Trial Outcomes & Findings for Study of IMC-11F8 in Participants With Advanced Solid Tumors (NCT NCT01088464)

Last Updated: 2017-02-03

Results Overview

Data presented are the number of participants who experienced 1 or more TEAEs or SAEs regardless of causality. An adverse event was considered as TEAE if it occurred any time after the administration of the first dose of study drug or up to 30 days after the last dose of study treatment or if it occurred prior to the first dose and worsened while on treatment. A summary of SAEs and other non-SAEs regardless of causality is located in the Reported Adverse Events module.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

15 participants

Primary outcome timeframe

Baseline up to 24 weeks plus 30 days post last dose of study drug

Results posted on

2017-02-03

Participant Flow

The study had 3 cohorts and dose escalation in successive cohorts was to occur once all the participants completed 1 cycle of therapy. A completed participant was either a participant who completed the initial 6-week treatment period (Cycle 1) or a participant who discontinued therapy for an IMC-11F8 (Necitumumab) related toxicity during Cycle 1.

Participant milestones

Participant milestones
Measure	Cohort 1: Necitumumab Necitumumab 600 milligrams (mg) administered intravenously on Days 1 and 8 every 3 weeks of a 6-week cycle. After Cycle 1, participants showing objective response or stable disease were to receive necitumumab at same dose and schedule until disease progression or other withdrawal criteria were met.	Cohort 2: Necitumumab Necitumumab 800 mg administered intravenously every 2 weeks of a 6-week cycle. After Cycle 1, participants showing objective response or stable disease were to receive necitumumab at same dose and schedule until disease progression or other withdrawal criteria were met.	Cohort 3: Necitumumab Necitumumab 800 mg administered intravenously on Days 1 and 8 every 3 weeks of a 6-week cycle. After Cycle 1, participants showing objective response or stable disease were to receive necitumumab at same dose and schedule until disease progression or other withdrawal criteria were met.
Overall Study STARTED	3	6	6
Overall Study Received Any Quantity of Study Drug	3	6	6
Overall Study COMPLETED	3	6	6
Overall Study NOT COMPLETED	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Study of IMC-11F8 in Participants With Advanced Solid Tumors

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Cohort 1: Necitumumab n=3 Participants Necitumumab 600 mg administered intravenously on Days 1 and 8 every 3 weeks of a 6-week cycle. After Cycle 1, participants showing objective response or stable disease were to receive necitumumab at same dose and schedule until disease progression or other withdrawal criteria were met.	Cohort 2: Necitumumab n=6 Participants Necitumumab 800 mg administered intravenously every 2 weeks of a 6-week cycle. After Cycle 1, participants showing objective response or stable disease were to receive necitumumab at same dose and schedule until disease progression or other withdrawal criteria were met.	Cohort 3: Necitumumab n=6 Participants Necitumumab 800 mg administered intravenously on Days 1 and 8 every 3 weeks of a 6-week cycle. After Cycle 1, participants showing objective response or stable disease were to receive necitumumab at same dose and schedule until disease progression or other withdrawal criteria were met.	Total n=15 Participants Total of all reporting groups
Age, Continuous	57.2 years FULL_RANGE 20.02 • n=93 Participants	64.5 years FULL_RANGE 4.51 • n=4 Participants	56.7 years FULL_RANGE 9.50 • n=27 Participants	61.2 years FULL_RANGE 10.72 • n=483 Participants
Gender Female	1 Participants n=93 Participants	3 Participants n=4 Participants	4 Participants n=27 Participants	8 Participants n=483 Participants
Gender Male	2 Participants n=93 Participants	3 Participants n=4 Participants	2 Participants n=27 Participants	7 Participants n=483 Participants
Race/Ethnicity, Customized Japanese	3 participants n=93 Participants	6 participants n=4 Participants	6 participants n=27 Participants	15 participants n=483 Participants
Region of Enrollment Japan	3 participants n=93 Participants	6 participants n=4 Participants	6 participants n=27 Participants	15 participants n=483 Participants
Eastern Cooperative Oncology Group performance status (ECOG PS) 0 = Fully Active	1 participants n=93 Participants	1 participants n=4 Participants	4 participants n=27 Participants	6 participants n=483 Participants
Eastern Cooperative Oncology Group performance status (ECOG PS) 1 = Ambulatory, Restricted Work Activity	2 participants n=93 Participants	5 participants n=4 Participants	2 participants n=27 Participants	9 participants n=483 Participants

PRIMARY outcome

Timeframe: Baseline up to 24 weeks plus 30 days post last dose of study drug

Population: All participants who received any quantity of study drug.

Outcome measures

Outcome measures
Measure	Cohort 1: Necitumumab n=3 Participants Necitumumab 600 mg administered intravenously on Days 1 and 8 every 3 weeks of a 6-week cycle. After Cycle 1, participants showing objective response or stable disease were to receive necitumumab at same dose and schedule until disease progression or other withdrawal criteria were met.	Cohort 2: Necitumumab n=6 Participants Necitumumab 800 mg administered intravenously every 2 weeks of a 6-week cycle. After Cycle 1, participants showing objective response or stable disease were to receive necitumumab at same dose and schedule until disease progression or other withdrawal criteria were met.	Cohort 3: Necitumumab n=6 Participants Necitumumab 800 mg administered intravenously on Days 1 and 8 every 3 weeks of a 6-week cycle. After Cycle 1, participants showing objective response or stable disease were to receive necitumumab at same dose and schedule until disease progression or other withdrawal criteria were met.
Number of Participants With 1 or More Treatment-Emergent Adverse Events (TEAEs) or Serious Adverse Events (SAEs) TEAEs	3 participants	6 participants	6 participants
Number of Participants With 1 or More Treatment-Emergent Adverse Events (TEAEs) or Serious Adverse Events (SAEs) SAEs	1 participants	0 participants	1 participants

PRIMARY outcome

Timeframe: Cycle 1, Day 1; Cohorts 1 and 3: predose, immediately after end of infusion, 0.5, 1, 2, 6, 24, 96 and 168 hours (h) after end of infusion. Cohort 2: predose, immediately after infusion, 0.5, 1, 2, 4, 8, 24, 48, 96, 168, 264 and 336 h after end of infusion

Population: All participants who received single dose of study drug and had Cmax values for Day 1 of Cycle 1.

Outcome measures

Outcome measures
Measure	Cohort 1: Necitumumab n=3 Participants Necitumumab 600 mg administered intravenously on Days 1 and 8 every 3 weeks of a 6-week cycle. After Cycle 1, participants showing objective response or stable disease were to receive necitumumab at same dose and schedule until disease progression or other withdrawal criteria were met.	Cohort 2: Necitumumab n=6 Participants Necitumumab 800 mg administered intravenously every 2 weeks of a 6-week cycle. After Cycle 1, participants showing objective response or stable disease were to receive necitumumab at same dose and schedule until disease progression or other withdrawal criteria were met.	Cohort 3: Necitumumab n=6 Participants Necitumumab 800 mg administered intravenously on Days 1 and 8 every 3 weeks of a 6-week cycle. After Cycle 1, participants showing objective response or stable disease were to receive necitumumab at same dose and schedule until disease progression or other withdrawal criteria were met.
Pharmacokinetics (PK): Maximum Plasma Concentration (Cmax) of Necitumumab After a Single Dose	306 micrograms per milliliter (µg/mL) Geometric Coefficient of Variation 29	417 micrograms per milliliter (µg/mL) Geometric Coefficient of Variation 46	352 micrograms per milliliter (µg/mL) Geometric Coefficient of Variation 20

PRIMARY outcome

Timeframe: Cycle 1, Day 29; For Cohorts 1, 2 and 3: predose (prior to fourth infusion for Cohorts 1 and 3; prior to third infusion for Cohort 2), immediately after end of infusion, 0.5, 1, 2, 4, 8, 24, 48, 96, 168, 264 and 336 h after end of infusion

Population: All participants who received multiple doses of study drug and had Cmax values for Day 29 of Cycle 1.

Cmax at steady state (after the last dose of the initial 6-week treatment cycle).

Outcome measures

Outcome measures
Measure	Cohort 1: Necitumumab n=3 Participants Necitumumab 600 mg administered intravenously on Days 1 and 8 every 3 weeks of a 6-week cycle. After Cycle 1, participants showing objective response or stable disease were to receive necitumumab at same dose and schedule until disease progression or other withdrawal criteria were met.	Cohort 2: Necitumumab n=6 Participants Necitumumab 800 mg administered intravenously every 2 weeks of a 6-week cycle. After Cycle 1, participants showing objective response or stable disease were to receive necitumumab at same dose and schedule until disease progression or other withdrawal criteria were met.	Cohort 3: Necitumumab n=6 Participants Necitumumab 800 mg administered intravenously on Days 1 and 8 every 3 weeks of a 6-week cycle. After Cycle 1, participants showing objective response or stable disease were to receive necitumumab at same dose and schedule until disease progression or other withdrawal criteria were met.
PK: Cmax of Necitumumab After Multiple Doses	396 µg/mL Geometric Coefficient of Variation 5	523 µg/mL Geometric Coefficient of Variation 17	629 µg/mL Geometric Coefficient of Variation 16

PRIMARY outcome

Timeframe: Cycle 1; Cohorts 1, 2 and 3: prior to second infusion

Population: All participants who received single dose of study drug and had Cmin serum concentrations analyzed prior to administration of second dose.

Cmin is defined as the minimum concentration the drug achieved after administration of first infusion and prior to the administration of second infusion.

Outcome measures

Outcome measures
Measure	Cohort 1: Necitumumab n=3 Participants Necitumumab 600 mg administered intravenously on Days 1 and 8 every 3 weeks of a 6-week cycle. After Cycle 1, participants showing objective response or stable disease were to receive necitumumab at same dose and schedule until disease progression or other withdrawal criteria were met.	Cohort 2: Necitumumab n=6 Participants Necitumumab 800 mg administered intravenously every 2 weeks of a 6-week cycle. After Cycle 1, participants showing objective response or stable disease were to receive necitumumab at same dose and schedule until disease progression or other withdrawal criteria were met.	Cohort 3: Necitumumab n=6 Participants Necitumumab 800 mg administered intravenously on Days 1 and 8 every 3 weeks of a 6-week cycle. After Cycle 1, participants showing objective response or stable disease were to receive necitumumab at same dose and schedule until disease progression or other withdrawal criteria were met.
PK: Minimum Concentration (Cmin) of Necitumumab After a Single Dose	86.0 µg/mL Geometric Coefficient of Variation 10	72.9 µg/mL Geometric Coefficient of Variation 24	127 µg/mL Geometric Coefficient of Variation 18

PRIMARY outcome

Timeframe: Cycle 1; Cohorts 1and 3: prior to fourth infusion. Cohort 2: prior to third infusion

Population: All participants who received multiple doses of study drug and had Cmin serum concentrations prior to last dose of Cycle 1.

Cmin was calculated prior to the last dose of the initial 6-week treatment cycle.

Outcome measures

Outcome measures
Measure	Cohort 1: Necitumumab n=3 Participants Necitumumab 600 mg administered intravenously on Days 1 and 8 every 3 weeks of a 6-week cycle. After Cycle 1, participants showing objective response or stable disease were to receive necitumumab at same dose and schedule until disease progression or other withdrawal criteria were met.	Cohort 2: Necitumumab n=6 Participants Necitumumab 800 mg administered intravenously every 2 weeks of a 6-week cycle. After Cycle 1, participants showing objective response or stable disease were to receive necitumumab at same dose and schedule until disease progression or other withdrawal criteria were met.	Cohort 3: Necitumumab n=5 Participants Necitumumab 800 mg administered intravenously on Days 1 and 8 every 3 weeks of a 6-week cycle. After Cycle 1, participants showing objective response or stable disease were to receive necitumumab at same dose and schedule until disease progression or other withdrawal criteria were met.
PK: Cmin of Necitumumab After Multiple Doses	108 µg/mL Geometric Coefficient of Variation 23	136 µg/mL Geometric Coefficient of Variation 22	220 µg/mL Geometric Coefficient of Variation 16

PRIMARY outcome

Timeframe: Cycle 1, Day 1; Cohorts 1 and 3: predose, immediately after end of infusion, 0.5, 1, 2, 6, 24, 96 and 168 h after end of infusion. Cohort 2: predose, immediately after end of infusion, 0.5, 1, 2, 4, 8, 24, 48, 96, 168, 264 and 336 h after end of infusion

Population: All participants who received single dose of study drug and had evaluable AUC(0-∞) values for Day 1 of Cycle 1.

Outcome measures

Outcome measures
Measure	Cohort 1: Necitumumab n=3 Participants Necitumumab 600 mg administered intravenously on Days 1 and 8 every 3 weeks of a 6-week cycle. After Cycle 1, participants showing objective response or stable disease were to receive necitumumab at same dose and schedule until disease progression or other withdrawal criteria were met.	Cohort 2: Necitumumab n=6 Participants Necitumumab 800 mg administered intravenously every 2 weeks of a 6-week cycle. After Cycle 1, participants showing objective response or stable disease were to receive necitumumab at same dose and schedule until disease progression or other withdrawal criteria were met.	Cohort 3: Necitumumab n=6 Participants Necitumumab 800 mg administered intravenously on Days 1 and 8 every 3 weeks of a 6-week cycle. After Cycle 1, participants showing objective response or stable disease were to receive necitumumab at same dose and schedule until disease progression or other withdrawal criteria were met.
PK: Area Under the Concentration-Time Curve From Time 0 to Last Time Point [AUC (0-tlast)] of Necitumumab After a Single Dose	23100 microgramshour/milliliter (µgh/mL) Geometric Coefficient of Variation 16	50100 microgramshour/milliliter (µgh/mL) Geometric Coefficient of Variation 24	31300 microgramshour/milliliter (µgh/mL) Geometric Coefficient of Variation 17

PRIMARY outcome

Population: All participants who received single dose of study drug and had evaluable AUC(0-∞) values for Day 1 of Cycle 1. No participant of Cohorts 1 and 3 were analyzed for AUC(0-∞) on Day 1 of Cycle 1, due to fraction of data outside tlast \>30%

AUC(0-∞) was calculated only for participants in Cohort 2 as the percentage of AUC extrapolated beyond tlast was greater than 30% for all the remaining participants.

Outcome measures

Outcome measures
Measure	Cohort 1: Necitumumab Necitumumab 600 mg administered intravenously on Days 1 and 8 every 3 weeks of a 6-week cycle. After Cycle 1, participants showing objective response or stable disease were to receive necitumumab at same dose and schedule until disease progression or other withdrawal criteria were met.	Cohort 2: Necitumumab n=3 Participants Necitumumab 800 mg administered intravenously every 2 weeks of a 6-week cycle. After Cycle 1, participants showing objective response or stable disease were to receive necitumumab at same dose and schedule until disease progression or other withdrawal criteria were met.	Cohort 3: Necitumumab Necitumumab 800 mg administered intravenously on Days 1 and 8 every 3 weeks of a 6-week cycle. After Cycle 1, participants showing objective response or stable disease were to receive necitumumab at same dose and schedule until disease progression or other withdrawal criteria were met.
PK: Area Under the Concentration-Time Curve From Time 0 to Infinity [AUC(0-∞)] of Necitumumab After a Single Dose	—	66700 µg*h/mL Geometric Coefficient of Variation 21	—

PRIMARY outcome

Population: All the participants who received multiple doses of study drug and had AUC(0-336) values for Day 29 of Cycle 1.

Steady state AUC(0-336) values are reported.

Outcome measures

Outcome measures
Measure	Cohort 1: Necitumumab n=3 Participants Necitumumab 600 mg administered intravenously on Days 1 and 8 every 3 weeks of a 6-week cycle. After Cycle 1, participants showing objective response or stable disease were to receive necitumumab at same dose and schedule until disease progression or other withdrawal criteria were met.	Cohort 2: Necitumumab n=6 Participants Necitumumab 800 mg administered intravenously every 2 weeks of a 6-week cycle. After Cycle 1, participants showing objective response or stable disease were to receive necitumumab at same dose and schedule until disease progression or other withdrawal criteria were met.	Cohort 3: Necitumumab n=5 Participants Necitumumab 800 mg administered intravenously on Days 1 and 8 every 3 weeks of a 6-week cycle. After Cycle 1, participants showing objective response or stable disease were to receive necitumumab at same dose and schedule until disease progression or other withdrawal criteria were met.
PK: Area Under the Concentration-Time Curve From Time 0 to 336 h Postdose [AUC(0-336)] of Necitumumab After Multiple Doses	56300 µg*h/mL Geometric Coefficient of Variation 21	81400 µg*h/mL Geometric Coefficient of Variation 19	105000 µg*h/mL Geometric Coefficient of Variation 12

PRIMARY outcome

Population: All participants who received single dose of study drug and had t½ values for Day 1 of Cycle 1.

The t½ is defined as the time taken for study drug in blood to decrease to half of its concentration.

Outcome measures

Outcome measures
Measure	Cohort 1: Necitumumab n=3 Participants Necitumumab 600 mg administered intravenously on Days 1 and 8 every 3 weeks of a 6-week cycle. After Cycle 1, participants showing objective response or stable disease were to receive necitumumab at same dose and schedule until disease progression or other withdrawal criteria were met.	Cohort 2: Necitumumab n=6 Participants Necitumumab 800 mg administered intravenously every 2 weeks of a 6-week cycle. After Cycle 1, participants showing objective response or stable disease were to receive necitumumab at same dose and schedule until disease progression or other withdrawal criteria were met.	Cohort 3: Necitumumab n=6 Participants Necitumumab 800 mg administered intravenously on Days 1 and 8 every 3 weeks of a 6-week cycle. After Cycle 1, participants showing objective response or stable disease were to receive necitumumab at same dose and schedule until disease progression or other withdrawal criteria were met.
PK: Half-Life (t½) of Necitumumab After a Single Dose	126 h Geometric Coefficient of Variation 14	207 h Geometric Coefficient of Variation 31	146 h Geometric Coefficient of Variation 18

PRIMARY outcome

Population: All the participants who received multiple doses of study drug and had t½ values for Day 29 of Cycle 1.

The t½ is defined as the time taken for study drug in blood to decrease to half of its concentration.

Outcome measures

Outcome measures
Measure	Cohort 1: Necitumumab n=3 Participants Necitumumab 600 mg administered intravenously on Days 1 and 8 every 3 weeks of a 6-week cycle. After Cycle 1, participants showing objective response or stable disease were to receive necitumumab at same dose and schedule until disease progression or other withdrawal criteria were met.	Cohort 2: Necitumumab n=5 Participants Necitumumab 800 mg administered intravenously every 2 weeks of a 6-week cycle. After Cycle 1, participants showing objective response or stable disease were to receive necitumumab at same dose and schedule until disease progression or other withdrawal criteria were met.	Cohort 3: Necitumumab n=5 Participants Necitumumab 800 mg administered intravenously on Days 1 and 8 every 3 weeks of a 6-week cycle. After Cycle 1, participants showing objective response or stable disease were to receive necitumumab at same dose and schedule until disease progression or other withdrawal criteria were met.
PK: t½ of Necitumumab After Multiple Doses	190 h Geometric Coefficient of Variation 36	233 h Geometric Coefficient of Variation 18	286 h Geometric Coefficient of Variation 18

PRIMARY outcome

Population: All the participants who received single dose of study drug and had CL values for Day 1 of Cycle 1. No participant of Cohorts 1 and 3 were analyzed for CL on Day 1 of Cycle 1, due to fraction of data outside tlast \>30%

CL is defined as the volume of plasma that is cleared of study drug per unit time. CL was not analyzed for participants in Cohorts 1 and 3 as CL is derived from AUC(0-∞). AUC(0-∞) was calculated only for participants in Cohort 2 as the percentage of AUC extrapolated beyond tlast was greater than 30% for the remaining participants.

Outcome measures

Outcome measures
Measure	Cohort 1: Necitumumab Necitumumab 600 mg administered intravenously on Days 1 and 8 every 3 weeks of a 6-week cycle. After Cycle 1, participants showing objective response or stable disease were to receive necitumumab at same dose and schedule until disease progression or other withdrawal criteria were met.	Cohort 2: Necitumumab n=3 Participants Necitumumab 800 mg administered intravenously every 2 weeks of a 6-week cycle. After Cycle 1, participants showing objective response or stable disease were to receive necitumumab at same dose and schedule until disease progression or other withdrawal criteria were met.	Cohort 3: Necitumumab Necitumumab 800 mg administered intravenously on Days 1 and 8 every 3 weeks of a 6-week cycle. After Cycle 1, participants showing objective response or stable disease were to receive necitumumab at same dose and schedule until disease progression or other withdrawal criteria were met.
PK: Clearance (CL) of Necitumumab After a Single Dose	—	12.0 milliliters per hour (mL/h) Geometric Coefficient of Variation 21	—

PRIMARY outcome

Population: All the participants who received multiple doses of study drug and had CL values for Day 29 of Cycle 1. CL of necitumumab was not assessed for participants in Cohorts 1 and 3, due to the irregular dosing regimen.

CL is defined as the volume of plasma that is cleared of study drug per unit time. Data did not allow calculation of CL for participants in Cohorts 1 and 3.

Outcome measures

Outcome measures
Measure	Cohort 1: Necitumumab Necitumumab 600 mg administered intravenously on Days 1 and 8 every 3 weeks of a 6-week cycle. After Cycle 1, participants showing objective response or stable disease were to receive necitumumab at same dose and schedule until disease progression or other withdrawal criteria were met.	Cohort 2: Necitumumab n=6 Participants Necitumumab 800 mg administered intravenously every 2 weeks of a 6-week cycle. After Cycle 1, participants showing objective response or stable disease were to receive necitumumab at same dose and schedule until disease progression or other withdrawal criteria were met.	Cohort 3: Necitumumab Necitumumab 800 mg administered intravenously on Days 1 and 8 every 3 weeks of a 6-week cycle. After Cycle 1, participants showing objective response or stable disease were to receive necitumumab at same dose and schedule until disease progression or other withdrawal criteria were met.
PK: CL of Necitumumab After Multiple Doses	—	9.83 mL/h Geometric Coefficient of Variation 19	—

PRIMARY outcome

Population: All participants who received single dose of study drug and had Vss values for Day 1 of Cycle 1. Vss of necitumumab was not assessed for participants in Cohorts 1 and 3, due to the irregular dosing regimen.

Vss is that amount of plasma in which the study drug needs to be dissolved to attain a steady state drug concentration. Vss was not analyzed for participants in Cohorts 1 and 3 as Vss is derived from AUC (0-∞). AUC(0-∞) was calculated only for participants in Cohort 2 as the percentage of AUC extrapolated beyond tlast was greater than 30% for the remaining participants.

Outcome measures

Outcome measures
Measure	Cohort 1: Necitumumab Necitumumab 600 mg administered intravenously on Days 1 and 8 every 3 weeks of a 6-week cycle. After Cycle 1, participants showing objective response or stable disease were to receive necitumumab at same dose and schedule until disease progression or other withdrawal criteria were met.	Cohort 2: Necitumumab n=3 Participants Necitumumab 800 mg administered intravenously every 2 weeks of a 6-week cycle. After Cycle 1, participants showing objective response or stable disease were to receive necitumumab at same dose and schedule until disease progression or other withdrawal criteria were met.	Cohort 3: Necitumumab Necitumumab 800 mg administered intravenously on Days 1 and 8 every 3 weeks of a 6-week cycle. After Cycle 1, participants showing objective response or stable disease were to receive necitumumab at same dose and schedule until disease progression or other withdrawal criteria were met.
PK: Steady-State Volume of Distribution (Vss) of Necitumumab After Single Dose	—	2780 milliliters (mL) Geometric Coefficient of Variation 31	—

PRIMARY outcome

Population: All participants who received multiple doses of study drug and had Vss values for Day 29 of Cycle 1. Vss of necitumumab was not assessed for participants in Cohorts 1 and 3, due to the irregular dosing regimen.

Vss is that amount of plasma in which the study drug needs to be dissolved to attain a steady state drug concentration. Data did not allow calculation of Vss for participants in Cohorts 1 and 3.

Outcome measures

Outcome measures
Measure	Cohort 1: Necitumumab Necitumumab 600 mg administered intravenously on Days 1 and 8 every 3 weeks of a 6-week cycle. After Cycle 1, participants showing objective response or stable disease were to receive necitumumab at same dose and schedule until disease progression or other withdrawal criteria were met.	Cohort 2: Necitumumab n=5 Participants Necitumumab 800 mg administered intravenously every 2 weeks of a 6-week cycle. After Cycle 1, participants showing objective response or stable disease were to receive necitumumab at same dose and schedule until disease progression or other withdrawal criteria were met.	Cohort 3: Necitumumab Necitumumab 800 mg administered intravenously on Days 1 and 8 every 3 weeks of a 6-week cycle. After Cycle 1, participants showing objective response or stable disease were to receive necitumumab at same dose and schedule until disease progression or other withdrawal criteria were met.
PK: Vss of Necitumumab After Multiple Doses	—	3370 mL Geometric Coefficient of Variation 21	—

SECONDARY outcome

Timeframe: For Cohorts 1, 2 and 3: Prior to first infusions of Cycles 1, 2, and 4 and at the 30-day follow-up visit (+7 days) after the last dose of study drug

Population: All participants who received any quantity of study drug.

Treatment-emergent samples were defined as samples which showed at least 4-fold difference (2 dilution increase) at post-baseline in IK titer over the baseline titer, or participants who tested negative at baseline and positive post-baseline (at titer of ≥1:20).

Outcome measures

Outcome measures
Measure	Cohort 1: Necitumumab n=3 Participants Necitumumab 600 mg administered intravenously on Days 1 and 8 every 3 weeks of a 6-week cycle. After Cycle 1, participants showing objective response or stable disease were to receive necitumumab at same dose and schedule until disease progression or other withdrawal criteria were met.	Cohort 2: Necitumumab n=6 Participants Necitumumab 800 mg administered intravenously every 2 weeks of a 6-week cycle. After Cycle 1, participants showing objective response or stable disease were to receive necitumumab at same dose and schedule until disease progression or other withdrawal criteria were met.	Cohort 3: Necitumumab n=6 Participants Necitumumab 800 mg administered intravenously on Days 1 and 8 every 3 weeks of a 6-week cycle. After Cycle 1, participants showing objective response or stable disease were to receive necitumumab at same dose and schedule until disease progression or other withdrawal criteria were met.
Immunogenicity (IK): Number of Participants With Treatment-Emergent Anti-IMC-11F8 Antibodies Positive for Anti-Necitumumab Antibodies	0 participants	0 participants	0 participants
Immunogenicity (IK): Number of Participants With Treatment-Emergent Anti-IMC-11F8 Antibodies Negative for Anti-Necitumumab Antibodies	3 participants	6 participants	6 participants

Adverse Events

Cohort 1: Necitumumab

Serious events: 1 serious events

Other events: 3 other events

Deaths: 0 deaths

Cohort 2: Necitumumab

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Cohort 3: Necitumumab

Serious events: 1 serious events

Other events: 6 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Cohort 1: Necitumumab n=3 participants at risk Necitumumab 600 mg administered intravenously on Days 1 and 8 every 3 weeks of a 6-week cycle. After Cycle 1, participants showing objective response or stable disease were to receive necitumumab at same dose and schedule until disease progression or other withdrawal criteria were met.	Cohort 2: Necitumumab n=6 participants at risk Necitumumab 800 mg administered intravenously every 2 weeks of a 6-week cycle. After Cycle 1, participants showing objective response or stable disease were to receive necitumumab at same dose and schedule until disease progression or other withdrawal criteria were met.	Cohort 3: Necitumumab n=6 participants at risk Necitumumab 800 mg administered intravenously on Days 1 and 8 every 3 weeks of a 6-week cycle. After Cycle 1, participants showing objective response or stable disease were to receive necitumumab at same dose and schedule until disease progression or other withdrawal criteria were met.
Hepatobiliary disorders Hepatic function abnormal	0.00% 0/3 • Baseline up to 24 weeks plus 30 days post last dose of study drug	0.00% 0/6 • Baseline up to 24 weeks plus 30 days post last dose of study drug	16.7% 1/6 • Number of events 1 • Baseline up to 24 weeks plus 30 days post last dose of study drug
Respiratory, thoracic and mediastinal disorders Dyspnoea	33.3% 1/3 • Number of events 1 • Baseline up to 24 weeks plus 30 days post last dose of study drug	0.00% 0/6 • Baseline up to 24 weeks plus 30 days post last dose of study drug	0.00% 0/6 • Baseline up to 24 weeks plus 30 days post last dose of study drug
Respiratory, thoracic and mediastinal disorders Oropharyngeal discomfort	33.3% 1/3 • Number of events 1 • Baseline up to 24 weeks plus 30 days post last dose of study drug	0.00% 0/6 • Baseline up to 24 weeks plus 30 days post last dose of study drug	0.00% 0/6 • Baseline up to 24 weeks plus 30 days post last dose of study drug

Other adverse events

Additional Information

Chief Medical Officer

Eli Lilly and Company

Phone: 800-545-5979

Results disclosure agreements

Principal investigator is a sponsor employee Investigators agreed to delay independently publishing or disclosing data, findings or conclusions from the study except as part of a multi-center publication. Upon study completion or if the draft publication is not produced within approximately 6 months of the final report of the study results, investigators may independently publish, subject to confidential information review/redaction by sponsor. The sponsor may request publication delay up to 90 days to seek patent protection.
Publication restrictions are in place

Restriction type: OTHER