Trial Outcomes & Findings for A Study of Necitumumab in the First-Line Treatment of Stage IV Squamous Non-Small Cell Lung Cancer (NSCLC) (NCT NCT01763788)

Last Updated: 2019-10-25

Results Overview

DLT was defined as any of the following events graded according to the National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events (CTCAE) version 4.0, when the event occurred within 21 days from Day 1 in Cycle 1 and was considered to be definitely or probably related to necitumumab and/or gemcitabine-cisplatin chemotherapy: Grade 4 neutropenia ≥ 7 days, Grade ≥ 3 febrile neutropenia except for transient febrile neutropenia (Grade 3 neutropenia with fever ≥ 38.5 degrees Celsius (°C) for ≤ 24 hours), Grade 3 thrombocytopenia requiring platelet substitution, Grade 4 thrombocytopenia, ≥Grade 3 nonhematologic toxicity (excluding nausea, vomiting, arthralgia, myalgia, asthenia, fatigue, diarrhea, constipation, anorexia), any toxicity leading to the omission of necitumumab on Day 8 or 15 (for participants for whom necitumumab was delayed from Days 8 to 15) during the Cycle 1.

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

192 participants

Primary outcome timeframe

Day 1 to Day 21 in Cycle 1 (Up To 21 days)

Results posted on

2019-10-25

Participant Flow

Completers included participants who died from any cause and participants who were alive and on study (but off treatment) at study conclusion.

Participant milestones

Participant milestones
Measure	Phase 1b: Cohort 1 Gemcitabine at a dose of 1000 mg/m\^2 (milligrams per square meter) was administered over approximately 30 minutes intravenously (IV) on Days 1 and 8 of each cycle for a maximum of 4 cycles. Cisplatin at a dose of 75 mg/m\^2 was administered over approximately 120 minutes IV on Day 1 for a maximum of 4 cycles. Necitumumab at a dose of 800 mg was administered over approximately 50 minutes intravenously IV on Days 1 and 8 of each 3-week cycle.	Phase 1b: Cohort 2 Gemcitabine at a dose of 1250 mg/m\^2 was administered over approximately 30 minutes IV on Days 1 and 8 of each cycle for a maximum of 4 cycles. Cisplatin at a dose of 75 mg/m\^2 was administered over approximately 120 minutes IV on Day 1 for a maximum of 4 cycles. Necitumumab at a dose of 800 mg was administered over approximately 50 minutes intravenously IV on Days 1 and 8 of each 3-week cycle.	Phase 2: GC+N (Gemcitabine, Cisplatin + Necitumumab) Gemcitabine at a dose of 1250 mg/m\^2 was administered over approximately 30 minutes IV on Days 1 and 8 of each cycle for a maximum of 4 cycles. Cisplatin at a dose of 75 mg/m\^2 was administered over approximately 120 minutes IV on Day 1 for a maximum of 4 cycles. Necitumumab at a dose of 800 mg was administered over approximately 50 minutes intravenously IV on Days 1 and 8 of each 3-week cycle.	Phase 2: GC (Gemcitabine, Cisplatin) Gemcitabine at a dose of 1250 mg/m\^2 was administered over approximately 30 minutes IV on Days 1 and 8 of each cycle for a maximum of 4 cycles. Cisplatin at a dose of 75 mg/m\^2 was administered over approximately 120 minutes IV on Day 1 for a maximum of 4 cycles.
Overall Study STARTED	3	6	91	92
Overall Study Received at Least 1dose of Study Drug	3	6	90	91
Overall Study COMPLETED	3	6	90	92
Overall Study NOT COMPLETED	0	0	1	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Phase 1b: Cohort 1 Gemcitabine at a dose of 1000 mg/m\^2 (milligrams per square meter) was administered over approximately 30 minutes intravenously (IV) on Days 1 and 8 of each cycle for a maximum of 4 cycles. Cisplatin at a dose of 75 mg/m\^2 was administered over approximately 120 minutes IV on Day 1 for a maximum of 4 cycles. Necitumumab at a dose of 800 mg was administered over approximately 50 minutes intravenously IV on Days 1 and 8 of each 3-week cycle.	Phase 1b: Cohort 2 Gemcitabine at a dose of 1250 mg/m\^2 was administered over approximately 30 minutes IV on Days 1 and 8 of each cycle for a maximum of 4 cycles. Cisplatin at a dose of 75 mg/m\^2 was administered over approximately 120 minutes IV on Day 1 for a maximum of 4 cycles. Necitumumab at a dose of 800 mg was administered over approximately 50 minutes intravenously IV on Days 1 and 8 of each 3-week cycle.	Phase 2: GC+N (Gemcitabine, Cisplatin + Necitumumab) Gemcitabine at a dose of 1250 mg/m\^2 was administered over approximately 30 minutes IV on Days 1 and 8 of each cycle for a maximum of 4 cycles. Cisplatin at a dose of 75 mg/m\^2 was administered over approximately 120 minutes IV on Day 1 for a maximum of 4 cycles. Necitumumab at a dose of 800 mg was administered over approximately 50 minutes intravenously IV on Days 1 and 8 of each 3-week cycle.	Phase 2: GC (Gemcitabine, Cisplatin) Gemcitabine at a dose of 1250 mg/m\^2 was administered over approximately 30 minutes IV on Days 1 and 8 of each cycle for a maximum of 4 cycles. Cisplatin at a dose of 75 mg/m\^2 was administered over approximately 120 minutes IV on Day 1 for a maximum of 4 cycles.
Overall Study Lost to Follow-up	0	0	1	0

Baseline Characteristics

A Study of Necitumumab in the First-Line Treatment of Stage IV Squamous Non-Small Cell Lung Cancer (NSCLC)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Phase 1b: Cohort 1 n=3 Participants Gemcitabine at a dose of 1000 mg/m\^2 was administered over approximately 30 minutes IV on Days 1 and 8 of each cycle for a maximum of 4 cycles. Cisplatin at a dose of 75 mg/m\^2 was administered over approximately 120 minutes IV on Day 1 for a maximum of 4 cycles. Necitumumab at a dose of 800 mg was administered over approximately 50 minutes intravenously IV on Days 1 and 8 of each 3-week cycle.	Phase 1b: Cohort 2 n=6 Participants Gemcitabine at a dose of 1250 mg/m\^2 was administered over approximately 30 minutes IV on Days 1 and 8 of each cycle for a maximum of 4 cycles. Cisplatin at a dose of 75 mg/m\^2 was administered over approximately 120 minutes IV on Day 1 for a maximum of 4 cycles. Necitumumab at a dose of 800 mg was administered over approximately 50 minutes intravenously IV on Days 1 and 8 of each 3-week cycle.	Phase 2: GC+N (Gemcitabine, Cisplatin + Necitumumab) n=90 Participants Gemcitabine at a dose of 1250 mg/m\^2 was administered over approximately 30 minutes IV on Days 1 and 8 of each cycle for a maximum of 4 cycles. Cisplatin at a dose of 75 mg/m\^2 was administered over approximately 120 minutes IV on Day 1 for a maximum of 4 cycles. Necitumumab at a dose of 800 mg was administered over approximately 50 minutes intravenously IV on Days 1 and 8 of each 3-week cycle.	Phase 2: GC (Gemcitabine, Cisplatin) n=91 Participants Gemcitabine at a dose of 1250 mg/m\^2 was administered over approximately 30 minutes IV on Days 1 and 8 of each cycle for a maximum of 4 cycles. Cisplatin at a dose of 75 mg/m\^2 was administered over approximately 120 minutes IV on Day 1 for a maximum of 4 cycles.	Total n=190 Participants Total of all reporting groups
Age, Continuous	71.0 years n=5 Participants	66.0 years n=7 Participants	66.5 years n=5 Participants	65.0 years n=4 Participants	66.0 years n=21 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	1 Participants n=7 Participants	11 Participants n=5 Participants	10 Participants n=4 Participants	22 Participants n=21 Participants
Sex: Female, Male Male	3 Participants n=5 Participants	5 Participants n=7 Participants	79 Participants n=5 Participants	81 Participants n=4 Participants	168 Participants n=21 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	0 Participants n=21 Participants
Race (NIH/OMB) Asian	3 Participants n=5 Participants	6 Participants n=7 Participants	90 Participants n=5 Participants	89 Participants n=4 Participants	188 Participants n=21 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	0 Participants n=21 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	0 Participants n=21 Participants
Race (NIH/OMB) White	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	1 Participants n=21 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	1 Participants n=21 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants

PRIMARY outcome

Timeframe: Day 1 to Day 21 in Cycle 1 (Up To 21 days)

Population: All enrolled participants who received at least one dose of study drug during study Phase 1b.

Outcome measures

Outcome measures
Measure	Phase 1b: Cohort 1 n=3 Participants Gemcitabine at a dose of 1000 mg/m\^2 was administered over approximately 30 minutes IV on Days 1 and 8 of each cycle for a maximum of 4 cycles. Cisplatin at a dose of 75 mg/m\^2 was administered over approximately 120 minutes IV on Day 1 for a maximum of 4 cycles. Necitumumab at a dose of 800 mg was administered over approximately 50 minutes intravenously IV on Days 1 and 8 of each 3-week cycle.	Phase 1b: Cohort 2 n=6 Participants Gemcitabine at a dose of 1250 mg/m\^2 was administered over approximately 30 minutes IV on Days 1 and 8 of each cycle for a maximum of 4 cycles. Cisplatin at a dose of 75 mg/m\^2 was administered over approximately 120 minutes IV on Day 1 for a maximum of 4 cycles. Necitumumab at a dose of 800 mg was administered over approximately 50 minutes intravenously IV on Days 1 and 8 of each 3-week cycle.
Phase 1b: Number of Participants With Dose Limiting Toxicities (DLTs)	0 Participants	0 Participants

PRIMARY outcome

Timeframe: From Date of Randomization until Death Due to Any Cause (Up To 39 Months)

Population: All randomized participants who received at least one dose of study drug during study Phase 2. Censored participants in the GC+N Arm = 27 and in the GC Arm = 17.

OS defined as the time from the date of randomization to the date of death due to any cause. Participants who are alive at the time of study completion or are lost to follow-up will be censored at the time they were last known to be alive.

Outcome measures

Outcome measures
Measure	Phase 1b: Cohort 1 n=90 Participants Gemcitabine at a dose of 1000 mg/m\^2 was administered over approximately 30 minutes IV on Days 1 and 8 of each cycle for a maximum of 4 cycles. Cisplatin at a dose of 75 mg/m\^2 was administered over approximately 120 minutes IV on Day 1 for a maximum of 4 cycles. Necitumumab at a dose of 800 mg was administered over approximately 50 minutes intravenously IV on Days 1 and 8 of each 3-week cycle.	Phase 1b: Cohort 2 n=91 Participants Gemcitabine at a dose of 1250 mg/m\^2 was administered over approximately 30 minutes IV on Days 1 and 8 of each cycle for a maximum of 4 cycles. Cisplatin at a dose of 75 mg/m\^2 was administered over approximately 120 minutes IV on Day 1 for a maximum of 4 cycles. Necitumumab at a dose of 800 mg was administered over approximately 50 minutes intravenously IV on Days 1 and 8 of each 3-week cycle.
Phase 2: Overall Survival (OS)	14.92 Months Interval 13.37 to 18.17	10.84 Months Interval 8.9 to 14.39

SECONDARY outcome

Timeframe: From Date of Randomization to Measured Progressive Disease or Death Due to Any Cause (Up To 39 Months)

Population: All randomized participants who received at least one dose of study during study Phase 2. Censored participants in the GC+N Arm = 6 and in the GC Arm = 10.

PFS defined as time from date of randomization 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 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	Phase 1b: Cohort 1 n=90 Participants Gemcitabine at a dose of 1000 mg/m\^2 was administered over approximately 30 minutes IV on Days 1 and 8 of each cycle for a maximum of 4 cycles. Cisplatin at a dose of 75 mg/m\^2 was administered over approximately 120 minutes IV on Day 1 for a maximum of 4 cycles. Necitumumab at a dose of 800 mg was administered over approximately 50 minutes intravenously IV on Days 1 and 8 of each 3-week cycle.	Phase 1b: Cohort 2 n=91 Participants Gemcitabine at a dose of 1250 mg/m\^2 was administered over approximately 30 minutes IV on Days 1 and 8 of each cycle for a maximum of 4 cycles. Cisplatin at a dose of 75 mg/m\^2 was administered over approximately 120 minutes IV on Day 1 for a maximum of 4 cycles. Necitumumab at a dose of 800 mg was administered over approximately 50 minutes intravenously IV on Days 1 and 8 of each 3-week cycle.
Phase 2: Progression Free Survival (PFS)	4.21 Months Interval 4.14 to 4.27	4.01 Months Interval 3.52 to 4.17

SECONDARY outcome

Timeframe: Baseline to Measured Progressive Disease (Up To 39 Months)

Population: All randomized participants who received at least one dose of study drug during study Phase 1b.

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.

Outcome measures

Outcome measures
Measure	Phase 1b: Cohort 1 n=3 Participants Gemcitabine at a dose of 1000 mg/m\^2 was administered over approximately 30 minutes IV on Days 1 and 8 of each cycle for a maximum of 4 cycles. Cisplatin at a dose of 75 mg/m\^2 was administered over approximately 120 minutes IV on Day 1 for a maximum of 4 cycles. Necitumumab at a dose of 800 mg was administered over approximately 50 minutes intravenously IV on Days 1 and 8 of each 3-week cycle.	Phase 1b: Cohort 2 n=6 Participants Gemcitabine at a dose of 1250 mg/m\^2 was administered over approximately 30 minutes IV on Days 1 and 8 of each cycle for a maximum of 4 cycles. Cisplatin at a dose of 75 mg/m\^2 was administered over approximately 120 minutes IV on Day 1 for a maximum of 4 cycles. Necitumumab at a dose of 800 mg was administered over approximately 50 minutes intravenously IV on Days 1 and 8 of each 3-week cycle.
Phase 1b: Percentage of Participants Who Achieve Best Overall Tumor Response of Complete Response or Partial Response (Objective Tumor Response Rate [ORR])	0.0 percentage of participants Interval 0.0 to 0.0	83.3 percentage of participants Interval 53.5 to 100.0

SECONDARY outcome

Timeframe: Baseline to Measured Progressive Disease (Up To 39 Months)

Population: All randomized participants who received at least one dose of study drug during study Phase 2.

Outcome measures

Outcome measures
Measure	Phase 1b: Cohort 1 n=90 Participants Gemcitabine at a dose of 1000 mg/m\^2 was administered over approximately 30 minutes IV on Days 1 and 8 of each cycle for a maximum of 4 cycles. Cisplatin at a dose of 75 mg/m\^2 was administered over approximately 120 minutes IV on Day 1 for a maximum of 4 cycles. Necitumumab at a dose of 800 mg was administered over approximately 50 minutes intravenously IV on Days 1 and 8 of each 3-week cycle.	Phase 1b: Cohort 2 n=91 Participants Gemcitabine at a dose of 1250 mg/m\^2 was administered over approximately 30 minutes IV on Days 1 and 8 of each cycle for a maximum of 4 cycles. Cisplatin at a dose of 75 mg/m\^2 was administered over approximately 120 minutes IV on Day 1 for a maximum of 4 cycles. Necitumumab at a dose of 800 mg was administered over approximately 50 minutes intravenously IV on Days 1 and 8 of each 3-week cycle.
Phase 2: Percentage of Participants Who Achieve Best Overall Tumor Response of Complete Response or Partial Response (Objective Tumor Response Rate [ORR])	51.1 percentage of participants Interval 40.8 to 61.4	20.9 percentage of participants Interval 12.5 to 29.2

SECONDARY outcome

Timeframe: From Date of Randomization to Measured Progressive Disease, Death Due to Any Cause, Discontinuation of Treatment or Initiation of New Anticancer Therapy (Up To 39 Months)

Population: All randomized participants who received at least one dose of study drug during study Phase 2. Censored participants in the GC+N Arm = 1 and in the GC Arm = 0.

TTF was time from the date of randomization until the date of the first observation of radiographically documented progressive disease (PD), death due to any cause, discontinuation of treatment for any reason, or initiation of new anticancer therapy. 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. Time to treatment failure was censored at the date of the last follow-up visit for participants who did not discontinue early, who were still alive, and who have not progressed.

Outcome measures

Outcome measures
Measure	Phase 1b: Cohort 1 n=90 Participants Gemcitabine at a dose of 1000 mg/m\^2 was administered over approximately 30 minutes IV on Days 1 and 8 of each cycle for a maximum of 4 cycles. Cisplatin at a dose of 75 mg/m\^2 was administered over approximately 120 minutes IV on Day 1 for a maximum of 4 cycles. Necitumumab at a dose of 800 mg was administered over approximately 50 minutes intravenously IV on Days 1 and 8 of each 3-week cycle.	Phase 1b: Cohort 2 n=91 Participants Gemcitabine at a dose of 1250 mg/m\^2 was administered over approximately 30 minutes IV on Days 1 and 8 of each cycle for a maximum of 4 cycles. Cisplatin at a dose of 75 mg/m\^2 was administered over approximately 120 minutes IV on Day 1 for a maximum of 4 cycles. Necitumumab at a dose of 800 mg was administered over approximately 50 minutes intravenously IV on Days 1 and 8 of each 3-week cycle.
Phase 2: Time to Treatment Failure (TTF)	4.16 Months Interval 4.01 to 4.24	3.75 Months Interval 2.92 to 4.01

SECONDARY outcome

Timeframe: Baseline, Cycle 4 (Cycle = 3 weeks)

Population: All randomized participants who received at least one dose of study drug and had evaluable baseline and post-baseline EQ-5D data during study Phase 2.

EQ-5D measures mobility, self-care, usual activities, pain/discomfort, anxiety/depression. 3 severity levels: no, some, severe problems. The index score was calculated from a set of item weights to derive a score on a theoretical scale of 0 to 1, with 1 representing the best health status and zero representing death based on item weights for the Japanese population. One Cycle = 3 weeks and it can be delayed up to 6 weeks.

Outcome measures

Outcome measures
Measure	Phase 1b: Cohort 1 n=77 Participants Gemcitabine at a dose of 1000 mg/m\^2 was administered over approximately 30 minutes IV on Days 1 and 8 of each cycle for a maximum of 4 cycles. Cisplatin at a dose of 75 mg/m\^2 was administered over approximately 120 minutes IV on Day 1 for a maximum of 4 cycles. Necitumumab at a dose of 800 mg was administered over approximately 50 minutes intravenously IV on Days 1 and 8 of each 3-week cycle.	Phase 1b: Cohort 2 n=61 Participants Gemcitabine at a dose of 1250 mg/m\^2 was administered over approximately 30 minutes IV on Days 1 and 8 of each cycle for a maximum of 4 cycles. Cisplatin at a dose of 75 mg/m\^2 was administered over approximately 120 minutes IV on Day 1 for a maximum of 4 cycles. Necitumumab at a dose of 800 mg was administered over approximately 50 minutes intravenously IV on Days 1 and 8 of each 3-week cycle.
Phase 2: Change From Baseline in EuroQol 5-Dimensional 3 Level (EuroQol-5D-3L) Index Score	0.04 Score on a scale Standard Deviation 0.16	0.03 Score on a scale Standard Deviation 0.17

SECONDARY outcome

Timeframe: Baseline, Cycle 4 (Cycle = 3 weeks)

Population: All randomized participants who received at least one dose of study drug and had had evaluable baseline and post-baseline EQ-5D data during study Phase 2.

EQ-5D VAS allowed participants to rate their present health condition. Possible scores ranged from 0 (worst imaginable health state) to 100 (best imaginable health state). One Cycle = 3 weeks and it can be delayed up to 6 weeks.

Outcome measures

Outcome measures
Measure	Phase 1b: Cohort 1 n=77 Participants Gemcitabine at a dose of 1000 mg/m\^2 was administered over approximately 30 minutes IV on Days 1 and 8 of each cycle for a maximum of 4 cycles. Cisplatin at a dose of 75 mg/m\^2 was administered over approximately 120 minutes IV on Day 1 for a maximum of 4 cycles. Necitumumab at a dose of 800 mg was administered over approximately 50 minutes intravenously IV on Days 1 and 8 of each 3-week cycle.	Phase 1b: Cohort 2 n=61 Participants Gemcitabine at a dose of 1250 mg/m\^2 was administered over approximately 30 minutes IV on Days 1 and 8 of each cycle for a maximum of 4 cycles. Cisplatin at a dose of 75 mg/m\^2 was administered over approximately 120 minutes IV on Day 1 for a maximum of 4 cycles. Necitumumab at a dose of 800 mg was administered over approximately 50 minutes intravenously IV on Days 1 and 8 of each 3-week cycle.
Phase 2: Change From Baseline in EuroQol 5-Dimensional 3 Level (EuroQol-5D-3L) Visual Analog Scale (VAS)	7.81 units on a scale Standard Deviation 18.90	11.10 units on a scale Standard Deviation 18.03

SECONDARY outcome

Timeframe: Baseline, Cycle 4 (Cycle = 3 weeks)

Population: All randomized participants who received at least one dose of study drug had evaluable baseline and post-baseline LCSS data. One Cycle = 3 weeks and it can be delayed up to 6 weeks.

The LCSS is a validated and reliable instrument to assess lung cancer-specific symptoms and their impact on QOL.The LCSS total score was defined as the mean of the 9 items of the scale and the average symptom burden index (ASBI) is defined as the mean of 6 symptom-specific lung cancer questions. Each of the 9 symptom or summary items is assessed on a 100-mm visual analogue scale (VAS), with 0 representing no symptoms or better QOL.

Outcome measures

Outcome measures
Measure	Phase 1b: Cohort 1 n=90 Participants Gemcitabine at a dose of 1000 mg/m\^2 was administered over approximately 30 minutes IV on Days 1 and 8 of each cycle for a maximum of 4 cycles. Cisplatin at a dose of 75 mg/m\^2 was administered over approximately 120 minutes IV on Day 1 for a maximum of 4 cycles. Necitumumab at a dose of 800 mg was administered over approximately 50 minutes intravenously IV on Days 1 and 8 of each 3-week cycle.	Phase 1b: Cohort 2 n=91 Participants Gemcitabine at a dose of 1250 mg/m\^2 was administered over approximately 30 minutes IV on Days 1 and 8 of each cycle for a maximum of 4 cycles. Cisplatin at a dose of 75 mg/m\^2 was administered over approximately 120 minutes IV on Day 1 for a maximum of 4 cycles. Necitumumab at a dose of 800 mg was administered over approximately 50 minutes intravenously IV on Days 1 and 8 of each 3-week cycle.
Phase 2: Change From Baseline in Lung Cancer Symptom Scale (LCSS) LCSS Total Score	-8.01 units on a scale Standard Deviation 13.64	-9.04 units on a scale Standard Deviation 16.32
Phase 2: Change From Baseline in Lung Cancer Symptom Scale (LCSS) Loss of Appetite	-4.48 units on a scale Standard Deviation 26.20	-9.03 units on a scale Standard Deviation 29.32
Phase 2: Change From Baseline in Lung Cancer Symptom Scale (LCSS) Fatigue	-5.42 units on a scale Standard Deviation 26.63	-4.02 units on a scale Standard Deviation 26.47
Phase 2: Change From Baseline in Lung Cancer Symptom Scale (LCSS) Cough	-18.00 units on a scale Standard Deviation 24.17	-15.82 units on a scale Standard Deviation 30.59
Phase 2: Change From Baseline in Lung Cancer Symptom Scale (LCSS) Dyspnea	-5.14 units on a scale Standard Deviation 22.51	-5.08 units on a scale Standard Deviation 24.51
Phase 2: Change From Baseline in Lung Cancer Symptom Scale (LCSS) Hemoptysis	-4.75 units on a scale Standard Deviation 21.75	-4.10 units on a scale Standard Deviation 16.46
Phase 2: Change From Baseline in Lung Cancer Symptom Scale (LCSS) Pain	-10.68 units on a scale Standard Deviation 22.07	-12.38 units on a scale Standard Deviation 26.99
Phase 2: Change From Baseline in Lung Cancer Symptom Scale (LCSS) Overall Symptoms	-11.62 units on a scale Standard Deviation 23.20	-9.56 units on a scale Standard Deviation 24.61
Phase 2: Change From Baseline in Lung Cancer Symptom Scale (LCSS) Interference	-6.92 units on a scale Standard Deviation 26.70	-5.93 units on a scale Standard Deviation 29.78
Phase 2: Change From Baseline in Lung Cancer Symptom Scale (LCSS) Quality of Life	-5.10 units on a scale Standard Deviation 23.83	-15.43 units on a scale Standard Deviation 28.46
Phase 2: Change From Baseline in Lung Cancer Symptom Scale (LCSS) Average Symptom Burden Index (ASBI)	-8.08 units on a scale Standard Deviation 12.81	-8.40 units on a scale Standard Deviation 16.24

SECONDARY outcome

Timeframe: Cycle 1 (C1) Day 1 (D1) and C3 D1: Predose, End-of-infusion and 1, 3, 6, 24, 96, 168 h post-end-of-infusion

Population: All enrolled participants who had adequate data to calculate at least 1 PK parameter during study Phase 1b. In cohort 1 (cycle 3), zero participants were analyzed because no data was collected for the outcome measure.

The Cmax is observed maximum serum concentration, taken directly from the serum concentration-time profile.

Outcome measures

Outcome measures
Measure	Phase 1b: Cohort 1 n=3 Participants Gemcitabine at a dose of 1000 mg/m\^2 was administered over approximately 30 minutes IV on Days 1 and 8 of each cycle for a maximum of 4 cycles. Cisplatin at a dose of 75 mg/m\^2 was administered over approximately 120 minutes IV on Day 1 for a maximum of 4 cycles. Necitumumab at a dose of 800 mg was administered over approximately 50 minutes intravenously IV on Days 1 and 8 of each 3-week cycle.	Phase 1b: Cohort 2 n=6 Participants Gemcitabine at a dose of 1250 mg/m\^2 was administered over approximately 30 minutes IV on Days 1 and 8 of each cycle for a maximum of 4 cycles. Cisplatin at a dose of 75 mg/m\^2 was administered over approximately 120 minutes IV on Day 1 for a maximum of 4 cycles. Necitumumab at a dose of 800 mg was administered over approximately 50 minutes intravenously IV on Days 1 and 8 of each 3-week cycle.
Phase 1b: Pharmacokinetics (PK): Maximum Concentration (Cmax) of Necitumumab Cycle 1	454 micrograms/milliliter (µg/ml) Geometric Coefficient of Variation 6	371 micrograms/milliliter (µg/ml) Geometric Coefficient of Variation 32
Phase 1b: Pharmacokinetics (PK): Maximum Concentration (Cmax) of Necitumumab Cycle 3	—	372 micrograms/milliliter (µg/ml) Geometric Coefficient of Variation 15

SECONDARY outcome

Timeframe: Gemcitabine: Cycle 1(C1) Day1(D1): Predose, End-of-infusion and 0.5, 1, 2 h post-end-of-infusion; Cisplatin:C1 D1: Predose, End-of-infusion and 3, 21, 93, 165 h post-end-of-infusion

Population: All enrolled participants who had adequate data to calculate at least 1 PK parameter during study Phase 1b.

The Cmax is observed maximum plasma concentration, taken directly from the plasma concentration-time profile.

Outcome measures

Outcome measures
Measure	Phase 1b: Cohort 1 n=3 Participants Gemcitabine at a dose of 1000 mg/m\^2 was administered over approximately 30 minutes IV on Days 1 and 8 of each cycle for a maximum of 4 cycles. Cisplatin at a dose of 75 mg/m\^2 was administered over approximately 120 minutes IV on Day 1 for a maximum of 4 cycles. Necitumumab at a dose of 800 mg was administered over approximately 50 minutes intravenously IV on Days 1 and 8 of each 3-week cycle.	Phase 1b: Cohort 2 n=6 Participants Gemcitabine at a dose of 1250 mg/m\^2 was administered over approximately 30 minutes IV on Days 1 and 8 of each cycle for a maximum of 4 cycles. Cisplatin at a dose of 75 mg/m\^2 was administered over approximately 120 minutes IV on Day 1 for a maximum of 4 cycles. Necitumumab at a dose of 800 mg was administered over approximately 50 minutes intravenously IV on Days 1 and 8 of each 3-week cycle.
Phase 1b: PK: Cmax of Gemcitabine and Cisplatin Gemcitabine	17400 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 8	26000 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 16
Phase 1b: PK: Cmax of Gemcitabine and Cisplatin Cisplatin	3740 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 14	3980 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 10

SECONDARY outcome

Timeframe: Cycle 1 (C1) Day 1 (D1) and C3 D1: Predose, End-of-infusion and 1, 3, 6, 24, 96, 168 h post-end-of-infusion

Population: All enrolled participants who had adequate data to calculate at least 1 PK parameter during study Phase 1b. In cohort 1 and 2 (cycle 3), zero participants were analyzed because no data was collected for the outcome measure.

The AUC(0-infinity) is area under the serum concentration-time curve from time zero to infinite time.

Outcome measures

Outcome measures
Measure	Phase 1b: Cohort 1 n=3 Participants Gemcitabine at a dose of 1000 mg/m\^2 was administered over approximately 30 minutes IV on Days 1 and 8 of each cycle for a maximum of 4 cycles. Cisplatin at a dose of 75 mg/m\^2 was administered over approximately 120 minutes IV on Day 1 for a maximum of 4 cycles. Necitumumab at a dose of 800 mg was administered over approximately 50 minutes intravenously IV on Days 1 and 8 of each 3-week cycle.	Phase 1b: Cohort 2 n=6 Participants Gemcitabine at a dose of 1250 mg/m\^2 was administered over approximately 30 minutes IV on Days 1 and 8 of each cycle for a maximum of 4 cycles. Cisplatin at a dose of 75 mg/m\^2 was administered over approximately 120 minutes IV on Day 1 for a maximum of 4 cycles. Necitumumab at a dose of 800 mg was administered over approximately 50 minutes intravenously IV on Days 1 and 8 of each 3-week cycle.
Phase 1b: PK: Area Under the Serum Concentration-Time Curve From Time Zero to Infinite Time (AUC[0-infinity]) of Necitumumab Cycle 1	NA microgramhour per milliliter (µgh/mL) Geometric Coefficient of Variation NA Geometric Mean and Geometric Coefficient of Variation not figured due to an N of 2 and the individual minimum-maximum values = 39400-42900.	38900 microgramhour per milliliter (µgh/mL) Geometric Coefficient of Variation 28

SECONDARY outcome

Timeframe: Gemcitabine: C1D1: Predose, End-of-infusion and 0.5, 1, 2 h post-end-of-infusion; Cisplatin:C1D1: Predose, End-of-infusion and 3, 21, 93, 165 h post-end-of-infusion

Population: All enrolled participants who had adequate data to calculate at least 1 PK parameter during study Phase 1b. In cohort 1 (cisplatin), zero participants were analyzed because no data was collected for the outcome measure.

The AUC(0-infinity) is area under the plasma concentration-time curve from time zero to infinite time.

Outcome measures

Outcome measures
Measure	Phase 1b: Cohort 1 n=3 Participants Gemcitabine at a dose of 1000 mg/m\^2 was administered over approximately 30 minutes IV on Days 1 and 8 of each cycle for a maximum of 4 cycles. Cisplatin at a dose of 75 mg/m\^2 was administered over approximately 120 minutes IV on Day 1 for a maximum of 4 cycles. Necitumumab at a dose of 800 mg was administered over approximately 50 minutes intravenously IV on Days 1 and 8 of each 3-week cycle.	Phase 1b: Cohort 2 n=6 Participants Gemcitabine at a dose of 1250 mg/m\^2 was administered over approximately 30 minutes IV on Days 1 and 8 of each cycle for a maximum of 4 cycles. Cisplatin at a dose of 75 mg/m\^2 was administered over approximately 120 minutes IV on Day 1 for a maximum of 4 cycles. Necitumumab at a dose of 800 mg was administered over approximately 50 minutes intravenously IV on Days 1 and 8 of each 3-week cycle.
Phase 1b: PK: Area Under the Plasma Concentration-Time Curve From Time Zero to Infinite Time (AUC[0-infinity]) of Gemcitabine and Cisplatin Gemcitabine	8710 nanogramhour per milliliter (ngh/mL) Geometric Coefficient of Variation 7	13300 nanogramhour per milliliter (ngh/mL) Geometric Coefficient of Variation 19
Phase 1b: PK: Area Under the Plasma Concentration-Time Curve From Time Zero to Infinite Time (AUC[0-infinity]) of Gemcitabine and Cisplatin Cisplatin	—	NA nanogramhour per milliliter (ngh/mL) Geometric Coefficient of Variation NA In Cohort 2, summary statistics of t1/2 dependent parameters were not calculated as per the statistical analysis plan because n=1.

SECONDARY outcome

Timeframe: Predose Day 1 of Cycle 1, 2, 3, 4, and every 2 cycles after Cycle 5

Population: All enrolled participants who had adequate data to calculate at least 1 PK parameter during study Phase 2.

The minimum observed serum concentration (Ctrough) of Necitumumab was evaluated.

Outcome measures

Outcome measures
Measure	Phase 1b: Cohort 1 n=90 Participants Gemcitabine at a dose of 1000 mg/m\^2 was administered over approximately 30 minutes IV on Days 1 and 8 of each cycle for a maximum of 4 cycles. Cisplatin at a dose of 75 mg/m\^2 was administered over approximately 120 minutes IV on Day 1 for a maximum of 4 cycles. Necitumumab at a dose of 800 mg was administered over approximately 50 minutes intravenously IV on Days 1 and 8 of each 3-week cycle.	Phase 1b: Cohort 2 Gemcitabine at a dose of 1250 mg/m\^2 was administered over approximately 30 minutes IV on Days 1 and 8 of each cycle for a maximum of 4 cycles. Cisplatin at a dose of 75 mg/m\^2 was administered over approximately 120 minutes IV on Day 1 for a maximum of 4 cycles. Necitumumab at a dose of 800 mg was administered over approximately 50 minutes intravenously IV on Days 1 and 8 of each 3-week cycle.
Phase 2: PK: Minimum Concentration (Ctrough) of Necitumumab Dose 3	77.9 microgram per milliliter (µg/mL) Geometric Coefficient of Variation 30	—
Phase 2: PK: Minimum Concentration (Ctrough) of Necitumumab Dose 5	110 microgram per milliliter (µg/mL) Geometric Coefficient of Variation 32	—
Phase 2: PK: Minimum Concentration (Ctrough) of Necitumumab Dose 7	130 microgram per milliliter (µg/mL) Geometric Coefficient of Variation 36	—
Phase 2: PK: Minimum Concentration (Ctrough) of Necitumumab Dose 9	137 microgram per milliliter (µg/mL) Geometric Coefficient of Variation 41	—
Phase 2: PK: Minimum Concentration (Ctrough) of Necitumumab Dose 13	145 microgram per milliliter (µg/mL) Geometric Coefficient of Variation 48	—
Phase 2: PK: Minimum Concentration (Ctrough) of Necitumumab Dose 17	120 microgram per milliliter (µg/mL) Geometric Coefficient of Variation 59	—
Phase 2: PK: Minimum Concentration (Ctrough) of Necitumumab Dose 21	194 microgram per milliliter (µg/mL) Geometric Coefficient of Variation 44	—

SECONDARY outcome

Timeframe: Baseline up to 30 Days Post Last Infusion (estimated up to 39 months)

Population: All enrolled participants who received at least 1 dose of drug and had evaluable data for antibodies during study Phase 2.

A participant was considered to have an anti-Necitumumab antibody response if anti-drug antibodies (ADA) were detected at any time point.

Outcome measures

Outcome measures
Measure	Phase 1b: Cohort 1 n=90 Participants Gemcitabine at a dose of 1000 mg/m\^2 was administered over approximately 30 minutes IV on Days 1 and 8 of each cycle for a maximum of 4 cycles. Cisplatin at a dose of 75 mg/m\^2 was administered over approximately 120 minutes IV on Day 1 for a maximum of 4 cycles. Necitumumab at a dose of 800 mg was administered over approximately 50 minutes intravenously IV on Days 1 and 8 of each 3-week cycle.	Phase 1b: Cohort 2 Gemcitabine at a dose of 1250 mg/m\^2 was administered over approximately 30 minutes IV on Days 1 and 8 of each cycle for a maximum of 4 cycles. Cisplatin at a dose of 75 mg/m\^2 was administered over approximately 120 minutes IV on Day 1 for a maximum of 4 cycles. Necitumumab at a dose of 800 mg was administered over approximately 50 minutes intravenously IV on Days 1 and 8 of each 3-week cycle.
Phase 2: Number of Participants With Serum Anti-Necitumumab Antibody Assessment (Immunogenicity)	4 Participants	—

Adverse Events

Phase 1b: Cohort 1

Serious events: 1 serious events

Other events: 3 other events

Deaths: 0 deaths

Phase 1b: Cohort 2

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Phase 2: GC+N (Gemcitabine, Cisplatin + Necitumumab)

Serious events: 32 serious events

Other events: 90 other events

Deaths: 63 deaths

Phase 2: GC (Gemcitabine, Cisplatin)

Serious events: 22 serious events

Other events: 91 other events

Deaths: 74 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