose of abemaciclib in combination with necitumumab Part B (expansion cohort). Completers completed the 2 cycles, with required assessment, had progressive disease or died due to any cause, alive and on study at conclusion but off treatment.

Period 1 title

Overall Study (overall period)

Is this the baseline period?

Yes

Allocation method

Non-randomised - controlled

Blinding used

Not blinded

Are arms mutually exclusive

Yes

Cohort 1 (Necitumumab 800 mg + Abemaciclib 100 mg)

Arm description

Part A: Necitumumab 800 milligram (mg) was administered IV on Days 1 and 8, followed by abemaciclib 100 mg given orally every 12 hours on Days 1 to 21. (21 day cycles.) Treatment may continue until discontinuation criterion is met.

Arm type

Experimental

Investigational medicinal product name

Necitumumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Necitumumab 800 milligram (mg) was administered intravenously (IV) on Days 1 and 8.

Investigational medicinal product name

Abemaciclib

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

abemaciclib 100 mg given orally every 12 hours on Days 1 to 21.

Cohort 2 (Necitumumab 800 mg + Abemaciclib 150 mg)

Arm description

Part A: Necitumumab 800 mg administered intravenously (IV) on Days 1 and 8, followed by abemaciclib 150 mg given orally every 12 hours on Days 1 to 21. (21 day cycles.) Treatment may continue until discontinuation criterion is met. Part B: (expansion cohort): Necitumumab 800 mg administered IV on Days 1 and 8, followed by abemaciclib 150 mg given orally every 12 hours on Days 1 to 21. (21 day cycles.) Treatment may continue until discontinuation criterion is met.

Arm type

Experimental

Investigational medicinal product name

Necitumumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Necitumumab administered intravenously (IV) on Days 1 and 8, followed by abemaciclib given orally every 12 hours on Days 1 to 21. (21 day cycles.)

Investigational medicinal product name

Abemaciclib

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

abemaciclib 150 mg given orally every 12 hours on Days 1 to 21.

Cohort 3 (Necitumumab 800 mg + Abemaciclib 200 mg)

Arm description

Part A: Necitumumab 800 mg was administered IV on Days 1 and 8, followed by abemaciclib 200 mg given orally every 12 hours on Days 1 to 21. (21 day cycles.) Treatment may continue until discontinuation criterion is met.

Arm type

Experimental

Investigational medicinal product name

Necitumumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Necitumumab 800 mg was administered IV on Days 1 and 8.

Investigational medicinal product name

Abemaciclib

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

abemaciclib 200 mg given orally every 12 hours on Days 1 to 21.

Number of subjects in period 1	Cohort 1 (Necitumumab 800 mg + Abemaciclib 100 mg)	Cohort 2 (Necitumumab 800 mg + Abemaciclib 150 mg)	Cohort 3 (Necitumumab 800 mg + Abemaciclib 200 mg)
Started	3	57	6
Part A	3	6 ^[1]	6
Expansion Cohort Part B	0 ^[2]	51	0 ^[3]
Progressive Disease	3	42 ^[4]	3
Death	0 ^[5]	2 ^[6]	0 ^[7]
Completed	3	47	3
Not completed	0	10	3
Consent withdrawn by subject	-	3	-
Physician decision	-	3	1
Adverse event, non-fatal	-	4	2

Notes
[1] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: The number of participants at each milestone is a subset analysis population to the overall number of participants in the arm.
[2] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: The number of participants at each milestone is a subset analysis population to the overall number of participants in the arm.
[3] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: The number of participants at each milestone is a subset analysis population to the overall number of participants in the arm.
[4] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: The number of participants at each milestone is a subset analysis population to the overall number of participants in the arm.
[5] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: The number of participants at each milestone is a subset analysis population to the overall number of participants in the arm.
[6] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: The number of participants at each milestone is a subset analysis population to the overall number of participants in the arm.
[7] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: The number of participants at each milestone is a subset analysis population to the overall number of participants in the arm.

Baseline characteristics

Top of page

Reporting group title

Cohort 1 (Necitumumab 800 mg + Abemaciclib 100 mg)

Reporting group description

Reporting group title

Cohort 2 (Necitumumab 800 mg + Abemaciclib 150 mg)

Reporting group description

Reporting group title

Cohort 3 (Necitumumab 800 mg + Abemaciclib 200 mg)

Reporting group description

Reporting group values	Cohort 1 (Necitumumab 800 mg + Abemaciclib 100 mg)	Cohort 2 (Necitumumab 800 mg + Abemaciclib 150 mg)	Cohort 3 (Necitumumab 800 mg + Abemaciclib 200 mg)	Total
Number of subjects	3	57	6	66
Age categorical
Units: Subjects
Age continuous
Units: years
arithmetic mean (standard deviation)	62.33 ( 2.31 )	61.42 ( 10.58 )	49.00 ( 7.59 )	-
Gender categorical
Units: Subjects
Female	1	17	1	19
Male	2	40	5	47
Ethnicity (NIH/OMB)
Units: Subjects
Hispanic or Latino	0	2	0	2
Not Hispanic or Latino	1	13	1	15
Unknown or Not Reported	2	42	5	49
Race (NIH/OMB)
Units: Subjects
American Indian or Alaska Native	0	0	0	0
Asian	0	0	0	0
Native Hawaiian or Other Pacific Islander	0	0	0	0
Black or African American	0	0	0	0
White	1	16	1	18
More than one race	0	0	0	0
Unknown or Not Reported	2	41	5	48
Region of Enrollment
Units: Subjects
Belgium	1	9	1	11
France	2	45	5	52
Spain	0	3	0	3

End points

Top of page

Reporting group title

Cohort 1 (Necitumumab 800 mg + Abemaciclib 100 mg)

Reporting group description

Reporting group title

Cohort 2 (Necitumumab 800 mg + Abemaciclib 150 mg)

Reporting group description

Reporting group title

Cohort 3 (Necitumumab 800 mg + Abemaciclib 200 mg)

Reporting group description

Subject analysis set title

Cohort 3 (Necitumamab 800 mg + Abemaciclib 200 mg)

Subject analysis set type

Per protocol

Subject analysis set description

Subject analysis set title

Total Enrolled Participants (Necitumumab + Abemaciclib)

Subject analysis set type

Per protocol

Subject analysis set description

Cohorts 1, 2 and 3 combined. Necitumumab 800 mg was administered IV on Days 1 and 8, followed by abemaciclib 100 mg, 150 mg or 200 mg given orally every 12 hours on Days 1 to 21. (21 day cycles.) Treatment may continue until discontinuation criterion is met.

Subject analysis set title

Necitumumab

Subject analysis set type

Per protocol

Subject analysis set description

Necitumumab 800 mg was administered IV on Days 1 and 8, of a 3-week cycle.

Subject analysis set title

Abemaciclib 100 mg

Subject analysis set type

Per protocol

Subject analysis set description

Necitumumab 800 mg administered IV on Days 1 and 8 followed by abemaciclib 100 mg given orally every 12 hours on Days 1 to 21. (21 day cycles.) Treatment may continue until discontinuation criterion is met.

Subject analysis set title

Abemaciclib 150 mg

Subject analysis set type

Per protocol

Subject analysis set description

Necitumumab 800 mg administered IV on Days 1 and 8 followed by abemaciclib 150 mg given orally every 12 hours on Days 1 to 21. (21 day cycles.) Treatment may continue until discontinuation criterion is met.

Subject analysis set title

Abemaciclib 200 mg

Subject analysis set type

Per protocol

Subject analysis set description

Necitumumab 800 mg administered IV on Days 1 and 8 followed by abemaciclib 200 mg given orally every 12 hours on Days 1 to 21. (21 day cycles.) Treatment may continue until discontinuation criterion is met.

Subject analysis set title

Cohort 1 (Necitumumab 800 mg + Abemaciclib 100 mg)

Subject analysis set type

Per protocol

Subject analysis set description

Part A: Necitumumab 800 mg was administered IV on Days 1 and 8, followed by abemaciclib 100 mg given orally every 12 hours on Days 1 to 21. (21 day cycles.) Treatment may continue until discontinuation criterion is met.

Subject analysis set title

Cohort 2 (Necitumumab 800 mg + Abemaciclib 150 mg)

Subject analysis set type

Sub-group analysis

Subject analysis set description

Part A: Necitumumab 800 mg was administered IV on Days 1 and 8, followed by abemaciclib 150 mg given orally every 12 hours on Days 1 to 21. (21 day cycles.)

Primary: Part A: Number of Participants with Abemaciclib Dose Limiting Toxicities (DLTs)

Top of page

End point title

Part A: Number of Participants with Abemaciclib Dose Limiting Toxicities (DLTs) ^[1]

End point description

A DLT was defined as one of the following adverse events (AEs), occurring in Cycle 1 if considered to be definitely, probably, or possibly related to necitumumab and abemaciclib: Grade 3 or 4 nonhematologic toxicity according to the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 (NCI-CTCAE v4.0), except for nausea, vomiting, diarrhea, or electrolyte disturbance. Grade 3 or 4 nausea, vomiting, or diarrhea that persists more than 2 days despite maximal supportive intervention. Grade 3 thrombocytopenia with bleeding requiring transfusion. Grade 4 thrombocytopenia with or without bleeding. Grade 4 neutropenia that persists more than 5 days.

End point type

Primary

End point timeframe

Baseline through Cycle 1 (Up to 21 Days)

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: DLT endpoint was summarized using descriptive statistics.

End point values	Cohort 3 (Necitumamab 800 mg + Abemaciclib 200 mg)	Cohort 1 (Necitumumab 800 mg + Abemaciclib 100 mg)	Cohort 2 (Necitumumab 800 mg + Abemaciclib 150 mg)
Number of subjects analysed	3 ^[2]	6 ^[3]	6 ^[4]
Units: participants	0	1	3

Notes
[2] - All participants who received at least one dose of study drug and had evaluable DLTs.
[3] - All participants who received at least one dose of study drug and had evaluable DLTs.
[4] - All participants who received at least one dose of study drug and had evaluable DLTs.

No statistical analyses for this end point

Primary: Progression Free Survival (PFS) Rate at 3 Months (Percentage of Participants with PFS at 3 Months)

Top of page

End point title

Progression Free Survival (PFS) Rate at 3 Months (Percentage of Participants with PFS at 3 Months) ^[5]

End point description

PFS defined as time from baseline until first radiographic documentation of measured progressive disease(PD) defined by response evaluation criteria in solid tumors (RECIST) v1.1 or death from any cause.PD was at least 20% increase in sum of diameters of target lesions with reference being smallest sum on study and an absolute increase of at least 5 millimeter (mm) or unequivocal progression of non-target lesions,or 1 or more new lesions.If participant does not have complete baseline disease assessment,PFS time censored at date of randomization,regardless of whether or not objectively determined disease progression or death observed for participant.If participant was not known to have died or have objective progression as of data inclusion cutoff date for analysis, the PFS time censored at last adequate tumor assessment date. The use of new anticancer therapy prior to occurrence of PD resulted in censoring at the date of last radiographic assessment prior to initiation of new therapy.

End point type

Primary

End point timeframe

Baseline to measured progressive disease or death due to any cause (3 Months)

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: PFS endpoint was summarized using descriptive statistics.

End point values	Cohort 1 (Necitumumab 800 mg + Abemaciclib 100 mg)	Cohort 2 (Necitumumab 800 mg + Abemaciclib 150 mg)	Cohort 3 (Necitumumab 800 mg + Abemaciclib 200 mg)
Number of subjects analysed	3 ^[6]	57 ^[7]	6 ^[8]
Units: Percentage of Participants
number (confidence interval 95%)	66.7 (5.4 to 94.5)	32.3 (20.4 to 44.8)	50.0 (11.1 to 80.4)

Notes
[6] - All enrolled participants who received at least one dose of study drug and had evaluable PFS data.
[7] - All enrolled participants who received at least one dose of study drug and had evaluable PFS data.
[8] - All enrolled participants who received at least one dose of study drug and had evaluable PFS data.

No statistical analyses for this end point

Secondary: Percentage of Participants Who Achieve Best Overall Tumor Response of Complete or Partial Response (Objective Response Rate [ORR])

Top of page

End point title

Percentage of Participants Who Achieve Best Overall Tumor Response of Complete or Partial Response (Objective Response Rate [ORR])

End point description

ORR was the percentage of participants achieving a best overall response of complete response (CR) or partial response (PR) as per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. CR defined as the disappearance of all target and non-target lesions and no appearance of new lesions. PR defined as at least a 30% decrease in the sum of the longest diameters (LD) of target lesions (taking as reference the baseline sum LD), no progression of nontarget lesions, and no appearance of new lesions. PD was at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions. Confidence intervals are based on Clopper-Pearson method.

End point type

Secondary

End point timeframe

Baseline to measured progressive disease or start of new anti-cancer therapy (up to 21 months)

End point values	Cohort 1 (Necitumumab 800 mg + Abemaciclib 100 mg)	Cohort 2 (Necitumumab 800 mg + Abemaciclib 150 mg)	Cohort 3 (Necitumumab 800 mg + Abemaciclib 200 mg)	Total Enrolled Participants (Necitumumab + Abemaciclib)
Number of subjects analysed	3 ^[9]	57 ^[10]	6 ^[11]	66 ^[12]
Units: percentage of participants
number (confidence interval 95%)
Overall Response Rate	66.7 (9.4 to 99.2)	5.3 (1.1 to 14.6)	0.0 (0.0 to 45.9)	7.6 (2.5 to 16.8)
PR	66.7 (9.4 to 99.2)	5.3 (1.1 to 14.6)	0.0 (0.0 to 45.9)	7.6 (2.5 to 16.8)
SD	33.3 (0.8 to 90.6)	42.1 (29.1 to 55.9)	66.7 (22.3 to 95.7)	43.9 (31.7 to 56.7)
PD	0.0 (0.0 to 70.8)	47.4 (34.0 to 61.0)	16.7 (0.4 to 64.1)	42.4 (30.3 to 55.2)

Notes
[9] - All enrolled participants who received at least one dose of study drug and had evaluable ORR data.
[10] - All enrolled participants who received at least one dose of study drug and had evaluable ORR data.
[11] - All enrolled participants who received at least one dose of study drug and had evaluable ORR data.
[12] - All enrolled participants who received at least one dose of study drug and had evaluable ORR data.

No statistical analyses for this end point

Secondary: Pharmacokinetics (PK): Predose Concentration (Cmin) of Necitumumab

Top of page

End point title

Pharmacokinetics (PK): Predose Concentration (Cmin) of Necitumumab

End point description

Predose necitumumab concentration data following doses of 800 mg administered Day 1 and 8 of a 3-week cycle as an intravenous (IV) infusion over 60 minutes.

End point type

Secondary

End point timeframe

Cycle 1, Day 8 (C1D8) and C2,3,5,7 D1: Predose

End point values	Necitumumab
Number of subjects analysed	61 ^[13]
Units: microgram/milliliter (μg/mL)
geometric mean (standard deviation)
Cycle 1, Day 8	64.1 ( 43.1 )
Cycle 2, Day 1	49.6 ( 63.8 )
Cycle 3, Day 1	93.8 ( 44.1 )
Cycle 5, Day 1	160 ( 50.3 )
Cycle 7, Day 1	165 ( 42.1 )

Notes
[13] - All participants who received at least one dose of necitumumab and had evaluable PK data.

No statistical analyses for this end point

Secondary: Pharmacokinetics (PK): Maximum Concentration (Cmax) of Necitumumab

Top of page

End point title

Pharmacokinetics (PK): Maximum Concentration (Cmax) of Necitumumab

End point description

Maximum necitumumab concentration data following doses of 800 mg administered Day 1 and 8 of a 3-week cycle as an intravenous (IV) infusion over 60 minutes.

End point type

Secondary

End point timeframe

Cycle 1, Day 1 (C1D1): 0.25, 2,4,10 hours(h) post dose, C1D8: 0.25h post dose, Cycle 2, Day 1 (C2D1): 0.25, 2,4,10h post dose; C3,5,7 D1: 0.25h post dose

End point values	Necitumumab
Number of subjects analysed	61 ^[14]
Units: μg/mL
geometric mean (geometric coefficient of variation)
Cycle 1, Day 1	228 ( 45.6 )
Cycle 1, Day 8 (D8)	304 ( 21.9 )
Cycle 2, Day 1	270 ( 25.6 )
Cycle 3, Day 1	318 ( 43.7 )
Cycle 5, Day 1	356 ( 42.7 )
Cycle 7, Day 1	350 ( 24.7 )

Notes
[14] - Geometric coefficient of variation is presented as a percent.

No statistical analyses for this end point

Secondary: Pharmacokinetics (PK): Maximum Concentration (Cmax) of Abemaciclib

Top of page

End point title

Pharmacokinetics (PK): Maximum Concentration (Cmax) of Abemaciclib

End point description

Pharmacokinetics (PK): Maximum Concentration (Cmax) of Abemaciclib summary of LSN3106729 noncompartmental PK parameters after twice daily oral dose of Abemaciclib.

End point type

Secondary

End point timeframe

Cycle 1, Day 1 (C1D1): 0.25, 2,4,6,8,10 hours(h) post dose, C1D8: 0.25h post dose, C2D1: 0.25, 2,4,6,8,10h post dose; C3,5,7 D1: 0.25h post dose

End point values	Abemaciclib 100 mg	Abemaciclib 150 mg	Abemaciclib 200 mg
Number of subjects analysed	3 ^[15]	5 ^[16]	5 ^[17]
Units: nanogram/milliliter (ng/mL)
geometric mean (geometric coefficient of variation)	15.6 ( 146 )	26 ( 148 )	38.2 ( 80 )

Notes
[15] - Geometric coefficient of variation is presented as a percent.
[16] - Geometric coefficient of variation is presented as a percent.
[17] - Geometric coefficient of variation is presented as a percent.

No statistical analyses for this end point

Secondary: Pharmacokinetics (PK): Area Under the Concentration Time Curve (AUC) From Zero to the Last Time Point (AUC[0-tlast]) Abemaciclib

Top of page

End point title

Pharmacokinetics (PK): Area Under the Concentration Time Curve (AUC) From Zero to the Last Time Point (AUC[0-tlast]) Abemaciclib

End point description

Pharmacokinetics (PK): Area Under the Concentration Time Curve (AUC) From Zero to the Last Time Point (AUC[0-tlast]) summary of LSN3106729 noncompartmental PK parameters after twice daily oral dose of Abemaciclib. (tlast = 10 hours)

End point type

Secondary

End point timeframe

Cycle 1, Day 1 (C1D1): 0.25, 2,4,6,8,10 hours(h) post dose

End point values	Abemaciclib 100 mg	Abemaciclib 150 mg	Abemaciclib 200 mg
Number of subjects analysed	3 ^[18]	5 ^[19]	5 ^[20]
Units: hournanogram/milliliter (hrng/mL)
geometric mean (geometric coefficient of variation)	118 ( 200 )	209 ( 136 )	336 ( 83 )

Notes
[18] - Geometric coefficient of variation is presented as a percent.
[19] - Geometric coefficient of variation is presented as a percent.
[20] - Geometric coefficient of variation is presented as a percent.

No statistical analyses for this end point

Secondary: Percentage of Participants With a Best Overall Response of Complete Response (CR), Partial Response (PR), and Stable Disease (SD) (Disease Control Rate [DCR])

Top of page

End point title

Percentage of Participants With a Best Overall Response of Complete Response (CR), Partial Response (PR), and Stable Disease (SD) (Disease Control Rate [DCR])

End point description

Disease Control Rate (DCR) is defined as the percentage of participants achieving a best overall response of stable disease (SD), PR, or CR. DCR used the same denominator as defined in ORR. Among participants counted in the denominator, the numerator counted those with a confirmed best tumor response of SD, PR, or CR per RECIST v1.1. Confidence intervals are based on Clopper-Pearson method.

End point type

Secondary

End point timeframe

Baseline to measured progressive disease or start of new anti-cancer therapy (up to 21 months)

End point values	Cohort 1 (Necitumumab 800 mg + Abemaciclib 100 mg)	Cohort 2 (Necitumumab 800 mg + Abemaciclib 150 mg)	Cohort 3 (Necitumumab 800 mg + Abemaciclib 200 mg)	Total Enrolled Participants (Necitumumab + Abemaciclib)
Number of subjects analysed	3 ^[21]	57 ^[22]	6 ^[23]	66
Units: percentage of participants
number (confidence interval 95%)	100 (29.2 to 100.0)	47.4 (34.0 to 61.0)	66.7 (22.3 to 95.7)	51.5 (38.9 to 64.0)

Notes
[21] - All enrolled participants who received at least one dose of study drug and had evaluable ORR data.
[22] - All enrolled participants who received at least one dose of study drug and had evaluable ORR data.
[23] - All enrolled participants who received at least one dose of study drug and had evaluable ORR data.

No statistical analyses for this end point

Secondary: Overall Survival

Top of page

End point title

Overall Survival

End point description

Overall survival (OS) is defined as the time from the date of study enrollment to the date of death from any cause. For each participant who is not known to have died as of the data -inclusion cutoff date for a particular analysis, OS was censored for that analysis at the last known alive date.

End point type

Secondary

End point timeframe

Baseline to date of death from any cause (24 Months)

End point values	Cohort 1 (Necitumumab 800 mg + Abemaciclib 100 mg)	Cohort 2 (Necitumumab 800 mg + Abemaciclib 150 mg)	Cohort 3 (Necitumumab 800 mg + Abemaciclib 200 mg)
Number of subjects analysed	3 ^[24]	57 ^[25]	6 ^[26]
Units: Months
median (confidence interval 95%)	9999 (18.20 to 9999)	6.93 (4.96 to 12.85)	13.45 (1.31 to 18.53)

Notes
[24] - 9999 = NA due to 95% Confidence Interval (CI) had not matured yet and median was not calculable.
[25] - All enrolled participants who received at least one dose of study drug and had evaluable OS data.
[26] - All enrolled participants who received at least one dose of study drug and had evaluable OS data.

No statistical analyses for this end point

Adverse events

Top of page

Timeframe for reporting adverse events

Up to 21 Months

Adverse event reporting additional description

I4X-MC-JFCU

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

22.0

Reporting group title

Necitumumab-800mg Abemaciclib-150mg

Reporting group description

Reporting group title

Necitumumab-800mg Abemaciclib-200mg

Reporting group description

Reporting group title

Necitumumab-800mg Abemaciclib-100mg

Reporting group description

Serious adverse events	Necitumumab-800mg Abemaciclib-150mg	Necitumumab-800mg Abemaciclib-200mg	Necitumumab-800mg Abemaciclib-100mg
Total subjects affected by serious adverse events
subjects affected / exposed	25 / 57 (43.86%)	4 / 6 (66.67%)	2 / 3 (66.67%)
number of deaths (all causes)	1	0	0
number of deaths resulting from adverse events	1	0	0
Vascular disorders
phlebitis
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	1 / 57 (1.75%)	0 / 6 (0.00%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
superior vena cava syndrome
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	1 / 57 (1.75%)	0 / 6 (0.00%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
General disorders and administration site conditions
fatigue
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	2 / 57 (3.51%)	0 / 6 (0.00%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
general physical health deterioration
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	2 / 57 (3.51%)	0 / 6 (0.00%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	1 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
pyrexia
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	2 / 57 (3.51%)	1 / 6 (16.67%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	2 / 2	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
vascular stent thrombosis
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	1 / 57 (1.75%)	0 / 6 (0.00%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
dyspnoea
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	1 / 57 (1.75%)	0 / 6 (0.00%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
pneumomediastinum
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	1 / 57 (1.75%)	0 / 6 (0.00%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
pneumonitis
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	2 / 57 (3.51%)	0 / 6 (0.00%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	1 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	1 / 1	0 / 0	0 / 0
pulmonary embolism
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	1 / 57 (1.75%)	0 / 6 (0.00%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Investigations
blood creatinine increased
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	1 / 57 (1.75%)	0 / 6 (0.00%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Injury, poisoning and procedural complications
infusion related reaction
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	0 / 57 (0.00%)	0 / 6 (0.00%)	1 / 3 (33.33%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Cardiac disorders
atrial flutter
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	1 / 57 (1.75%)	0 / 6 (0.00%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Nervous system disorders
headache
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	2 / 57 (3.51%)	0 / 6 (0.00%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	1 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
loss of consciousness
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	1 / 57 (1.75%)	0 / 6 (0.00%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
somnolence
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	1 / 57 (1.75%)	0 / 6 (0.00%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Blood and lymphatic system disorders
thrombocytopenia
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	0 / 57 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Eye disorders
blindness
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	1 / 57 (1.75%)	0 / 6 (0.00%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
diarrhoea
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	2 / 57 (3.51%)	0 / 6 (0.00%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	2 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
nausea
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	1 / 57 (1.75%)	0 / 6 (0.00%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
vomiting
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	5 / 57 (8.77%)	0 / 6 (0.00%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	5 / 6	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Hepatobiliary disorders
cholecystitis
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	0 / 57 (0.00%)	0 / 6 (0.00%)	1 / 3 (33.33%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Skin and subcutaneous tissue disorders
palmar-plantar erythrodysaesthesia syndrome
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	1 / 57 (1.75%)	0 / 6 (0.00%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Renal and urinary disorders
acute kidney injury
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	1 / 57 (1.75%)	0 / 6 (0.00%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
hydronephrosis
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	0 / 57 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
renal failure
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	1 / 57 (1.75%)	0 / 6 (0.00%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
ureterolithiasis
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	0 / 57 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Infections and infestations
anal abscess
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	0 / 57 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
device related infection
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	1 / 57 (1.75%)	0 / 6 (0.00%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
erysipelas
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	1 / 57 (1.75%)	0 / 6 (0.00%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
lung infection
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	2 / 57 (3.51%)	0 / 6 (0.00%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
pneumonia
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	1 / 57 (1.75%)	0 / 6 (0.00%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
respiratory tract infection
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	0 / 57 (0.00%)	0 / 6 (0.00%)	1 / 3 (33.33%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
urinary tract infection
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	1 / 57 (1.75%)	0 / 6 (0.00%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Metabolism and nutrition disorders
decreased appetite
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	1 / 57 (1.75%)	0 / 6 (0.00%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
hypokalaemia
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	1 / 57 (1.75%)	0 / 6 (0.00%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	Necitumumab-800mg Abemaciclib-150mg	Necitumumab-800mg Abemaciclib-200mg	Necitumumab-800mg Abemaciclib-100mg
Total subjects affected by non serious adverse events
subjects affected / exposed	57 / 57 (100.00%)	6 / 6 (100.00%)	3 / 3 (100.00%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
pyogenic granuloma
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	0 / 57 (0.00%)	0 / 6 (0.00%)	1 / 3 (33.33%)
occurrences all number	0	0	1
tumour pain
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	5 / 57 (8.77%)	0 / 6 (0.00%)	1 / 3 (33.33%)
occurrences all number	5	0	1
Vascular disorders
hypotension
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	1 / 57 (1.75%)	0 / 6 (0.00%)	1 / 3 (33.33%)
occurrences all number	1	0	1
intermittent claudication
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	0 / 57 (0.00%)	0 / 6 (0.00%)	1 / 3 (33.33%)
occurrences all number	0	0	1
General disorders and administration site conditions
asthenia
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	8 / 57 (14.04%)	1 / 6 (16.67%)	1 / 3 (33.33%)
occurrences all number	12	1	1
fatigue
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	29 / 57 (50.88%)	3 / 6 (50.00%)	2 / 3 (66.67%)
occurrences all number	49	4	6
general physical health deterioration
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	4 / 57 (7.02%)	0 / 6 (0.00%)	0 / 3 (0.00%)
occurrences all number	4	0	0
mucosal dryness
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	0 / 57 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)
occurrences all number	0	1	0
oedema peripheral
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	3 / 57 (5.26%)	1 / 6 (16.67%)	1 / 3 (33.33%)
occurrences all number	3	1	1
pain
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	5 / 57 (8.77%)	0 / 6 (0.00%)	0 / 3 (0.00%)
occurrences all number	5	0	0
pyrexia
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	10 / 57 (17.54%)	2 / 6 (33.33%)	2 / 3 (66.67%)
occurrences all number	10	2	3
xerosis
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	4 / 57 (7.02%)	0 / 6 (0.00%)	1 / 3 (33.33%)
occurrences all number	4	0	1
Reproductive system and breast disorders
vaginal discharge
alternative dictionary used: MedDRA 22.0
subjects affected / exposed ^[1]	1 / 17 (5.88%)	0 / 1 (0.00%)	0 / 1 (0.00%)
occurrences all number	1	0	0
Respiratory, thoracic and mediastinal disorders
cough
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	10 / 57 (17.54%)	1 / 6 (16.67%)	0 / 3 (0.00%)
occurrences all number	10	1	0
dysphonia
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	0 / 57 (0.00%)	0 / 6 (0.00%)	1 / 3 (33.33%)
occurrences all number	0	0	1
dyspnoea
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	21 / 57 (36.84%)	1 / 6 (16.67%)	1 / 3 (33.33%)
occurrences all number	21	3	1
epistaxis
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	0 / 57 (0.00%)	2 / 6 (33.33%)	1 / 3 (33.33%)
occurrences all number	0	2	2
haemoptysis
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	3 / 57 (5.26%)	0 / 6 (0.00%)	0 / 3 (0.00%)
occurrences all number	3	0	0
laryngeal inflammation
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	0 / 57 (0.00%)	0 / 6 (0.00%)	1 / 3 (33.33%)
occurrences all number	0	0	1
pleural effusion
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	0 / 57 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)
occurrences all number	0	1	0
Psychiatric disorders
anxiety
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	0 / 57 (0.00%)	1 / 6 (16.67%)	1 / 3 (33.33%)
occurrences all number	0	1	1
depression
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	0 / 57 (0.00%)	0 / 6 (0.00%)	1 / 3 (33.33%)
occurrences all number	0	0	1
insomnia
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	5 / 57 (8.77%)	0 / 6 (0.00%)	0 / 3 (0.00%)
occurrences all number	5	0	0
Investigations
alanine aminotransferase increased
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	5 / 57 (8.77%)	0 / 6 (0.00%)	0 / 3 (0.00%)
occurrences all number	6	0	0
aspartate aminotransferase increased
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	3 / 57 (5.26%)	0 / 6 (0.00%)	0 / 3 (0.00%)
occurrences all number	4	0	0
blood creatinine increased
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	13 / 57 (22.81%)	1 / 6 (16.67%)	0 / 3 (0.00%)
occurrences all number	23	1	0
neutrophil count decreased
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	9 / 57 (15.79%)	0 / 6 (0.00%)	0 / 3 (0.00%)
occurrences all number	18	0	0
platelet count decreased
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	11 / 57 (19.30%)	1 / 6 (16.67%)	0 / 3 (0.00%)
occurrences all number	28	1	0
weight decreased
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	7 / 57 (12.28%)	1 / 6 (16.67%)	0 / 3 (0.00%)
occurrences all number	9	2	0
Injury, poisoning and procedural complications
contusion
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	0 / 57 (0.00%)	0 / 6 (0.00%)	1 / 3 (33.33%)
occurrences all number	0	0	2
Cardiac disorders
arrhythmia
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	0 / 57 (0.00%)	0 / 6 (0.00%)	1 / 3 (33.33%)
occurrences all number	0	0	1
sinus tachycardia
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	2 / 57 (3.51%)	0 / 6 (0.00%)	1 / 3 (33.33%)
occurrences all number	2	0	1
Nervous system disorders
disturbance in attention
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	0 / 57 (0.00%)	0 / 6 (0.00%)	1 / 3 (33.33%)
occurrences all number	0	0	1
dysgeusia
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	0 / 57 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)
occurrences all number	0	1	0
headache
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	6 / 57 (10.53%)	3 / 6 (50.00%)	1 / 3 (33.33%)
occurrences all number	6	3	1
paraesthesia
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	1 / 57 (1.75%)	1 / 6 (16.67%)	1 / 3 (33.33%)
occurrences all number	1	1	1
peripheral sensory neuropathy
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	1 / 57 (1.75%)	1 / 6 (16.67%)	0 / 3 (0.00%)
occurrences all number	1	1	0
Blood and lymphatic system disorders
anaemia
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	21 / 57 (36.84%)	3 / 6 (50.00%)	1 / 3 (33.33%)
occurrences all number	45	4	1
leukocytosis
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	0 / 57 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)
occurrences all number	0	1	0
leukopenia
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	1 / 57 (1.75%)	1 / 6 (16.67%)	0 / 3 (0.00%)
occurrences all number	1	1	0
lymphopenia
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	3 / 57 (5.26%)	1 / 6 (16.67%)	0 / 3 (0.00%)
occurrences all number	3	1	0
thrombocytopenia
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	5 / 57 (8.77%)	2 / 6 (33.33%)	0 / 3 (0.00%)
occurrences all number	9	2	0
Eye disorders
cataract
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	0 / 57 (0.00%)	0 / 6 (0.00%)	1 / 3 (33.33%)
occurrences all number	0	0	1
dry eye
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	0 / 57 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)
occurrences all number	0	1	0
lacrimation increased
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	2 / 57 (3.51%)	0 / 6 (0.00%)	1 / 3 (33.33%)
occurrences all number	3	0	1
Gastrointestinal disorders
abdominal pain
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	7 / 57 (12.28%)	0 / 6 (0.00%)	0 / 3 (0.00%)
occurrences all number	7	0	0
abdominal pain upper
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	3 / 57 (5.26%)	1 / 6 (16.67%)	0 / 3 (0.00%)
occurrences all number	3	1	0
ascites
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	0 / 57 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)
occurrences all number	0	1	0
constipation
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	8 / 57 (14.04%)	0 / 6 (0.00%)	1 / 3 (33.33%)
occurrences all number	8	0	1
dental caries
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	0 / 57 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)
occurrences all number	0	1	0
diarrhoea
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	29 / 57 (50.88%)	3 / 6 (50.00%)	1 / 3 (33.33%)
occurrences all number	49	6	1
dry mouth
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	2 / 57 (3.51%)	1 / 6 (16.67%)	0 / 3 (0.00%)
occurrences all number	2	1	0
dysphagia
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	4 / 57 (7.02%)	0 / 6 (0.00%)	0 / 3 (0.00%)
occurrences all number	4	0	0
haemorrhoidal haemorrhage
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	0 / 57 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)
occurrences all number	0	1	0
nausea
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	24 / 57 (42.11%)	3 / 6 (50.00%)	0 / 3 (0.00%)
occurrences all number	32	3	0
stomatitis
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	7 / 57 (12.28%)	3 / 6 (50.00%)	0 / 3 (0.00%)
occurrences all number	8	5	0
tooth discolouration
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	0 / 57 (0.00%)	0 / 6 (0.00%)	1 / 3 (33.33%)
occurrences all number	0	0	1
vomiting
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	16 / 57 (28.07%)	3 / 6 (50.00%)	1 / 3 (33.33%)
occurrences all number	24	4	1
Hepatobiliary disorders
cholestasis
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	2 / 57 (3.51%)	1 / 6 (16.67%)	0 / 3 (0.00%)
occurrences all number	2	1	0
Skin and subcutaneous tissue disorders
dermatitis acneiform
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	26 / 57 (45.61%)	3 / 6 (50.00%)	2 / 3 (66.67%)
occurrences all number	41	5	6
dry skin
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	15 / 57 (26.32%)	4 / 6 (66.67%)	2 / 3 (66.67%)
occurrences all number	20	4	3
nail ridging
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	1 / 57 (1.75%)	1 / 6 (16.67%)	0 / 3 (0.00%)
occurrences all number	1	1	0
palmar-plantar erythrodysaesthesia syndrome
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	3 / 57 (5.26%)	0 / 6 (0.00%)	0 / 3 (0.00%)
occurrences all number	9	0	0
petechiae
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	0 / 57 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)
occurrences all number	0	1	0
pruritus
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	5 / 57 (8.77%)	0 / 6 (0.00%)	1 / 3 (33.33%)
occurrences all number	7	0	1
rash
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	8 / 57 (14.04%)	1 / 6 (16.67%)	0 / 3 (0.00%)
occurrences all number	23	1	0
rash maculo-papular
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	4 / 57 (7.02%)	0 / 6 (0.00%)	0 / 3 (0.00%)
occurrences all number	4	0	0
skin fissures
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	1 / 57 (1.75%)	0 / 6 (0.00%)	1 / 3 (33.33%)
occurrences all number	1	0	2
skin ulcer
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	1 / 57 (1.75%)	0 / 6 (0.00%)	1 / 3 (33.33%)
occurrences all number	1	0	1
Renal and urinary disorders
dysuria
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	0 / 57 (0.00%)	0 / 6 (0.00%)	1 / 3 (33.33%)
occurrences all number	0	0	1
ureterolithiasis
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	0 / 57 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)
occurrences all number	0	1	0
Musculoskeletal and connective tissue disorders
arthritis
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	1 / 57 (1.75%)	0 / 6 (0.00%)	1 / 3 (33.33%)
occurrences all number	1	0	1
back pain
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	0 / 57 (0.00%)	0 / 6 (0.00%)	1 / 3 (33.33%)
occurrences all number	0	0	1
bursitis
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	0 / 57 (0.00%)	0 / 6 (0.00%)	1 / 3 (33.33%)
occurrences all number	0	0	1
musculoskeletal pain
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	0 / 57 (0.00%)	0 / 6 (0.00%)	1 / 3 (33.33%)
occurrences all number	0	0	1
neck pain
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	0 / 57 (0.00%)	0 / 6 (0.00%)	1 / 3 (33.33%)
occurrences all number	0	0	1
osteoporosis
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	0 / 57 (0.00%)	0 / 6 (0.00%)	1 / 3 (33.33%)
occurrences all number	0	0	1
pain in extremity
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	1 / 57 (1.75%)	1 / 6 (16.67%)	1 / 3 (33.33%)
occurrences all number	1	1	1
Infections and infestations
anal abscess
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	0 / 57 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)
occurrences all number	0	1	0
bronchitis
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	4 / 57 (7.02%)	0 / 6 (0.00%)	0 / 3 (0.00%)
occurrences all number	5	0	0
conjunctivitis
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	5 / 57 (8.77%)	1 / 6 (16.67%)	1 / 3 (33.33%)
occurrences all number	5	1	1
folliculitis
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	5 / 57 (8.77%)	1 / 6 (16.67%)	0 / 3 (0.00%)
occurrences all number	8	1	0
fungal skin infection
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	0 / 57 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)
occurrences all number	0	1	0
nail infection
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	0 / 57 (0.00%)	0 / 6 (0.00%)	1 / 3 (33.33%)
occurrences all number	0	0	3
paronychia
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	6 / 57 (10.53%)	3 / 6 (50.00%)	2 / 3 (66.67%)
occurrences all number	9	3	3
pharyngitis
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	0 / 57 (0.00%)	0 / 6 (0.00%)	1 / 3 (33.33%)
occurrences all number	0	0	1
tinea pedis
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	0 / 57 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)
occurrences all number	0	1	0
upper respiratory tract infection
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	2 / 57 (3.51%)	0 / 6 (0.00%)	1 / 3 (33.33%)
occurrences all number	2	0	1
urinary tract infection
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	3 / 57 (5.26%)	0 / 6 (0.00%)	0 / 3 (0.00%)
occurrences all number	3	0	0
Metabolism and nutrition disorders
decreased appetite
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	21 / 57 (36.84%)	4 / 6 (66.67%)	2 / 3 (66.67%)
occurrences all number	24	7	3
hyperglycaemia
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	1 / 57 (1.75%)	1 / 6 (16.67%)	1 / 3 (33.33%)
occurrences all number	1	1	1
hyperkalaemia
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	3 / 57 (5.26%)	0 / 6 (0.00%)	0 / 3 (0.00%)
occurrences all number	3	0	0
hypoalbuminaemia
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	4 / 57 (7.02%)	2 / 6 (33.33%)	0 / 3 (0.00%)
occurrences all number	4	2	0
hypocalcaemia
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	1 / 57 (1.75%)	1 / 6 (16.67%)	0 / 3 (0.00%)
occurrences all number	1	1	0
hypochloraemia
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	0 / 57 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)
occurrences all number	0	1	0
hypokalaemia
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	12 / 57 (21.05%)	4 / 6 (66.67%)	1 / 3 (33.33%)
occurrences all number	17	5	2
hypomagnesaemia
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	20 / 57 (35.09%)	1 / 6 (16.67%)	0 / 3 (0.00%)
occurrences all number	29	3	0
hyponatraemia
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	4 / 57 (7.02%)	2 / 6 (33.33%)	0 / 3 (0.00%)
occurrences all number	7	2	0
hypophosphataemia
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	8 / 57 (14.04%)	1 / 6 (16.67%)	0 / 3 (0.00%)
occurrences all number	18	2	0

Notes
[1] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: This event is gender specific, only occurring in male or female subjects. The number of subjects exposed has been adjusted accordingly.

More information

Top of page

Were there any global substantial amendments to the protocol? Yes

12 May 2016

Protocol amendment (b) overall changes are as follows: • Interim efficacy analyses (as needed) have been added to aid in the planning of future trials. • Specific adverse events of necitumumab have been amended. • The infusion time for necitumumab has been updated to 60 minutes.

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

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

Clinical trials

Clinical Trial Results:
A Single-Arm, Multicenter, Phase 1b Study with an Expansion Cohort to Evaluate Safety and Efficacy of Necitumumab in Combination with Abemaciclib in Treatment of Patients with Stage IV Non-Small Cell Lung Cancer (NSCLC)

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Part A: Number of Participants with Abemaciclib Dose Limiting Toxicities (DLTs)

Primary: Part A: Number of Participants with Abemaciclib Dose Limiting Toxicities (DLTs)

Primary: Progression Free Survival (PFS) Rate at 3 Months (Percentage of Participants with PFS at 3 Months)

Primary: Progression Free Survival (PFS) Rate at 3 Months (Percentage of Participants with PFS at 3 Months)

Secondary: Percentage of Participants Who Achieve Best Overall Tumor Response of Complete or Partial Response (Objective Response Rate [ORR])

Secondary: Percentage of Participants Who Achieve Best Overall Tumor Response of Complete or Partial Response (Objective Response Rate [ORR])

Secondary: Pharmacokinetics (PK): Predose Concentration (Cmin) of Necitumumab

Secondary: Pharmacokinetics (PK): Predose Concentration (Cmin) of Necitumumab

Secondary: Pharmacokinetics (PK): Maximum Concentration (Cmax) of Necitumumab

Secondary: Pharmacokinetics (PK): Maximum Concentration (Cmax) of Necitumumab

Secondary: Pharmacokinetics (PK): Maximum Concentration (Cmax) of Abemaciclib

Secondary: Pharmacokinetics (PK): Maximum Concentration (Cmax) of Abemaciclib

Secondary: Pharmacokinetics (PK): Area Under the Concentration Time Curve (AUC) From Zero to the Last Time Point (AUC[0-tlast]) Abemaciclib

Secondary: Pharmacokinetics (PK): Area Under the Concentration Time Curve (AUC) From Zero to the Last Time Point (AUC[0-tlast]) Abemaciclib

Secondary: Percentage of Participants With a Best Overall Response of Complete Response (CR), Partial Response (PR), and Stable Disease (SD) (Disease Control Rate [DCR])

Secondary: Percentage of Participants With a Best Overall Response of Complete Response (CR), Partial Response (PR), and Stable Disease (SD) (Disease Control Rate [DCR])

Secondary: Overall Survival

Secondary: Overall Survival

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

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 Single-Arm, Multicenter, Phase 1b Study with an Expansion Cohort to Evaluate Safety and Efficacy of Necitumumab in Combination with Abemaciclib in Treatment of Patients with Stage IV Non-Small Cell Lung Cancer (NSCLC)

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Part A: Number of Participants with Abemaciclib Dose Limiting Toxicities (DLTs)

Primary: Part A: Number of Participants with Abemaciclib Dose Limiting Toxicities (DLTs)

Primary: Progression Free Survival (PFS) Rate at 3 Months (Percentage of Participants with PFS at 3 Months)

Primary: Progression Free Survival (PFS) Rate at 3 Months (Percentage of Participants with PFS at 3 Months)

Secondary: Percentage of Participants Who Achieve Best Overall Tumor Response of Complete or Partial Response (Objective Response Rate [ORR])

Secondary: Percentage of Participants Who Achieve Best Overall Tumor Response of Complete or Partial Response (Objective Response Rate [ORR])

Secondary: Pharmacokinetics (PK): Predose Concentration (Cmin) of Necitumumab

Secondary: Pharmacokinetics (PK): Predose Concentration (Cmin) of Necitumumab

Secondary: Pharmacokinetics (PK): Maximum Concentration (Cmax) of Necitumumab

Secondary: Pharmacokinetics (PK): Maximum Concentration (Cmax) of Necitumumab

Secondary: Pharmacokinetics (PK): Maximum Concentration (Cmax) of Abemaciclib

Secondary: Pharmacokinetics (PK): Maximum Concentration (Cmax) of Abemaciclib

Secondary: Pharmacokinetics (PK): Area Under the Concentration Time Curve (AUC) From Zero to the Last Time Point (AUC[0-tlast]) Abemaciclib

Secondary: Pharmacokinetics (PK): Area Under the Concentration Time Curve (AUC) From Zero to the Last Time Point (AUC[0-tlast]) Abemaciclib

Secondary: Percentage of Participants With a Best Overall Response of Complete Response (CR), Partial Response (PR), and Stable Disease (SD) (Disease Control Rate [DCR])

Secondary: Percentage of Participants With a Best Overall Response of Complete Response (CR), Partial Response (PR), and Stable Disease (SD) (Disease Control Rate [DCR])

Secondary: Overall Survival

Secondary: Overall Survival

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
A Single-Arm, Multicenter, Phase 1b Study with an Expansion Cohort to Evaluate Safety and Efficacy of Necitumumab in Combination with Abemaciclib in Treatment of Patients with Stage IV Non-Small Cell Lung Cancer (NSCLC)