Trial Outcomes & Findings for A Study of Necitumumab and Abemaciclib in Participants With Non-Small Cell Lung Cancer (NSCLC) (NCT NCT02411591)

Last Updated: 2020-07-09

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

66 participants

Primary outcome timeframe

Baseline through Cycle 1 (Up to 21 Days)

Results posted on

2020-07-09

Participant Flow

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.

Participant milestones

Participant milestones
Measure	Cohort 1 (Necitumumab 800 mg + Abemaciclib 100 mg) Part A: Necitumumab 800 milligram (mg) was administered intravenously (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.	Cohort 2 (Necitumumab 800 mg + Abemaciclib 150 mg) Part A: 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. 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.	Cohort 3 (Necitumumab 800 mg + Abemaciclib 200 mg) 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.
Overall Study STARTED	3	57	6
Overall Study Part A	3	6	6
Overall Study Expansion Cohort Part B	0	51	0
Overall Study Progressive Disease	3	42	3
Overall Study Death	0	2	0
Overall Study COMPLETED	3	47	3
Overall Study NOT COMPLETED	0	10	3

Reasons for withdrawal

Reasons for withdrawal
Measure	Cohort 2 (Necitumumab 800 mg + Abemaciclib 150 mg) Part A: 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. 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.	Cohort 3 (Necitumumab 800 mg + Abemaciclib 200 mg) 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.
Overall Study Adverse Event	4	2
Overall Study Withdrawal by Subject	3	0
Overall Study Physician Decision	3	1

Baseline Characteristics

A Study of Necitumumab and Abemaciclib in Participants With Non-Small Cell Lung Cancer (NSCLC)

Baseline characteristics by cohort

PRIMARY outcome

Timeframe: Baseline through Cycle 1 (Up to 21 Days)

Population: All participants who received at least one dose of study drug and had evaluable DLTs.

Outcome measures

Outcome measures
Measure	Cohort 1 (Necitumumab 800 mg + Abemaciclib 100 mg) n=3 Participants 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.	Cohort 2 (Necitumumab 800 mg + Abemaciclib 150 mg) n=6 Participants 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.) Treatment may continue until discontinuation criterion is met.	Cohort 3 (Necitumamab 800 mg + Abemaciclib 200 mg) n=6 Participants 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.	Total Enrolled Participants (Necitumumab + Abemaciclib) 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.
Part A: Number of Participants With Abemaciclib Dose Limiting Toxicities (DLTs)	0 Participants	1 Participants	3 Participants	—

PRIMARY outcome

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

Population: All enrolled participants who received at least one dose of study drug and had evaluable PFS data. Cohort 2 number of censored participants is 10. Cohort 2 includes total number of participants in Part A and evaluable participants of Part B.

PFS is defined as the time from baseline until first observation of 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.

Outcome measures

Outcome measures
Measure	Cohort 1 (Necitumumab 800 mg + Abemaciclib 100 mg) n=3 Participants 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.	Cohort 2 (Necitumumab 800 mg + Abemaciclib 150 mg) n=57 Participants 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.) Treatment may continue until discontinuation criterion is met.	Cohort 3 (Necitumamab 800 mg + Abemaciclib 200 mg) n=6 Participants 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.	Total Enrolled Participants (Necitumumab + Abemaciclib) 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.
Progression Free Survival (PFS) Rate at 3 Months (Percentage of Participants With PFS at 3 Months)	66.7 percentage of participants Interval 5.4 to 94.5	32.3 percentage of participants Interval 20.4 to 44.8	50.0 percentage of participants Interval 11.1 to 80.4	—

SECONDARY outcome

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

Population: All enrolled participants who received at least one dose of study drug and had evaluable ORR data in cohorts 1, 2 and 3. Cohort 2 includes total number of participants in Part A and evaluable participants of Part B.

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.

Outcome measures

Outcome measures
Measure	Cohort 1 (Necitumumab 800 mg + Abemaciclib 100 mg) n=3 Participants 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.	Cohort 2 (Necitumumab 800 mg + Abemaciclib 150 mg) n=57 Participants 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.) Treatment may continue until discontinuation criterion is met.	Cohort 3 (Necitumamab 800 mg + Abemaciclib 200 mg) n=6 Participants 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.	Total Enrolled Participants (Necitumumab + Abemaciclib) n=66 Participants 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.
Percentage of Participants Who Achieve Best Overall Tumor Response of Complete or Partial Response (Objective Response Rate [ORR]) Overall Response Rate	66.7 percentage of participants Interval 9.4 to 99.2	5.3 percentage of participants Interval 1.1 to 14.6	0.0 percentage of participants Interval 0.0 to 45.9	7.6 percentage of participants Interval 2.5 to 16.8
Percentage of Participants Who Achieve Best Overall Tumor Response of Complete or Partial Response (Objective Response Rate [ORR]) PR	66.7 percentage of participants Interval 9.4 to 99.2	5.3 percentage of participants Interval 1.1 to 14.6	0.0 percentage of participants Interval 0.0 to 45.9	7.6 percentage of participants Interval 2.5 to 16.8
Percentage of Participants Who Achieve Best Overall Tumor Response of Complete or Partial Response (Objective Response Rate [ORR]) SD	33.3 percentage of participants Interval 0.8 to 90.6	42.1 percentage of participants Interval 29.1 to 55.9	66.7 percentage of participants Interval 22.3 to 95.7	43.9 percentage of participants Interval 31.7 to 56.7
Percentage of Participants Who Achieve Best Overall Tumor Response of Complete or Partial Response (Objective Response Rate [ORR]) PD	0.0 percentage of participants Interval 0.0 to 70.8	47.4 percentage of participants Interval 34.0 to 61.0	16.7 percentage of participants Interval 0.4 to 64.1	42.4 percentage of participants Interval 30.3 to 55.2

SECONDARY outcome

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

Population: All participants who received same dose of necitumumab, pre-specified to assess as single group and had evaluable PK data.

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.

Outcome measures

Outcome measures
Measure	Cohort 1 (Necitumumab 800 mg + Abemaciclib 100 mg) n=61 Participants 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.	Cohort 2 (Necitumumab 800 mg + Abemaciclib 150 mg) 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.) Treatment may continue until discontinuation criterion is met.	Cohort 3 (Necitumamab 800 mg + Abemaciclib 200 mg) 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.	Total Enrolled Participants (Necitumumab + Abemaciclib) 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.
Pharmacokinetics (PK): Predose Concentration (Cmin) of Necitumumab Cycle 1, Day 8	64.1 microgram/milliliter (μg/mL) Standard Deviation 43.1	—	—	—
Pharmacokinetics (PK): Predose Concentration (Cmin) of Necitumumab Cycle 2, Day 1	49.6 microgram/milliliter (μg/mL) Standard Deviation 63.8	—	—	—
Pharmacokinetics (PK): Predose Concentration (Cmin) of Necitumumab Cycle 3, Day 1	93.8 microgram/milliliter (μg/mL) Standard Deviation 44.1	—	—	—
Pharmacokinetics (PK): Predose Concentration (Cmin) of Necitumumab Cycle 5, Day 1	160 microgram/milliliter (μg/mL) Standard Deviation 50.3	—	—	—
Pharmacokinetics (PK): Predose Concentration (Cmin) of Necitumumab Cycle 7, Day 1	165 microgram/milliliter (μg/mL) Standard Deviation 42.1	—	—	—

SECONDARY outcome

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

Population: All participants who received same dose of necitumumab, pre-specified to assess as single group and had evaluable PK data.

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.

Outcome measures

Outcome measures
Measure	Cohort 1 (Necitumumab 800 mg + Abemaciclib 100 mg) n=61 Participants 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.	Cohort 2 (Necitumumab 800 mg + Abemaciclib 150 mg) 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.) Treatment may continue until discontinuation criterion is met.	Cohort 3 (Necitumamab 800 mg + Abemaciclib 200 mg) 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.	Total Enrolled Participants (Necitumumab + Abemaciclib) 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.
Pharmacokinetics (PK): Maximum Concentration (Cmax) of Necitumumab Cycle 1, Day 1	228 μg/mL Geometric Coefficient of Variation 45.6	—	—	—
Pharmacokinetics (PK): Maximum Concentration (Cmax) of Necitumumab Cycle 1, Day 8 (D8)	304 μg/mL Geometric Coefficient of Variation 21.9	—	—	—
Pharmacokinetics (PK): Maximum Concentration (Cmax) of Necitumumab Cycle 2, Day 1	270 μg/mL Geometric Coefficient of Variation 25.6	—	—	—
Pharmacokinetics (PK): Maximum Concentration (Cmax) of Necitumumab Cycle 3, Day 1	318 μg/mL Geometric Coefficient of Variation 43.7	—	—	—
Pharmacokinetics (PK): Maximum Concentration (Cmax) of Necitumumab Cycle 5, Day 1	356 μg/mL Geometric Coefficient of Variation 42.7	—	—	—
Pharmacokinetics (PK): Maximum Concentration (Cmax) of Necitumumab Cycle 7, Day 1	350 μg/mL Geometric Coefficient of Variation 24.7	—	—	—

SECONDARY outcome

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

Population: All participants who received at least one dose of abemaciclib and had evaluable PK data for Part A.

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

Outcome measures

Outcome measures
Measure	Cohort 1 (Necitumumab 800 mg + Abemaciclib 100 mg) n=3 Participants 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.	Cohort 2 (Necitumumab 800 mg + Abemaciclib 150 mg) n=5 Participants 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.) Treatment may continue until discontinuation criterion is met.	Cohort 3 (Necitumamab 800 mg + Abemaciclib 200 mg) n=5 Participants 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.	Total Enrolled Participants (Necitumumab + Abemaciclib) 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.
Pharmacokinetics (PK): Maximum Concentration (Cmax) of Abemaciclib	15.6 nanogram/milliliter (ng/mL) Geometric Coefficient of Variation 146	26 nanogram/milliliter (ng/mL) Geometric Coefficient of Variation 148	38.2 nanogram/milliliter (ng/mL) Geometric Coefficient of Variation 80	—

SECONDARY outcome

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

Population: All participants who received at least one dose of abemaciclib and had evaluable PK data for Part A.

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)

Outcome measures

Outcome measures
Measure	Cohort 1 (Necitumumab 800 mg + Abemaciclib 100 mg) n=3 Participants 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.	Cohort 2 (Necitumumab 800 mg + Abemaciclib 150 mg) n=5 Participants 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.) Treatment may continue until discontinuation criterion is met.	Cohort 3 (Necitumamab 800 mg + Abemaciclib 200 mg) n=5 Participants 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.	Total Enrolled Participants (Necitumumab + Abemaciclib) 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.
Pharmacokinetics (PK): Area Under the Concentration Time Curve (AUC) From Zero to the Last Time Point (AUC[0-tlast]) Abemaciclib	118 hournanogram/milliliter (hrng/mL) Geometric Coefficient of Variation 200	209 hournanogram/milliliter (hrng/mL) Geometric Coefficient of Variation 136	336 hournanogram/milliliter (hrng/mL) Geometric Coefficient of Variation 83	—

SECONDARY outcome

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

Population: All enrolled participants who received at least one dose of study drug and had evaluable ORR data in cohorts 1, 2 and 3.Cohort 2 includes total number of participants in Part A and evaluable participants of Part B.

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.

Outcome measures

Outcome measures
Measure	Cohort 1 (Necitumumab 800 mg + Abemaciclib 100 mg) n=3 Participants 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.	Cohort 2 (Necitumumab 800 mg + Abemaciclib 150 mg) n=57 Participants 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.) Treatment may continue until discontinuation criterion is met.	Cohort 3 (Necitumamab 800 mg + Abemaciclib 200 mg) n=6 Participants 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.	Total Enrolled Participants (Necitumumab + Abemaciclib) n=66 Participants 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.
Percentage of Participants With a Best Overall Response of Complete Response (CR), Partial Response (PR), and Stable Disease (SD) (Disease Control Rate [DCR])	100 percentage of participants Interval 29.2 to 100.0	47.4 percentage of participants Interval 34.0 to 61.0	66.7 percentage of participants Interval 22.3 to 95.7	51.5 percentage of participants Interval 38.9 to 64.0

SECONDARY outcome

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

Population: All enrolled participants who received at least one dose of study drug and had evaluable overall survival (OS) data. Cohort 2 includes total number of participants in Part A and evaluable participants of Part B. Participants censored in cohort 1 = 2, cohort 2 = 1 and cohort 3 = 21.

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.

Outcome measures

Outcome measures
Measure	Cohort 1 (Necitumumab 800 mg + Abemaciclib 100 mg) n=3 Participants 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.	Cohort 2 (Necitumumab 800 mg + Abemaciclib 150 mg) n=57 Participants 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.) Treatment may continue until discontinuation criterion is met.	Cohort 3 (Necitumamab 800 mg + Abemaciclib 200 mg) n=6 Participants 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.	Total Enrolled Participants (Necitumumab + Abemaciclib) 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.
Overall Survival	NA Months Interval 18.2 to 95% Confidence Interval (CI) had not matured yet and median was not calculable.	6.93 Months Interval 4.96 to 12.85	13.45 Months Interval 1.31 to 18.53	—

Adverse Events

Necitumumab 800 mg + Abemaciclib 100 mg

Serious events: 2 serious events

Other events: 3 other events

Deaths: 0 deaths

Necitumumab 800 mg + Abemaciclib 150 mg

Serious events: 25 serious events

Other events: 57 other events

Deaths: 5 deaths

Necitumumab 800 mg + Abemaciclib 200 mg

Serious events: 4 serious events

Other events: 6 other events

Deaths: 2 deaths

Serious adverse events

Other adverse events

Additional Information

Chief Medical Officer

Eli Lilly and Company

Phone: 800-545-5979

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: GT60

Measure	Cohort 1 (Necitumumab 800 mg + Abemaciclib 100 mg) n=3 Participants 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.	Cohort 2 (Necitumumab 800 mg + Abemaciclib 150 mg) n=57 Participants Part A: 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.) Treatment may continue until discontinuation criterion is met. Part B (expansion cohort) : Necitumumab administered IV on Days 1 and 8, followed by abemaciclib given orally every 12 hours on Days 1 to 21. (21 day cycles.) Treatment may continue until discontinuation criterion is met.	Cohort 3 (Necitumumab 800 mg + Abemaciclib 200 mg) n=6 Participants Part A: Necitumumab 800 mg was administered IV on Days 1 and 8, followed by abemaciclib 200 mg given orally Q12H on Days 1 to 21. (21 day cycles.) Treatment may continue until discontinuation criterion is met.	Total n=66 Participants Total of all reporting groups
Age, Continuous	62.33 years STANDARD_DEVIATION 2.31 • n=5 Participants	61.42 years STANDARD_DEVIATION 10.58 • n=7 Participants	49.00 years STANDARD_DEVIATION 7.59 • n=5 Participants	60.33 years STANDARD_DEVIATION 10.68 • n=4 Participants
Sex: Female, Male Female	1 Participants n=5 Participants	17 Participants n=7 Participants	1 Participants n=5 Participants	19 Participants n=4 Participants
Sex: Female, Male Male	2 Participants n=5 Participants	40 Participants n=7 Participants	5 Participants n=5 Participants	47 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	2 Participants n=7 Participants	0 Participants n=5 Participants	2 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	1 Participants n=5 Participants	13 Participants n=7 Participants	1 Participants n=5 Participants	15 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	2 Participants n=5 Participants	42 Participants n=7 Participants	5 Participants n=5 Participants	49 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) White	1 Participants n=5 Participants	16 Participants n=7 Participants	1 Participants n=5 Participants	18 Participants n=4 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	2 Participants n=5 Participants	41 Participants n=7 Participants	5 Participants n=5 Participants	48 Participants n=4 Participants
Region of Enrollment Belgium	1 Participants n=5 Participants	9 Participants n=7 Participants	1 Participants n=5 Participants	11 Participants n=4 Participants
Region of Enrollment France	2 Participants n=5 Participants	45 Participants n=7 Participants	5 Participants n=5 Participants	52 Participants n=4 Participants
Region of Enrollment Spain	0 Participants n=5 Participants	3 Participants n=7 Participants	0 Participants n=5 Participants	3 Participants n=4 Participants