Trial Outcomes & Findings for A Study of IMC-A12 (Cixutumumab) With and Without Other Standard Chemotherapies in Participants With Lung Cancer Who Have Not Received Chemotherapy Before (NCT NCT00870870)

Last Updated: 2018-06-01

Results Overview

ORR was defined as the percentage of participants achieving either CR or PR. Response was defined using Response Evaluation Criteria in Solid Tumors (RECIST), version (v) 1.0 criteria. CR was defined as the disappearance of all target and non-target lesions and the normalization of the tumour marker level. PR was defined as having at least a 30% decrease in sum of longest diameter (LD) of target lesions, taking as reference the baseline sum LD. Percentage of participants is calculated as a total number of participants with CR or PR / total number of participants treated \* 100.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

64 participants

Primary outcome timeframe

Randomization to measured progressive disease (PD) (up to 16.9 months)

Results posted on

2018-06-01

Participant Flow

Participant milestones

Participant milestones
Measure	Gemcitabine/Carboplatin/Cetuximab (GCC) Gemcitabine: 1000 milligrams per square meter (mg/m\^2) on Days 1 and 8 of each 3-week cycle for a total of 6 cycles (18 weeks). Cetuximab: Initial dose of 400 mg/m\^2 on Day 1 of Cycle 1, and subsequent doses of 250 mg/m\^2 once every week (Q1W) of each 3-week cycle for a total of 6 cycles (18 weeks). Later administered at 500 mg/m\^2 once every 2 weeks (Q2W) in the subsequent cycles (2-week cycles). Carboplatin: Area under the curve (AUC) = 5 on Day 1 of each 3-week cycle for a total of 6 cycles (18 weeks). Treatment was continued until disease progression, unacceptable toxicity, withdrawal of consent or any other discontinuation criteria were met.	GCC Plus Cixutumumab Gemcitabine: 1000 mg/m\^2 on Days 1 and 8 of each 3-week cycle for a total of 6 cycles (18 weeks). Cetuximab: Initial dose of 400 mg/m\^2 on Day 1 of Cycle 1 and subsequent doses of 250 mg/m\^2 Q1W of each 3-week cycle for a total of 6 cycles (18 weeks). Later administered at 500 mg/m\^2 Q2W in the subsequent cycles (2-week cycles). Carboplatin: AUC = 5 on Day 1 of each 3-week cycle for a total of 6 cycles (18 weeks). Cixutumumab: 6 milligrams per kilogram (mg/kg) intravenous (IV) infusion Q1W on Days 1, 8, and 15 of each 3-week cycle for a total of 6 cycles (18 weeks). Later administered at 10 mg/kg IV Q2W in the subsequent cycles (2-week cycles). Treatment was continued until disease progression, unacceptable toxicity, withdrawal of consent or any other discontinuation criteria were met.	Gemcitabine/Cisplatin/Cetuximab (GCiC) Gemcitabine: 1000 mg/m\^2 on Days 1 and 8 of each 3-week cycle for a total of 6 cycles (18 weeks). Cisplatin: 75 mg/m\^2 on Day 1 of each 3-week cycle for a total of 6 cycles (18 weeks). Cetuximab: Initial dose of 400 mg/m\^2 on Day 1 of Cycle 1 and subsequent doses of 250 mg/m\^2 Q1W of each 3-week cycle for a total of 6 cycles (18 weeks). Later administered at 500 mg/m\^2 Q2W in the subsequent cycles (2-week cycles). Treatment was continued until disease progression, unacceptable toxicity, withdrawal of consent or any other discontinuation criteria were met.	GCiC Plus Cixutumumab Gemcitabine: 1000 mg/m\^2 on Days 1 and 8 of each 3-week cycle for a total of 6 cycles (18 weeks). Cisplatin: 75 mg/m\^2 on Day 1 of each 3-week cycle for a total of 6 cycles (18 weeks). Cetuximab: Initial dose of 400 mg/m\^2 on Day 1 of Cycle 1 and subsequent doses of 250 mg/m\^2 Q1W of each 3-week cycle for a total of 6 cycles (18 weeks). Later administered at 500 mg/m\^2 Q2W in the subsequent cycles (2-week cycles). Cixutumumab: 6 mg/kg IV infusion Q1W on Days 1, 8, and 15 of each 3-week cycle for a total of 6 cycles (18 weeks). Later administered at 10 mg/kg IV Q2W in the subsequent cycles (2-week cycles). Treatment was continued until disease progression, unacceptable toxicity, withdrawal of consent or any other discontinuation criteria were met.
Overall Study STARTED	4	6	29	25
Overall Study COMPLETED	4	5	26	20
Overall Study NOT COMPLETED	0	1	3	5

Reasons for withdrawal

Reasons for withdrawal
Measure	Gemcitabine/Carboplatin/Cetuximab (GCC) Gemcitabine: 1000 milligrams per square meter (mg/m\^2) on Days 1 and 8 of each 3-week cycle for a total of 6 cycles (18 weeks). Cetuximab: Initial dose of 400 mg/m\^2 on Day 1 of Cycle 1, and subsequent doses of 250 mg/m\^2 once every week (Q1W) of each 3-week cycle for a total of 6 cycles (18 weeks). Later administered at 500 mg/m\^2 once every 2 weeks (Q2W) in the subsequent cycles (2-week cycles). Carboplatin: Area under the curve (AUC) = 5 on Day 1 of each 3-week cycle for a total of 6 cycles (18 weeks). Treatment was continued until disease progression, unacceptable toxicity, withdrawal of consent or any other discontinuation criteria were met.	GCC Plus Cixutumumab Gemcitabine: 1000 mg/m\^2 on Days 1 and 8 of each 3-week cycle for a total of 6 cycles (18 weeks). Cetuximab: Initial dose of 400 mg/m\^2 on Day 1 of Cycle 1 and subsequent doses of 250 mg/m\^2 Q1W of each 3-week cycle for a total of 6 cycles (18 weeks). Later administered at 500 mg/m\^2 Q2W in the subsequent cycles (2-week cycles). Carboplatin: AUC = 5 on Day 1 of each 3-week cycle for a total of 6 cycles (18 weeks). Cixutumumab: 6 milligrams per kilogram (mg/kg) intravenous (IV) infusion Q1W on Days 1, 8, and 15 of each 3-week cycle for a total of 6 cycles (18 weeks). Later administered at 10 mg/kg IV Q2W in the subsequent cycles (2-week cycles). Treatment was continued until disease progression, unacceptable toxicity, withdrawal of consent or any other discontinuation criteria were met.	Gemcitabine/Cisplatin/Cetuximab (GCiC) Gemcitabine: 1000 mg/m\^2 on Days 1 and 8 of each 3-week cycle for a total of 6 cycles (18 weeks). Cisplatin: 75 mg/m\^2 on Day 1 of each 3-week cycle for a total of 6 cycles (18 weeks). Cetuximab: Initial dose of 400 mg/m\^2 on Day 1 of Cycle 1 and subsequent doses of 250 mg/m\^2 Q1W of each 3-week cycle for a total of 6 cycles (18 weeks). Later administered at 500 mg/m\^2 Q2W in the subsequent cycles (2-week cycles). Treatment was continued until disease progression, unacceptable toxicity, withdrawal of consent or any other discontinuation criteria were met.	GCiC Plus Cixutumumab Gemcitabine: 1000 mg/m\^2 on Days 1 and 8 of each 3-week cycle for a total of 6 cycles (18 weeks). Cisplatin: 75 mg/m\^2 on Day 1 of each 3-week cycle for a total of 6 cycles (18 weeks). Cetuximab: Initial dose of 400 mg/m\^2 on Day 1 of Cycle 1 and subsequent doses of 250 mg/m\^2 Q1W of each 3-week cycle for a total of 6 cycles (18 weeks). Later administered at 500 mg/m\^2 Q2W in the subsequent cycles (2-week cycles). Cixutumumab: 6 mg/kg IV infusion Q1W on Days 1, 8, and 15 of each 3-week cycle for a total of 6 cycles (18 weeks). Later administered at 10 mg/kg IV Q2W in the subsequent cycles (2-week cycles). Treatment was continued until disease progression, unacceptable toxicity, withdrawal of consent or any other discontinuation criteria were met.
Overall Study Withdrawal by Subject	0	1	1	3
Overall Study Adverse Event	0	0	2	2

Baseline Characteristics

A Study of IMC-A12 (Cixutumumab) With and Without Other Standard Chemotherapies in Participants With Lung Cancer Who Have Not Received Chemotherapy Before

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Gemcitabine/Carboplatin/Cetuximab (GCC) n=4 Participants Gemcitabine: 1000 mg/m\^2 on Days 1 and 8 of each 3-week cycle for a total of 6 cycles (18 weeks). Cetuximab: Initial dose of 400 mg/m\^2 on Day 1 of Cycle 1, and subsequent doses of 250 mg/m\^2 Q1W of each 3-week cycle for a total of 6 cycles (18 weeks). Later administered at 500 mg/m\^2 Q2W in the subsequent cycles (2-week cycles). Carboplatin: AUC = 5 on Day 1 of each 3-week cycle for a total of 6 cycles (18 weeks). Treatment was continued until disease progression, unacceptable toxicity, withdrawal of consent or any other discontinuation criteria were met.	GCC Plus Cixutumumab n=6 Participants Gemcitabine: 1000 mg/m\^2 on Days 1 and 8 of each 3-week cycle for a total of 6 cycles (18 weeks). Cetuximab: Initial dose of 400 mg/m\^2 on Day 1 of Cycle 1, and subsequent doses of 250 mg/m\^2 Q1W of each 3-week cycle for a total of 6 cycles (18 weeks). Later administered at 500 mg/m\^2 Q2W in the subsequent cycles (2-week cycles). Carboplatin: AUC = 5 on Day 1 of each 3-week cycle for a total of 6 cycles (18 weeks). Cixutumumab: 6 mg/kg IV infusion Q1W on Days 1, 8, and 15 of each 3-week cycle for a total of 6 cycles (18 weeks). Later administered at 10 mg/kg IV Q2W in the subsequent cycles (2-week cycles). Treatment was continued until disease progression, unacceptable toxicity, withdrawal of consent or any other discontinuation criteria were met.	Gemcitabine/Cisplatin/Cetuximab (GCiC) n=29 Participants Gemcitabine: 1000 mg/m\^2 on Days 1 and 8 of each 3-week cycle for a total of 6 cycles (18 weeks). Cisplatin: 75 mg/m\^2 on Day 1 of each 3-week cycle for a total of 6 cycles (18 weeks). Cetuximab: Initial dose of 400 mg/m\^2 on Day 1 of Cycle 1, and subsequent doses of 250 mg/m\^2 Q1W of each 3-week cycle for a total of 6 cycles (18 weeks). Later administered at 500 mg/m\^2 Q2W in the subsequent cycles (2-week cycles). Treatment was continued until disease progression, unacceptable toxicity, withdrawal of consent or any other discontinuation criteria were met.	GCiC Plus Cixutumumab n=25 Participants Gemcitabine: 1000 mg/m\^2 on Days 1 and 8 of each 3-week cycle for a total of 6 cycles (18 weeks). Cisplatin: 75 mg/m\^2 on Day 1 of each 3-week cycle for a total of 6 cycles (18 weeks). Cetuximab: Initial dose of 400 mg/m\^2 on Day 1 of Cycle 1, and subsequent doses of 250 mg/m\^2 Q1W of each 3-week cycle for a total of 6 cycles (18 weeks). Later administered at 500 mg/m\^2 Q2W in the subsequent cycles (2-week cycle). Cixutumumab: 6 mg/kg IV infusion Q1W on Days 1, 8, and 15 of each 3-week cycle for a total of 6 cycles (18 weeks). Later administered at 10 mg/kg IV Q2W in the subsequent cycles (2-week cycles). Treatment was continued until disease progression, unacceptable toxicity, withdrawal of consent or any other discontinuation criteria were met.	Total n=64 Participants Total of all reporting groups
Age, Continuous	68.50 years n=5 Participants	54.50 years n=7 Participants	64.00 years n=5 Participants	60.00 years n=4 Participants	62.00 years n=21 Participants
Sex: Female, Male Female	1 Participants n=5 Participants	2 Participants n=7 Participants	13 Participants n=5 Participants	11 Participants n=4 Participants	27 Participants n=21 Participants
Sex: Female, Male Male	3 Participants n=5 Participants	4 Participants n=7 Participants	16 Participants n=5 Participants	14 Participants n=4 Participants	37 Participants n=21 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	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
Ethnicity (NIH/OMB) Not Hispanic or Latino	4 Participants n=5 Participants	6 Participants n=7 Participants	29 Participants n=5 Participants	24 Participants n=4 Participants	63 Participants n=21 Participants
Ethnicity (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
Race/Ethnicity, Customized White	4 Participants n=5 Participants	6 Participants n=7 Participants	26 Participants n=5 Participants	22 Participants n=4 Participants	58 Participants n=21 Participants
Race/Ethnicity, Customized Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	3 Participants n=5 Participants	3 Participants n=4 Participants	6 Participants n=21 Participants
Region of Enrollment United States	4 Participants n=5 Participants	6 Participants n=7 Participants	29 Participants n=5 Participants	25 Participants n=4 Participants	64 Participants n=21 Participants
Height	173.10 centimeters (cm) STANDARD_DEVIATION 3.982 • n=5 Participants	176.78 centimeters (cm) STANDARD_DEVIATION 8.935 • n=7 Participants	170.04 centimeters (cm) STANDARD_DEVIATION 9.356 • n=5 Participants	167.79 centimeters (cm) STANDARD_DEVIATION 10.537 • n=4 Participants	169.99 centimeters (cm) STANDARD_DEVIATION 9.758 • n=21 Participants
Weight	74.93 kilograms (kg) STANDARD_DEVIATION 13.814 • n=5 Participants	80.43 kilograms (kg) STANDARD_DEVIATION 16.720 • n=7 Participants	76.30 kilograms (kg) STANDARD_DEVIATION 13.908 • n=5 Participants	72.90 kilograms (kg) STANDARD_DEVIATION 15.957 • n=4 Participants	75.27 kilograms (kg) STANDARD_DEVIATION 14.815 • n=21 Participants
Body Surface Area (BSA)	1.89 square meters (m^2) STANDARD_DEVIATION 0.186 • n=5 Participants	1.98 square meters (m^2) STANDARD_DEVIATION 0.223 • n=7 Participants	1.89 square meters (m^2) STANDARD_DEVIATION 0.214 • n=5 Participants	1.84 square meters (m^2) STANDARD_DEVIATION 0.246 • n=4 Participants	1.88 square meters (m^2) STANDARD_DEVIATION 0.225 • n=21 Participants
Eastern Cooperative Oncology Status Performance Status (ECOG PS) Score 0 = Fully Active	0 Participants n=5 Participants	4 Participants n=7 Participants	5 Participants n=5 Participants	9 Participants n=4 Participants	18 Participants n=21 Participants
Eastern Cooperative Oncology Status Performance Status (ECOG PS) Score 1 = Ambulatory, Restricted Work Activity	4 Participants n=5 Participants	2 Participants n=7 Participants	24 Participants n=5 Participants	16 Participants n=4 Participants	46 Participants n=21 Participants
Randomization Stratum Squamous	2 Participants n=5 Participants	3 Participants n=7 Participants	14 Participants n=5 Participants	11 Participants n=4 Participants	30 Participants n=21 Participants
Randomization Stratum Nonsquamous	2 Participants n=5 Participants	3 Participants n=7 Participants	15 Participants n=5 Participants	14 Participants n=4 Participants	34 Participants n=21 Participants

PRIMARY outcome

Timeframe: Randomization to measured progressive disease (PD) (up to 16.9 months)

Population: All participants randomized to GCiC and GCiC Plus Cixutumumab arms. Efficacy data were not summarized for the original treatment arms (GCC and GCC Plus Cixutumumab) since such summaries were not considered relevant to the study objectives under the amended protocol.

Outcome measures

Outcome measures
Measure	Gemcitabine/Cisplatin/Cetuximab (GCiC) n=29 Participants Gemcitabine: 1000 mg/m\^2 on Days 1 and 8 of each 3-week cycle for a total of 6 cycles (18 weeks). Cisplatin: 75 mg/m\^2 on Day 1 of each 3-week cycle for a total of 6 cycles (18 weeks). Cetuximab: Initial dose of 400 mg/m\^2 on Day 1 of Cycle 1, and subsequent doses of 250 mg/m\^2 Q1W of each 3-week cycle for a total of 6 cycles (18 weeks). Later administered at 500 mg/m\^2 Q2W in the subsequent cycles (2-week cycles). Treatment was continued until disease progression, unacceptable toxicity, withdrawal of consent or any other discontinuation criteria were met.	GCiC Plus Cixutumumab n=25 Participants Gemcitabine: 1000 mg/m\^2 on Days 1 and 8 of each 3-week cycle for a total of 6 cycles (18 weeks). Cisplatin: 75 mg/m\^2 on Day 1 of each 3-week cycle for a total of 6 cycles (18 weeks). Cetuximab: Initial dose of 400 mg/m\^2 on Day 1 of Cycle 1, and subsequent doses of 250 mg/m\^2 Q1W of each 3-week cycle for a total of 6 cycles (18 weeks). Later administered at 500 mg/m\^2 Q2W in the subsequent cycles (2-week cycles). Cixutumumab: 6 mg/kg IV infusion Q1W on Days 1, 8, and 15 of each 3-week cycle for a total of 6 cycles (18 weeks). Later administered at 10 mg/kg IV Q2W in the subsequent cycles (2-week cycles). Treatment was continued until disease progression, unacceptable toxicity, withdrawal of consent or any other discontinuation criteria were met.	Gemcitabine/Cisplatin/Cetuximab (GCiC) Gemcitabine: 1000 mg/m\^2 on Days 1 and 8 of each 3-week cycle for a total of 6 cycles (18 weeks). Cisplatin: 75 mg/m\^2 on Day 1 of each 3-week cycle for a total of 6 cycles (18 weeks). Cetuximab: Initial dose of 400 mg/m\^2 on Day 1 of Cycle 1, and subsequent doses of 250 mg/m\^2 Q1W of each 3-week cycle for a total of 6 cycles (18 weeks). Later administered at 500 mg/m\^2 Q2W in the subsequent cycles (2-week cycles). Treatment was continued until disease progression, unacceptable toxicity, withdrawal of consent or any other discontinuation criteria were met.	GCiC Plus Cixutumumab Gemcitabine: 1000 mg/m\^2 on Days 1 and 8 of each 3-week cycle for a total of 6 cycles (18 weeks). Cisplatin: 75 mg/m\^2 on Day 1 of each 3-week cycle for a total of 6 cycles (18 weeks). Cetuximab: Initial dose of 400 mg/m\^2 on Day 1 of Cycle 1, and subsequent doses of 250 mg/m\^2 Q1W of each 3-week cycle for a total of 6 cycles (18 weeks). Later administered at 500 mg/m\^2 Q2W in the subsequent cycles (2-week cycles). Cixutumumab: 6 mg/kg IV infusion Q1W on Days 1, 8, and 15 of each 3-week cycle for a total of 6 cycles (18 weeks). Later administered at 10 mg/kg IV Q2W in the subsequent cycles (2-week cycles). Treatment was continued until disease progression, unacceptable toxicity, withdrawal of consent or any other discontinuation criteria were met.
Percentage of Participants With Complete Response (CR) or Partial Response (PR) [Objective Response Rate (ORR)]	31.0 percentage of participants Interval 14.2 to 47.9	20.0 percentage of participants Interval 4.3 to 35.7	—	—

SECONDARY outcome

Timeframe: Randomization to death due to any cause or censor (up to 30.4 months)

Population: All participants randomized to GCiC and GCiC Plus Cixutumumab arms. Participants censored: GCiC = 6, GCiC Plus cixutumumab = 6. Efficacy data were not summarized for the original treatment arms (GCC and GCC Plus Cixutumumab) since such summaries were not considered relevant to the study objectives under the amended protocol.

OS was defined as the duration from the date of randomization to the date of death from any cause. For participants who were alive, OS was censored at the date of last follow-up visit or at the date of last contact.

Outcome measures

Outcome measures
Measure	Gemcitabine/Cisplatin/Cetuximab (GCiC) n=29 Participants Gemcitabine: 1000 mg/m\^2 on Days 1 and 8 of each 3-week cycle for a total of 6 cycles (18 weeks). Cisplatin: 75 mg/m\^2 on Day 1 of each 3-week cycle for a total of 6 cycles (18 weeks). Cetuximab: Initial dose of 400 mg/m\^2 on Day 1 of Cycle 1, and subsequent doses of 250 mg/m\^2 Q1W of each 3-week cycle for a total of 6 cycles (18 weeks). Later administered at 500 mg/m\^2 Q2W in the subsequent cycles (2-week cycles). Treatment was continued until disease progression, unacceptable toxicity, withdrawal of consent or any other discontinuation criteria were met.	GCiC Plus Cixutumumab n=25 Participants Gemcitabine: 1000 mg/m\^2 on Days 1 and 8 of each 3-week cycle for a total of 6 cycles (18 weeks). Cisplatin: 75 mg/m\^2 on Day 1 of each 3-week cycle for a total of 6 cycles (18 weeks). Cetuximab: Initial dose of 400 mg/m\^2 on Day 1 of Cycle 1, and subsequent doses of 250 mg/m\^2 Q1W of each 3-week cycle for a total of 6 cycles (18 weeks). Later administered at 500 mg/m\^2 Q2W in the subsequent cycles (2-week cycles). Cixutumumab: 6 mg/kg IV infusion Q1W on Days 1, 8, and 15 of each 3-week cycle for a total of 6 cycles (18 weeks). Later administered at 10 mg/kg IV Q2W in the subsequent cycles (2-week cycles). Treatment was continued until disease progression, unacceptable toxicity, withdrawal of consent or any other discontinuation criteria were met.	Gemcitabine/Cisplatin/Cetuximab (GCiC) Gemcitabine: 1000 mg/m\^2 on Days 1 and 8 of each 3-week cycle for a total of 6 cycles (18 weeks). Cisplatin: 75 mg/m\^2 on Day 1 of each 3-week cycle for a total of 6 cycles (18 weeks). Cetuximab: Initial dose of 400 mg/m\^2 on Day 1 of Cycle 1, and subsequent doses of 250 mg/m\^2 Q1W of each 3-week cycle for a total of 6 cycles (18 weeks). Later administered at 500 mg/m\^2 Q2W in the subsequent cycles (2-week cycles). Treatment was continued until disease progression, unacceptable toxicity, withdrawal of consent or any other discontinuation criteria were met.	GCiC Plus Cixutumumab Gemcitabine: 1000 mg/m\^2 on Days 1 and 8 of each 3-week cycle for a total of 6 cycles (18 weeks). Cisplatin: 75 mg/m\^2 on Day 1 of each 3-week cycle for a total of 6 cycles (18 weeks). Cetuximab: Initial dose of 400 mg/m\^2 on Day 1 of Cycle 1, and subsequent doses of 250 mg/m\^2 Q1W of each 3-week cycle for a total of 6 cycles (18 weeks). Later administered at 500 mg/m\^2 Q2W in the subsequent cycles (2-week cycles). Cixutumumab: 6 mg/kg IV infusion Q1W on Days 1, 8, and 15 of each 3-week cycle for a total of 6 cycles (18 weeks). Later administered at 10 mg/kg IV Q2W in the subsequent cycles (2-week cycles). Treatment was continued until disease progression, unacceptable toxicity, withdrawal of consent or any other discontinuation criteria were met.
Overall Survival (OS)	11.5 months Interval 5.3 to 14.8	8.9 months Interval 7.0 to 13.2	—	—

SECONDARY outcome

Timeframe: Randomization to PD or death due to any cause or censor (up to 16.9 months)

Population: All participants randomized to GCiC and GCiC Plus Cixutumumab arms. Participants censored: GCiC = 2, GCiC Plus cixutumumab = 10. Efficacy data were not summarized for the original treatment arms (GCC and GCC Plus Cixutumumab) since such summaries were not considered relevant to the study objectives under the amended protocol.

PFS was defined as the duration from the date of randomization until disease progression or death due to any cause, whichever occurred first. Response was defined using RECIST, v 1.0 criteria. PD was defined as having a ≥20% increase in sum of LD of target lesions or the appearance of new lesions and/or unequivocal progression of non-target lesions. For participants who were alive and without disease progression, PFS was censored at the date of last objective tumor assessment. For participants who did not experience disease progression and were lost to follow-up, PFS was censored at the date of the last objective tumor assessment or the date of last contact.

Outcome measures

Outcome measures
Measure	Gemcitabine/Cisplatin/Cetuximab (GCiC) n=29 Participants Gemcitabine: 1000 mg/m\^2 on Days 1 and 8 of each 3-week cycle for a total of 6 cycles (18 weeks). Cisplatin: 75 mg/m\^2 on Day 1 of each 3-week cycle for a total of 6 cycles (18 weeks). Cetuximab: Initial dose of 400 mg/m\^2 on Day 1 of Cycle 1, and subsequent doses of 250 mg/m\^2 Q1W of each 3-week cycle for a total of 6 cycles (18 weeks). Later administered at 500 mg/m\^2 Q2W in the subsequent cycles (2-week cycles). Treatment was continued until disease progression, unacceptable toxicity, withdrawal of consent or any other discontinuation criteria were met.	GCiC Plus Cixutumumab n=25 Participants Gemcitabine: 1000 mg/m\^2 on Days 1 and 8 of each 3-week cycle for a total of 6 cycles (18 weeks). Cisplatin: 75 mg/m\^2 on Day 1 of each 3-week cycle for a total of 6 cycles (18 weeks). Cetuximab: Initial dose of 400 mg/m\^2 on Day 1 of Cycle 1, and subsequent doses of 250 mg/m\^2 Q1W of each 3-week cycle for a total of 6 cycles (18 weeks). Later administered at 500 mg/m\^2 Q2W in the subsequent cycles (2-week cycles). Cixutumumab: 6 mg/kg IV infusion Q1W on Days 1, 8, and 15 of each 3-week cycle for a total of 6 cycles (18 weeks). Later administered at 10 mg/kg IV Q2W in the subsequent cycles (2-week cycles). Treatment was continued until disease progression, unacceptable toxicity, withdrawal of consent or any other discontinuation criteria were met.	Gemcitabine/Cisplatin/Cetuximab (GCiC) Gemcitabine: 1000 mg/m\^2 on Days 1 and 8 of each 3-week cycle for a total of 6 cycles (18 weeks). Cisplatin: 75 mg/m\^2 on Day 1 of each 3-week cycle for a total of 6 cycles (18 weeks). Cetuximab: Initial dose of 400 mg/m\^2 on Day 1 of Cycle 1, and subsequent doses of 250 mg/m\^2 Q1W of each 3-week cycle for a total of 6 cycles (18 weeks). Later administered at 500 mg/m\^2 Q2W in the subsequent cycles (2-week cycles). Treatment was continued until disease progression, unacceptable toxicity, withdrawal of consent or any other discontinuation criteria were met.	GCiC Plus Cixutumumab Gemcitabine: 1000 mg/m\^2 on Days 1 and 8 of each 3-week cycle for a total of 6 cycles (18 weeks). Cisplatin: 75 mg/m\^2 on Day 1 of each 3-week cycle for a total of 6 cycles (18 weeks). Cetuximab: Initial dose of 400 mg/m\^2 on Day 1 of Cycle 1, and subsequent doses of 250 mg/m\^2 Q1W of each 3-week cycle for a total of 6 cycles (18 weeks). Later administered at 500 mg/m\^2 Q2W in the subsequent cycles (2-week cycles). Cixutumumab: 6 mg/kg IV infusion Q1W on Days 1, 8, and 15 of each 3-week cycle for a total of 6 cycles (18 weeks). Later administered at 10 mg/kg IV Q2W in the subsequent cycles (2-week cycles). Treatment was continued until disease progression, unacceptable toxicity, withdrawal of consent or any other discontinuation criteria were met.
Progression-Free Survival (PFS)	4.2 months Interval 2.9 to 6.2	5.6 months Interval 2.6 to 7.0	—	—

SECONDARY outcome

Timeframe: Randomization to months until PD or censor (up to 16.9 months)

Population: All participants (pts) randomized to GCiC and GCiC Plus Cixutumumab arms. Participants censored: GCiC = 9, GCiC Plus Cixutumumab = 12. Efficacy data were not summarized for the original treatment arms (GCC and GCC Plus Cixutumumab) since such summaries were not considered relevant to the study objectives under the amended protocol.

TTP was defined as the duration from the date of randomization until the date of disease progression. Response was defined using RECIST v 1.0 criteria. PD was defined as having a ≥20% increase in the sum of LD of target lesions or the appearance of new lesions and/or unequivocal progression of non-target lesions. For participants without disease progression, TTP was censored at the date of last objective tumor assessment. For participants without disease progression and were subsequently lost to follow-up, TTP was censored at the date of last follow-up visit or at the date of last contact.

Outcome measures

Outcome measures
Measure	Gemcitabine/Cisplatin/Cetuximab (GCiC) n=29 Participants Gemcitabine: 1000 mg/m\^2 on Days 1 and 8 of each 3-week cycle for a total of 6 cycles (18 weeks). Cisplatin: 75 mg/m\^2 on Day 1 of each 3-week cycle for a total of 6 cycles (18 weeks). Cetuximab: Initial dose of 400 mg/m\^2 on Day 1 of Cycle 1, and subsequent doses of 250 mg/m\^2 Q1W of each 3-week cycle for a total of 6 cycles (18 weeks). Later administered at 500 mg/m\^2 Q2W in the subsequent cycles (2-week cycles). Treatment was continued until disease progression, unacceptable toxicity, withdrawal of consent or any other discontinuation criteria were met.	GCiC Plus Cixutumumab n=25 Participants Gemcitabine: 1000 mg/m\^2 on Days 1 and 8 of each 3-week cycle for a total of 6 cycles (18 weeks). Cisplatin: 75 mg/m\^2 on Day 1 of each 3-week cycle for a total of 6 cycles (18 weeks). Cetuximab: Initial dose of 400 mg/m\^2 on Day 1 of Cycle 1, and subsequent doses of 250 mg/m\^2 Q1W of each 3-week cycle for a total of 6 cycles (18 weeks). Later administered at 500 mg/m\^2 Q2W in the subsequent cycles (2-week cycles). Cixutumumab: 6 mg/kg IV infusion Q1W on Days 1, 8, and 15 of each 3-week cycle for a total of 6 cycles (18 weeks). Later administered at 10 mg/kg IV Q2W in the subsequent cycles (2-week cycles). Treatment was continued until disease progression, unacceptable toxicity, withdrawal of consent or any other discontinuation criteria were met.	Gemcitabine/Cisplatin/Cetuximab (GCiC) Gemcitabine: 1000 mg/m\^2 on Days 1 and 8 of each 3-week cycle for a total of 6 cycles (18 weeks). Cisplatin: 75 mg/m\^2 on Day 1 of each 3-week cycle for a total of 6 cycles (18 weeks). Cetuximab: Initial dose of 400 mg/m\^2 on Day 1 of Cycle 1, and subsequent doses of 250 mg/m\^2 Q1W of each 3-week cycle for a total of 6 cycles (18 weeks). Later administered at 500 mg/m\^2 Q2W in the subsequent cycles (2-week cycles). Treatment was continued until disease progression, unacceptable toxicity, withdrawal of consent or any other discontinuation criteria were met.	GCiC Plus Cixutumumab Gemcitabine: 1000 mg/m\^2 on Days 1 and 8 of each 3-week cycle for a total of 6 cycles (18 weeks). Cisplatin: 75 mg/m\^2 on Day 1 of each 3-week cycle for a total of 6 cycles (18 weeks). Cetuximab: Initial dose of 400 mg/m\^2 on Day 1 of Cycle 1, and subsequent doses of 250 mg/m\^2 Q1W of each 3-week cycle for a total of 6 cycles (18 weeks). Later administered at 500 mg/m\^2 Q2W in the subsequent cycles (2-week cycles). Cixutumumab: 6 mg/kg IV infusion Q1W on Days 1, 8, and 15 of each 3-week cycle for a total of 6 cycles (18 weeks). Later administered at 10 mg/kg IV Q2W in the subsequent cycles (2-week cycles). Treatment was continued until disease progression, unacceptable toxicity, withdrawal of consent or any other discontinuation criteria were met.
Time To Progression (TTP)	5.8 months Interval 3.9 to 6.7	5.7 months Interval 2.7 to 11.7	—	—

SECONDARY outcome

Timeframe: Date of first response to the date of PD or death due to any cause or censor ( up to 15.5 months)

Population: All pts randomized to GCiC and GCiC Plus Cixutumumab arms and who had CR or PR, except 1 pt in GCiC group eliminated d/t PR after starting additional treatment. Participants censored: GCiC = 0, GCiC Plus Cixutumumab = 1. Efficacy data were not summarized for the original treatment arms (GCC and GCC Plus Cixutumumab) due to the amended protocol.

The duration of CR or PR was defined as the time from first objective status assessment of CR or PR to the first time of disease progression or death. Response was defined using RECIST v 1.0 criteria. CR was defined as the disappearance of all target lesions and non-target lesions. PR was defined as having at least a 30% decrease in sum of LD of target lesions. Duration of response was censored on the date of last tumor assessment for participants who were alive and have no evidence of disease progression.

Outcome measures

Outcome measures
Measure	Gemcitabine/Cisplatin/Cetuximab (GCiC) n=8 Participants Gemcitabine: 1000 mg/m\^2 on Days 1 and 8 of each 3-week cycle for a total of 6 cycles (18 weeks). Cisplatin: 75 mg/m\^2 on Day 1 of each 3-week cycle for a total of 6 cycles (18 weeks). Cetuximab: Initial dose of 400 mg/m\^2 on Day 1 of Cycle 1, and subsequent doses of 250 mg/m\^2 Q1W of each 3-week cycle for a total of 6 cycles (18 weeks). Later administered at 500 mg/m\^2 Q2W in the subsequent cycles (2-week cycles). Treatment was continued until disease progression, unacceptable toxicity, withdrawal of consent or any other discontinuation criteria were met.	GCiC Plus Cixutumumab n=4 Participants Gemcitabine: 1000 mg/m\^2 on Days 1 and 8 of each 3-week cycle for a total of 6 cycles (18 weeks). Cisplatin: 75 mg/m\^2 on Day 1 of each 3-week cycle for a total of 6 cycles (18 weeks). Cetuximab: Initial dose of 400 mg/m\^2 on Day 1 of Cycle 1, and subsequent doses of 250 mg/m\^2 Q1W of each 3-week cycle for a total of 6 cycles (18 weeks). Later administered at 500 mg/m\^2 Q2W in the subsequent cycles (2-week cycles). Cixutumumab: 6 mg/kg IV infusion Q1W on Days 1, 8, and 15 of each 3-week cycle for a total of 6 cycles (18 weeks). Later administered at 10 mg/kg IV Q2W in the subsequent cycles (2-week cycles). Treatment was continued until disease progression, unacceptable toxicity, withdrawal of consent or any other discontinuation criteria were met.	Gemcitabine/Cisplatin/Cetuximab (GCiC) Gemcitabine: 1000 mg/m\^2 on Days 1 and 8 of each 3-week cycle for a total of 6 cycles (18 weeks). Cisplatin: 75 mg/m\^2 on Day 1 of each 3-week cycle for a total of 6 cycles (18 weeks). Cetuximab: Initial dose of 400 mg/m\^2 on Day 1 of Cycle 1, and subsequent doses of 250 mg/m\^2 Q1W of each 3-week cycle for a total of 6 cycles (18 weeks). Later administered at 500 mg/m\^2 Q2W in the subsequent cycles (2-week cycles). Treatment was continued until disease progression, unacceptable toxicity, withdrawal of consent or any other discontinuation criteria were met.	GCiC Plus Cixutumumab Gemcitabine: 1000 mg/m\^2 on Days 1 and 8 of each 3-week cycle for a total of 6 cycles (18 weeks). Cisplatin: 75 mg/m\^2 on Day 1 of each 3-week cycle for a total of 6 cycles (18 weeks). Cetuximab: Initial dose of 400 mg/m\^2 on Day 1 of Cycle 1, and subsequent doses of 250 mg/m\^2 Q1W of each 3-week cycle for a total of 6 cycles (18 weeks). Later administered at 500 mg/m\^2 Q2W in the subsequent cycles (2-week cycles). Cixutumumab: 6 mg/kg IV infusion Q1W on Days 1, 8, and 15 of each 3-week cycle for a total of 6 cycles (18 weeks). Later administered at 10 mg/kg IV Q2W in the subsequent cycles (2-week cycles). Treatment was continued until disease progression, unacceptable toxicity, withdrawal of consent or any other discontinuation criteria were met.
Duration of Response	4.8 months Interval 4.2 to 5.3	4.8 months Interval 2.9 to 15.5	—	—

SECONDARY outcome

Timeframe: Randomization to last dose of study medication (up to 11.7 months) plus 30-day safety follow-up

Population: All randomized participants.

Data presented are the number of participants who experienced 1 or more AEs, serious AEs (SAEs), and AEs that lead to death during the study including the 30-day follow-up. A summary of SAEs and other non-serious AEs, regardless of causality is located in the Reported Adverse Events section of this report.

Outcome measures

Outcome measures
Measure	Gemcitabine/Cisplatin/Cetuximab (GCiC) n=4 Participants Gemcitabine: 1000 mg/m\^2 on Days 1 and 8 of each 3-week cycle for a total of 6 cycles (18 weeks). Cisplatin: 75 mg/m\^2 on Day 1 of each 3-week cycle for a total of 6 cycles (18 weeks). Cetuximab: Initial dose of 400 mg/m\^2 on Day 1 of Cycle 1, and subsequent doses of 250 mg/m\^2 Q1W of each 3-week cycle for a total of 6 cycles (18 weeks). Later administered at 500 mg/m\^2 Q2W in the subsequent cycles (2-week cycles). Treatment was continued until disease progression, unacceptable toxicity, withdrawal of consent or any other discontinuation criteria were met.	GCiC Plus Cixutumumab n=6 Participants Gemcitabine: 1000 mg/m\^2 on Days 1 and 8 of each 3-week cycle for a total of 6 cycles (18 weeks). Cisplatin: 75 mg/m\^2 on Day 1 of each 3-week cycle for a total of 6 cycles (18 weeks). Cetuximab: Initial dose of 400 mg/m\^2 on Day 1 of Cycle 1, and subsequent doses of 250 mg/m\^2 Q1W of each 3-week cycle for a total of 6 cycles (18 weeks). Later administered at 500 mg/m\^2 Q2W in the subsequent cycles (2-week cycles). Cixutumumab: 6 mg/kg IV infusion Q1W on Days 1, 8, and 15 of each 3-week cycle for a total of 6 cycles (18 weeks). Later administered at 10 mg/kg IV Q2W in the subsequent cycles (2-week cycles). Treatment was continued until disease progression, unacceptable toxicity, withdrawal of consent or any other discontinuation criteria were met.	Gemcitabine/Cisplatin/Cetuximab (GCiC) n=29 Participants Gemcitabine: 1000 mg/m\^2 on Days 1 and 8 of each 3-week cycle for a total of 6 cycles (18 weeks). Cisplatin: 75 mg/m\^2 on Day 1 of each 3-week cycle for a total of 6 cycles (18 weeks). Cetuximab: Initial dose of 400 mg/m\^2 on Day 1 of Cycle 1, and subsequent doses of 250 mg/m\^2 Q1W of each 3-week cycle for a total of 6 cycles (18 weeks). Later administered at 500 mg/m\^2 Q2W in the subsequent cycles (2-week cycles). Treatment was continued until disease progression, unacceptable toxicity, withdrawal of consent or any other discontinuation criteria were met.	GCiC Plus Cixutumumab n=25 Participants Gemcitabine: 1000 mg/m\^2 on Days 1 and 8 of each 3-week cycle for a total of 6 cycles (18 weeks). Cisplatin: 75 mg/m\^2 on Day 1 of each 3-week cycle for a total of 6 cycles (18 weeks). Cetuximab: Initial dose of 400 mg/m\^2 on Day 1 of Cycle 1, and subsequent doses of 250 mg/m\^2 Q1W of each 3-week cycle for a total of 6 cycles (18 weeks). Later administered at 500 mg/m\^2 Q2W in the subsequent cycles (2-week cycles). Cixutumumab: 6 mg/kg IV infusion Q1W on Days 1, 8, and 15 of each 3-week cycle for a total of 6 cycles (18 weeks). Later administered at 10 mg/kg IV Q2W in the subsequent cycles (2-week cycles). Treatment was continued until disease progression, unacceptable toxicity, withdrawal of consent or any other discontinuation criteria were met.
Number of Participants With Adverse Events (AEs) or Deaths AEs	4 Participants	6 Participants	29 Participants	25 Participants
Number of Participants With Adverse Events (AEs) or Deaths SAEs	4 Participants	5 Participants	20 Participants	15 Participants
Number of Participants With Adverse Events (AEs) or Deaths Deaths Due to AEs	1 Participants	1 Participants	4 Participants	1 Participants

Adverse Events

Gemcitabine/Carboplatin/Cetuximab (GCC)

Serious events: 4 serious events

Other events: 4 other events

Deaths: 0 deaths

GCC Plus Cixutumumab

Serious events: 5 serious events

Other events: 6 other events

Deaths: 0 deaths

Gemcitabine/Cisplatin/Cetuximab (GCiC)

Serious events: 20 serious events

Other events: 29 other events

Deaths: 0 deaths

GCiC Plus Cixutumumab

Serious events: 15 serious events

Other events: 25 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Gemcitabine/Carboplatin/Cetuximab (GCC) n=4 participants at risk Gemcitabine: 1000 mg/m\^2 on Days 1 and 8 of each 3-week cycle for a total of 6 cycles (18 weeks). Cetuximab: Initial dose of 400 mg/m\^2 on Day 1 of Cycle 1, and subsequent doses of 250 mg/m\^2 Q1W of each 3-week cycle for a total of 6 cycles (18 weeks). Later administered at 500 mg/m\^2 Q2W in the subsequent cycles (2-week cycles). Carboplatin: AUC = 5 on Day 1 of each 3-week cycle for a total of 6 cycles (18 weeks). Treatment was continued until disease progression, unacceptable toxicity, withdrawal of consent or any other discontinuation criteria were met.	GCC Plus Cixutumumab n=6 participants at risk Gemcitabine: 1000 mg/m\^2 on Days 1 and 8 of each 3-week cycle for a total of 6 cycles (18 weeks). Cetuximab: Initial dose of 400 mg/m\^2 on Day 1 of Cycle 1, and subsequent doses of 250 mg/m\^2 Q1W of each 3-week cycle for a total of 6 cycles (18 weeks). Later administered at 500 mg/m\^2 Q2W in the subsequent cycles (2-week cycles). Carboplatin: AUC = 5 on Day 1 of each 3-week cycle for a total of 6 cycles (18 weeks). Cixutumumab: 6 mg/kg IV infusion Q1W on Days 1, 8, and 15 of each 3-week cycle for a total of 6 cycles (18 weeks). Later administered at 10 mg/kg IV Q2W in the subsequent cycles (2-week cycles). Treatment was continued until disease progression, unacceptable toxicity, withdrawal of consent or any other discontinuation criteria were met.	Gemcitabine/Cisplatin/Cetuximab (GCiC) n=29 participants at risk Gemcitabine: 1000 mg/m\^2 on Days 1 and 8 of each 3-week cycle for a total of 6 cycles (18 weeks). Cisplatin: 75 mg/m\^2 on Day 1 of each 3-week cycle for a total of 6 cycles (18 weeks). Cetuximab: Initial dose of 400 mg/m\^2 on Day 1 of Cycle 1, and subsequent doses of 250 mg/m\^2 Q1W of each 3-week cycle for a total of 6 cycles (18 weeks). Later administered at 500 mg/m\^2 Q2W in the subsequent cycles (2-week cycles). Treatment was continued until disease progression, unacceptable toxicity, withdrawal of consent or any other discontinuation criteria were met.	GCiC Plus Cixutumumab n=25 participants at risk Gemcitabine: 1000 mg/m\^2 on Days 1 and 8 of each 3-week cycle for a total of 6 cycles (18 weeks). Cisplatin: 75 mg/m\^2 on Day 1 of each 3-week cycle for a total of 6 cycles (18 weeks). Cetuximab: Initial dose of 400 mg/m\^2 on Day 1 of Cycle 1, and subsequent doses of 250 mg/m\^2 Q1W of each 3-week cycle for a total of 6 cycles (18 weeks). Later administered at 500 mg/m\^2 Q2W in the subsequent cycles (2-week cycles). Cixutumumab: 6 mg/kg IV infusion Q1W on Days 1, 8, and 15 of each 3-week cycle for a total of 6 cycles (18 weeks). Later administered at 10 mg/kg IV Q2W in the subsequent cycles (2-week cycles). Treatment was continued until disease progression, unacceptable toxicity, withdrawal of consent or any other discontinuation criteria were met.
Respiratory, thoracic and mediastinal disorders Pneumothorax	0.00% 0/4	0.00% 0/6	3.4% 1/29 • Number of events 1	0.00% 0/25
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	25.0% 1/4 • Number of events 1	0.00% 0/6	6.9% 2/29 • Number of events 2	0.00% 0/25
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.00% 0/4	0.00% 0/6	3.4% 1/29 • Number of events 1	0.00% 0/25
Vascular disorders Deep vein thrombosis	0.00% 0/4	0.00% 0/6	6.9% 2/29 • Number of events 2	0.00% 0/25
Vascular disorders Hypotension	0.00% 0/4	0.00% 0/6	3.4% 1/29 • Number of events 2	0.00% 0/25
Vascular disorders Orthostatic hypotension	0.00% 0/4	0.00% 0/6	0.00% 0/29	4.0% 1/25 • Number of events 1
Blood and lymphatic system disorders Anaemia	0.00% 0/4	0.00% 0/6	3.4% 1/29 • Number of events 1	0.00% 0/25
Blood and lymphatic system disorders Leukopenia	0.00% 0/4	0.00% 0/6	3.4% 1/29 • Number of events 1	0.00% 0/25
Blood and lymphatic system disorders Neutropenia	0.00% 0/4	0.00% 0/6	10.3% 3/29 • Number of events 3	0.00% 0/25
Blood and lymphatic system disorders Thrombocytopenia	100.0% 4/4 • Number of events 6	66.7% 4/6 • Number of events 5	6.9% 2/29 • Number of events 2	4.0% 1/25 • Number of events 1
Cardiac disorders Acute myocardial infarction	0.00% 0/4	0.00% 0/6	3.4% 1/29 • Number of events 1	0.00% 0/25
Cardiac disorders Atrial flutter	0.00% 0/4	0.00% 0/6	3.4% 1/29 • Number of events 1	0.00% 0/25
Cardiac disorders Cardiopulmonary failure	0.00% 0/4	0.00% 0/6	3.4% 1/29 • Number of events 1	0.00% 0/25
Cardiac disorders Intracardiac thrombus	0.00% 0/4	0.00% 0/6	0.00% 0/29	4.0% 1/25 • Number of events 1
Gastrointestinal disorders Abdominal pain	0.00% 0/4	0.00% 0/6	3.4% 1/29 • Number of events 1	0.00% 0/25
Gastrointestinal disorders Diarrhoea	0.00% 0/4	0.00% 0/6	0.00% 0/29	4.0% 1/25 • Number of events 1
Gastrointestinal disorders Gastrointestinal haemorrhage	0.00% 0/4	0.00% 0/6	0.00% 0/29	4.0% 1/25 • Number of events 1
Gastrointestinal disorders Glossodynia	0.00% 0/4	0.00% 0/6	0.00% 0/29	4.0% 1/25 • Number of events 1
Gastrointestinal disorders Pancreatitis	0.00% 0/4	0.00% 0/6	0.00% 0/29	4.0% 1/25 • Number of events 1
Gastrointestinal disorders Pneumatosis intestinalis	0.00% 0/4	0.00% 0/6	0.00% 0/29	4.0% 1/25 • Number of events 1
Gastrointestinal disorders Stomatitis	0.00% 0/4	16.7% 1/6 • Number of events 1	0.00% 0/29	0.00% 0/25
Gastrointestinal disorders Vomiting	0.00% 0/4	0.00% 0/6	0.00% 0/29	4.0% 1/25 • Number of events 1
General disorders Disease progression	25.0% 1/4 • Number of events 1	0.00% 0/6	0.00% 0/29	4.0% 1/25 • Number of events 1
General disorders Infusion related reaction	0.00% 0/4	16.7% 1/6 • Number of events 1	0.00% 0/29	4.0% 1/25 • Number of events 1
General disorders Non-cardiac chest pain	0.00% 0/4	0.00% 0/6	3.4% 1/29 • Number of events 1	0.00% 0/25
General disorders Oedema	0.00% 0/4	0.00% 0/6	0.00% 0/29	4.0% 1/25 • Number of events 1
General disorders Pyrexia	0.00% 0/4	0.00% 0/6	3.4% 1/29 • Number of events 1	0.00% 0/25
General disorders Sudden death	0.00% 0/4	16.7% 1/6 • Number of events 1	0.00% 0/29	0.00% 0/25
Hepatobiliary disorders Gallbladder non-functioning	0.00% 0/4	0.00% 0/6	3.4% 1/29 • Number of events 1	0.00% 0/25
Infections and infestations Cellulitis	0.00% 0/4	0.00% 0/6	3.4% 1/29 • Number of events 1	0.00% 0/25
Infections and infestations Lobar pneumonia	0.00% 0/4	0.00% 0/6	3.4% 1/29 • Number of events 1	0.00% 0/25
Infections and infestations Pneumonia	0.00% 0/4	0.00% 0/6	6.9% 2/29 • Number of events 2	4.0% 1/25 • Number of events 1
Infections and infestations Sepsis	0.00% 0/4	0.00% 0/6	0.00% 0/29	4.0% 1/25 • Number of events 1
Infections and infestations Wound infection pseudomonas	0.00% 0/4	0.00% 0/6	3.4% 1/29 • Number of events 1	0.00% 0/25
Injury, poisoning and procedural complications Medication error	0.00% 0/4	0.00% 0/6	0.00% 0/29	4.0% 1/25 • Number of events 2
Investigations Blood bilirubin increased	0.00% 0/4	0.00% 0/6	3.4% 1/29 • Number of events 1	0.00% 0/25
Investigations Blood creatinine increased	0.00% 0/4	0.00% 0/6	6.9% 2/29 • Number of events 2	0.00% 0/25
Investigations Ejection fraction decreased	0.00% 0/4	0.00% 0/6	0.00% 0/29	4.0% 1/25 • Number of events 1
Investigations Haemoglobin decreased	0.00% 0/4	0.00% 0/6	3.4% 1/29 • Number of events 1	0.00% 0/25
Metabolism and nutrition disorders Anorexia	0.00% 0/4	0.00% 0/6	0.00% 0/29	4.0% 1/25 • Number of events 1
Metabolism and nutrition disorders Dehydration	0.00% 0/4	0.00% 0/6	6.9% 2/29 • Number of events 4	12.0% 3/25 • Number of events 4
Metabolism and nutrition disorders Hypercalcaemia	0.00% 0/4	0.00% 0/6	3.4% 1/29 • Number of events 2	0.00% 0/25
Metabolism and nutrition disorders Hypomagnesaemia	0.00% 0/4	0.00% 0/6	6.9% 2/29 • Number of events 3	0.00% 0/25
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant pleural effusion	0.00% 0/4	0.00% 0/6	3.4% 1/29 • Number of events 1	0.00% 0/25
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to meninges	0.00% 0/4	0.00% 0/6	0.00% 0/29	4.0% 1/25 • Number of events 1
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Pericardial effusion malignant	0.00% 0/4	16.7% 1/6 • Number of events 1	3.4% 1/29 • Number of events 1	0.00% 0/25
Nervous system disorders Cerebral haemorrhage	0.00% 0/4	0.00% 0/6	0.00% 0/29	4.0% 1/25 • Number of events 1
Nervous system disorders Cerebral ischaemia	0.00% 0/4	0.00% 0/6	0.00% 0/29	8.0% 2/25 • Number of events 2
Nervous system disorders Convulsion	0.00% 0/4	0.00% 0/6	0.00% 0/29	4.0% 1/25 • Number of events 1
Nervous system disorders Grand mal convulsion	0.00% 0/4	0.00% 0/6	3.4% 1/29 • Number of events 1	0.00% 0/25
Nervous system disorders Partial seizures	0.00% 0/4	0.00% 0/6	0.00% 0/29	4.0% 1/25 • Number of events 1
Nervous system disorders Peripheral motor neuropathy	0.00% 0/4	0.00% 0/6	3.4% 1/29 • Number of events 1	0.00% 0/25
Psychiatric disorders Confusional state	0.00% 0/4	0.00% 0/6	3.4% 1/29 • Number of events 1	0.00% 0/25
Renal and urinary disorders Renal failure acute	0.00% 0/4	0.00% 0/6	3.4% 1/29 • Number of events 1	0.00% 0/25
Respiratory, thoracic and mediastinal disorders Dyspnoea	25.0% 1/4 • Number of events 1	0.00% 0/6	6.9% 2/29 • Number of events 2	4.0% 1/25 • Number of events 2
Respiratory, thoracic and mediastinal disorders Hypoxia	0.00% 0/4	0.00% 0/6	3.4% 1/29 • Number of events 1	0.00% 0/25
Vascular disorders Thrombophlebitis superficial	0.00% 0/4	16.7% 1/6 • Number of events 1	0.00% 0/29	0.00% 0/25

Other adverse events

Other adverse events
Measure	Gemcitabine/Carboplatin/Cetuximab (GCC) n=4 participants at risk Gemcitabine: 1000 mg/m\^2 on Days 1 and 8 of each 3-week cycle for a total of 6 cycles (18 weeks). Cetuximab: Initial dose of 400 mg/m\^2 on Day 1 of Cycle 1, and subsequent doses of 250 mg/m\^2 Q1W of each 3-week cycle for a total of 6 cycles (18 weeks). Later administered at 500 mg/m\^2 Q2W in the subsequent cycles (2-week cycles). Carboplatin: AUC = 5 on Day 1 of each 3-week cycle for a total of 6 cycles (18 weeks). Treatment was continued until disease progression, unacceptable toxicity, withdrawal of consent or any other discontinuation criteria were met.	GCC Plus Cixutumumab n=6 participants at risk Gemcitabine: 1000 mg/m\^2 on Days 1 and 8 of each 3-week cycle for a total of 6 cycles (18 weeks). Cetuximab: Initial dose of 400 mg/m\^2 on Day 1 of Cycle 1, and subsequent doses of 250 mg/m\^2 Q1W of each 3-week cycle for a total of 6 cycles (18 weeks). Later administered at 500 mg/m\^2 Q2W in the subsequent cycles (2-week cycles). Carboplatin: AUC = 5 on Day 1 of each 3-week cycle for a total of 6 cycles (18 weeks). Cixutumumab: 6 mg/kg IV infusion Q1W on Days 1, 8, and 15 of each 3-week cycle for a total of 6 cycles (18 weeks). Later administered at 10 mg/kg IV Q2W in the subsequent cycles (2-week cycles). Treatment was continued until disease progression, unacceptable toxicity, withdrawal of consent or any other discontinuation criteria were met.	Gemcitabine/Cisplatin/Cetuximab (GCiC) n=29 participants at risk Gemcitabine: 1000 mg/m\^2 on Days 1 and 8 of each 3-week cycle for a total of 6 cycles (18 weeks). Cisplatin: 75 mg/m\^2 on Day 1 of each 3-week cycle for a total of 6 cycles (18 weeks). Cetuximab: Initial dose of 400 mg/m\^2 on Day 1 of Cycle 1, and subsequent doses of 250 mg/m\^2 Q1W of each 3-week cycle for a total of 6 cycles (18 weeks). Later administered at 500 mg/m\^2 Q2W in the subsequent cycles (2-week cycles). Treatment was continued until disease progression, unacceptable toxicity, withdrawal of consent or any other discontinuation criteria were met.	GCiC Plus Cixutumumab n=25 participants at risk Gemcitabine: 1000 mg/m\^2 on Days 1 and 8 of each 3-week cycle for a total of 6 cycles (18 weeks). Cisplatin: 75 mg/m\^2 on Day 1 of each 3-week cycle for a total of 6 cycles (18 weeks). Cetuximab: Initial dose of 400 mg/m\^2 on Day 1 of Cycle 1, and subsequent doses of 250 mg/m\^2 Q1W of each 3-week cycle for a total of 6 cycles (18 weeks). Later administered at 500 mg/m\^2 Q2W in the subsequent cycles (2-week cycles). Cixutumumab: 6 mg/kg IV infusion Q1W on Days 1, 8, and 15 of each 3-week cycle for a total of 6 cycles (18 weeks). Later administered at 10 mg/kg IV Q2W in the subsequent cycles (2-week cycles). Treatment was continued until disease progression, unacceptable toxicity, withdrawal of consent or any other discontinuation criteria were met.
Blood and lymphatic system disorders Anaemia	50.0% 2/4 • Number of events 2	16.7% 1/6 • Number of events 1	34.5% 10/29 • Number of events 31	36.0% 9/25 • Number of events 27
Blood and lymphatic system disorders Leukopenia	25.0% 1/4 • Number of events 1	33.3% 2/6 • Number of events 2	6.9% 2/29 • Number of events 2	0.00% 0/25
Blood and lymphatic system disorders Lymphopenia	0.00% 0/4	0.00% 0/6	6.9% 2/29 • Number of events 3	0.00% 0/25
Blood and lymphatic system disorders Neutropenia	25.0% 1/4 • Number of events 3	66.7% 4/6 • Number of events 7	58.6% 17/29 • Number of events 44	48.0% 12/25 • Number of events 22
Blood and lymphatic system disorders Pancytopenia	25.0% 1/4 • Number of events 1	0.00% 0/6	0.00% 0/29	0.00% 0/25
Blood and lymphatic system disorders Thrombocytopenia	25.0% 1/4 • Number of events 4	33.3% 2/6 • Number of events 5	62.1% 18/29 • Number of events 42	76.0% 19/25 • Number of events 55
Ear and labyrinth disorders Ear discomfort	0.00% 0/4	0.00% 0/6	6.9% 2/29 • Number of events 2	4.0% 1/25 • Number of events 1
Ear and labyrinth disorders Hypoacusis	0.00% 0/4	0.00% 0/6	3.4% 1/29 • Number of events 1	8.0% 2/25 • Number of events 2
Ear and labyrinth disorders Tinnitus	0.00% 0/4	0.00% 0/6	17.2% 5/29 • Number of events 9	8.0% 2/25 • Number of events 2
Eye disorders Photopsia	0.00% 0/4	0.00% 0/6	0.00% 0/29	8.0% 2/25 • Number of events 2
Gastrointestinal disorders Abdominal pain	0.00% 0/4	0.00% 0/6	10.3% 3/29 • Number of events 3	8.0% 2/25 • Number of events 2
Gastrointestinal disorders Abdominal pain upper	0.00% 0/4	0.00% 0/6	10.3% 3/29 • Number of events 4	16.0% 4/25 • Number of events 7
Gastrointestinal disorders Constipation	50.0% 2/4 • Number of events 6	33.3% 2/6 • Number of events 6	58.6% 17/29 • Number of events 25	68.0% 17/25 • Number of events 26
Gastrointestinal disorders Diarrhoea	100.0% 4/4 • Number of events 7	33.3% 2/6 • Number of events 5	44.8% 13/29 • Number of events 20	36.0% 9/25 • Number of events 22
Gastrointestinal disorders Dry mouth	0.00% 0/4	16.7% 1/6 • Number of events 1	10.3% 3/29 • Number of events 3	4.0% 1/25 • Number of events 1
Gastrointestinal disorders Dyspepsia	25.0% 1/4 • Number of events 1	0.00% 0/6	3.4% 1/29 • Number of events 1	20.0% 5/25 • Number of events 5
Gastrointestinal disorders Gastrooesophageal reflux disease	25.0% 1/4 • Number of events 1	16.7% 1/6 • Number of events 1	3.4% 1/29 • Number of events 1	8.0% 2/25 • Number of events 2
Gastrointestinal disorders Gingival bleeding	0.00% 0/4	16.7% 1/6 • Number of events 1	0.00% 0/29	8.0% 2/25 • Number of events 2
Gastrointestinal disorders Gingival pain	0.00% 0/4	16.7% 1/6 • Number of events 1	0.00% 0/29	0.00% 0/25
Gastrointestinal disorders Haemorrhoidal haemorrhage	0.00% 0/4	16.7% 1/6 • Number of events 1	3.4% 1/29 • Number of events 1	0.00% 0/25
Gastrointestinal disorders Nausea	75.0% 3/4 • Number of events 11	50.0% 3/6 • Number of events 5	51.7% 15/29 • Number of events 35	60.0% 15/25 • Number of events 28
Gastrointestinal disorders Oral pain	0.00% 0/4	0.00% 0/6	3.4% 1/29 • Number of events 1	8.0% 2/25 • Number of events 4
Gastrointestinal disorders Rectal haemorrhage	0.00% 0/4	0.00% 0/6	0.00% 0/29	12.0% 3/25 • Number of events 4
Gastrointestinal disorders Stomatitis	25.0% 1/4 • Number of events 2	50.0% 3/6 • Number of events 8	37.9% 11/29 • Number of events 18	60.0% 15/25 • Number of events 21
Gastrointestinal disorders Vomiting	50.0% 2/4 • Number of events 4	0.00% 0/6	31.0% 9/29 • Number of events 13	24.0% 6/25 • Number of events 8
General disorders Asthenia	0.00% 0/4	0.00% 0/6	10.3% 3/29 • Number of events 4	12.0% 3/25 • Number of events 4
General disorders Catheter site pain	0.00% 0/4	16.7% 1/6 • Number of events 1	0.00% 0/29	4.0% 1/25 • Number of events 1
General disorders Catheter thrombosis	0.00% 0/4	0.00% 0/6	3.4% 1/29 • Number of events 1	8.0% 2/25 • Number of events 2
General disorders Chills	0.00% 0/4	0.00% 0/6	6.9% 2/29 • Number of events 2	4.0% 1/25 • Number of events 2
General disorders Early satiety	0.00% 0/4	16.7% 1/6 • Number of events 1	0.00% 0/29	0.00% 0/25
General disorders Fatigue	100.0% 4/4 • Number of events 18	66.7% 4/6 • Number of events 12	72.4% 21/29 • Number of events 28	68.0% 17/25 • Number of events 34
General disorders Infusion related reaction	0.00% 0/4	33.3% 2/6 • Number of events 2	6.9% 2/29 • Number of events 2	0.00% 0/25
General disorders Oedema peripheral	25.0% 1/4 • Number of events 1	0.00% 0/6	17.2% 5/29 • Number of events 9	8.0% 2/25 • Number of events 2
General disorders Pain	0.00% 0/4	0.00% 0/6	6.9% 2/29 • Number of events 2	0.00% 0/25
General disorders Performance status decreased	0.00% 0/4	0.00% 0/6	10.3% 3/29 • Number of events 4	0.00% 0/25
General disorders Pyrexia	0.00% 0/4	16.7% 1/6 • Number of events 1	10.3% 3/29 • Number of events 4	0.00% 0/25
General disorders Xerosis	0.00% 0/4	0.00% 0/6	0.00% 0/29	8.0% 2/25 • Number of events 2
Infections and infestations Catheter site infection	0.00% 0/4	0.00% 0/6	6.9% 2/29 • Number of events 2	0.00% 0/25
Infections and infestations Cellulitis	0.00% 0/4	0.00% 0/6	6.9% 2/29 • Number of events 3	0.00% 0/25
Infections and infestations Incision site infection	0.00% 0/4	16.7% 1/6 • Number of events 1	0.00% 0/29	0.00% 0/25
Infections and infestations Oral candidiasis	0.00% 0/4	0.00% 0/6	10.3% 3/29 • Number of events 5	4.0% 1/25 • Number of events 1
Infections and infestations Paronychia	25.0% 1/4 • Number of events 1	16.7% 1/6 • Number of events 2	6.9% 2/29 • Number of events 8	20.0% 5/25 • Number of events 9
Infections and infestations Pharyngitis	25.0% 1/4 • Number of events 1	0.00% 0/6	0.00% 0/29	0.00% 0/25
Infections and infestations Pneumonia	0.00% 0/4	0.00% 0/6	3.4% 1/29 • Number of events 1	8.0% 2/25 • Number of events 3
Infections and infestations Upper respiratory tract infection	25.0% 1/4 • Number of events 1	0.00% 0/6	3.4% 1/29 • Number of events 1	4.0% 1/25 • Number of events 1
Infections and infestations Urinary tract infection	25.0% 1/4 • Number of events 1	0.00% 0/6	3.4% 1/29 • Number of events 1	8.0% 2/25 • Number of events 3
Injury, poisoning and procedural complications Contusion	0.00% 0/4	0.00% 0/6	6.9% 2/29 • Number of events 2	8.0% 2/25 • Number of events 2
Injury, poisoning and procedural complications Excoriation	25.0% 1/4 • Number of events 1	0.00% 0/6	0.00% 0/29	0.00% 0/25
Injury, poisoning and procedural complications Fall	0.00% 0/4	0.00% 0/6	0.00% 0/29	8.0% 2/25 • Number of events 2
Injury, poisoning and procedural complications Incision site pain	0.00% 0/4	16.7% 1/6 • Number of events 1	0.00% 0/29	0.00% 0/25
Investigations Alanine aminotransferase increased	0.00% 0/4	16.7% 1/6 • Number of events 2	3.4% 1/29 • Number of events 1	0.00% 0/25
Investigations Aspartate aminotransferase increased	0.00% 0/4	16.7% 1/6 • Number of events 1	6.9% 2/29 • Number of events 2	0.00% 0/25
Investigations Blood amylase increased	25.0% 1/4 • Number of events 2	0.00% 0/6	6.9% 2/29 • Number of events 3	8.0% 2/25 • Number of events 3
Investigations Blood creatinine increased	0.00% 0/4	0.00% 0/6	10.3% 3/29 • Number of events 4	16.0% 4/25 • Number of events 5
Investigations Haemoglobin decreased	0.00% 0/4	0.00% 0/6	13.8% 4/29 • Number of events 16	0.00% 0/25
Investigations Lipase increased	25.0% 1/4 • Number of events 1	0.00% 0/6	10.3% 3/29 • Number of events 4	8.0% 2/25 • Number of events 6
Investigations Neutrophil count decreased	0.00% 0/4	0.00% 0/6	6.9% 2/29 • Number of events 2	8.0% 2/25 • Number of events 2
Investigations Weight decreased	0.00% 0/4	16.7% 1/6 • Number of events 1	41.4% 12/29 • Number of events 15	36.0% 9/25 • Number of events 10
Investigations White blood cell count decreased	0.00% 0/4	0.00% 0/6	6.9% 2/29 • Number of events 5	8.0% 2/25 • Number of events 3
Metabolism and nutrition disorders Anorexia	25.0% 1/4 • Number of events 1	33.3% 2/6 • Number of events 2	34.5% 10/29 • Number of events 16	40.0% 10/25 • Number of events 14
Metabolism and nutrition disorders Decreased appetite	25.0% 1/4 • Number of events 1	0.00% 0/6	3.4% 1/29 • Number of events 1	8.0% 2/25 • Number of events 2
Metabolism and nutrition disorders Dehydration	0.00% 0/4	0.00% 0/6	10.3% 3/29 • Number of events 3	20.0% 5/25 • Number of events 5
Metabolism and nutrition disorders Hyperglycaemia	25.0% 1/4 • Number of events 1	16.7% 1/6 • Number of events 1	20.7% 6/29 • Number of events 11	28.0% 7/25 • Number of events 21
Metabolism and nutrition disorders Hypoalbuminaemia	0.00% 0/4	0.00% 0/6	13.8% 4/29 • Number of events 5	4.0% 1/25 • Number of events 3
Metabolism and nutrition disorders Hypocalcaemia	0.00% 0/4	0.00% 0/6	20.7% 6/29 • Number of events 14	4.0% 1/25 • Number of events 1
Metabolism and nutrition disorders Hypokalaemia	50.0% 2/4 • Number of events 2	0.00% 0/6	24.1% 7/29 • Number of events 11	8.0% 2/25 • Number of events 2
Metabolism and nutrition disorders Hypomagnesaemia	25.0% 1/4 • Number of events 3	0.00% 0/6	48.3% 14/29 • Number of events 49	36.0% 9/25 • Number of events 22
Metabolism and nutrition disorders Hyponatraemia	0.00% 0/4	0.00% 0/6	13.8% 4/29 • Number of events 7	4.0% 1/25 • Number of events 1
Musculoskeletal and connective tissue disorders Arthralgia	25.0% 1/4 • Number of events 1	16.7% 1/6 • Number of events 4	10.3% 3/29 • Number of events 4	0.00% 0/25
Musculoskeletal and connective tissue disorders Back pain	25.0% 1/4 • Number of events 1	0.00% 0/6	17.2% 5/29 • Number of events 7	16.0% 4/25 • Number of events 5
Musculoskeletal and connective tissue disorders Bone pain	0.00% 0/4	0.00% 0/6	3.4% 1/29 • Number of events 1	12.0% 3/25 • Number of events 3
Musculoskeletal and connective tissue disorders Flank pain	0.00% 0/4	0.00% 0/6	6.9% 2/29 • Number of events 3	0.00% 0/25
Musculoskeletal and connective tissue disorders Muscle spasms	0.00% 0/4	16.7% 1/6 • Number of events 1	0.00% 0/29	16.0% 4/25 • Number of events 4
Musculoskeletal and connective tissue disorders Muscular weakness	0.00% 0/4	0.00% 0/6	0.00% 0/29	8.0% 2/25 • Number of events 2
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	25.0% 1/4 • Number of events 1	0.00% 0/6	17.2% 5/29 • Number of events 5	12.0% 3/25 • Number of events 4
Musculoskeletal and connective tissue disorders Musculoskeletal pain	0.00% 0/4	16.7% 1/6 • Number of events 2	6.9% 2/29 • Number of events 2	8.0% 2/25 • Number of events 2
Musculoskeletal and connective tissue disorders Pain in extremity	25.0% 1/4 • Number of events 3	16.7% 1/6 • Number of events 2	17.2% 5/29 • Number of events 6	16.0% 4/25 • Number of events 4
Nervous system disorders Balance disorder	0.00% 0/4	0.00% 0/6	0.00% 0/29	12.0% 3/25 • Number of events 3
Nervous system disorders Dizziness	25.0% 1/4 • Number of events 1	0.00% 0/6	27.6% 8/29 • Number of events 14	16.0% 4/25 • Number of events 5
Nervous system disorders Dizziness postural	25.0% 1/4 • Number of events 1	0.00% 0/6	0.00% 0/29	0.00% 0/25
Nervous system disorders Dysgeusia	0.00% 0/4	16.7% 1/6 • Number of events 1	27.6% 8/29 • Number of events 9	24.0% 6/25 • Number of events 7
Nervous system disorders Headache	0.00% 0/4	16.7% 1/6 • Number of events 1	3.4% 1/29 • Number of events 1	12.0% 3/25 • Number of events 3
Nervous system disorders Peripheral sensory neuropathy	0.00% 0/4	16.7% 1/6 • Number of events 2	24.1% 7/29 • Number of events 11	16.0% 4/25 • Number of events 6
Nervous system disorders Restless legs syndrome	0.00% 0/4	0.00% 0/6	3.4% 1/29 • Number of events 1	8.0% 2/25 • Number of events 2
Nervous system disorders Somnolence	0.00% 0/4	0.00% 0/6	0.00% 0/29	8.0% 2/25 • Number of events 2
Nervous system disorders Tremor	25.0% 1/4 • Number of events 1	0.00% 0/6	0.00% 0/29	4.0% 1/25 • Number of events 1
Psychiatric disorders Anxiety	0.00% 0/4	0.00% 0/6	10.3% 3/29 • Number of events 3	4.0% 1/25 • Number of events 1
Psychiatric disorders Depression	0.00% 0/4	0.00% 0/6	10.3% 3/29 • Number of events 3	20.0% 5/25 • Number of events 5
Psychiatric disorders Insomnia	0.00% 0/4	0.00% 0/6	6.9% 2/29 • Number of events 2	12.0% 3/25 • Number of events 3
Renal and urinary disorders Dysuria	25.0% 1/4 • Number of events 1	0.00% 0/6	3.4% 1/29 • Number of events 3	0.00% 0/25
Renal and urinary disorders Pollakiuria	25.0% 1/4 • Number of events 1	0.00% 0/6	3.4% 1/29 • Number of events 1	4.0% 1/25 • Number of events 1
Renal and urinary disorders Renal failure acute	0.00% 0/4	0.00% 0/6	0.00% 0/29	8.0% 2/25 • Number of events 4
Reproductive system and breast disorders Prostatitis	0.00% 0/3	25.0% 1/4 • Number of events 1	0.00% 0/16	0.00% 0/14
Respiratory, thoracic and mediastinal disorders Cough	50.0% 2/4 • Number of events 4	50.0% 3/6 • Number of events 6	17.2% 5/29 • Number of events 6	20.0% 5/25 • Number of events 5
Respiratory, thoracic and mediastinal disorders Dysphonia	0.00% 0/4	0.00% 0/6	3.4% 1/29 • Number of events 1	8.0% 2/25 • Number of events 2
Respiratory, thoracic and mediastinal disorders Dyspnoea	25.0% 1/4 • Number of events 2	50.0% 3/6 • Number of events 7	24.1% 7/29 • Number of events 9	16.0% 4/25 • Number of events 5
Respiratory, thoracic and mediastinal disorders Dyspnoea exertional	0.00% 0/4	16.7% 1/6 • Number of events 2	0.00% 0/29	4.0% 1/25 • Number of events 1
Respiratory, thoracic and mediastinal disorders Epistaxis	75.0% 3/4 • Number of events 4	50.0% 3/6 • Number of events 5	31.0% 9/29 • Number of events 12	60.0% 15/25 • Number of events 20
Respiratory, thoracic and mediastinal disorders Haemoptysis	0.00% 0/4	0.00% 0/6	6.9% 2/29 • Number of events 2	8.0% 2/25 • Number of events 3
Respiratory, thoracic and mediastinal disorders Hiccups	0.00% 0/4	0.00% 0/6	10.3% 3/29 • Number of events 3	12.0% 3/25 • Number of events 3
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	0.00% 0/4	0.00% 0/6	6.9% 2/29 • Number of events 2	4.0% 1/25 • Number of events 1
Respiratory, thoracic and mediastinal disorders Paranasal sinus hypersecretion	0.00% 0/4	0.00% 0/6	6.9% 2/29 • Number of events 2	8.0% 2/25 • Number of events 3
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.00% 0/4	0.00% 0/6	6.9% 2/29 • Number of events 3	0.00% 0/25
Skin and subcutaneous tissue disorders Alopecia	0.00% 0/4	0.00% 0/6	20.7% 6/29 • Number of events 6	28.0% 7/25 • Number of events 8
Skin and subcutaneous tissue disorders Decubitus ulcer	0.00% 0/4	0.00% 0/6	0.00% 0/29	8.0% 2/25 • Number of events 2
Skin and subcutaneous tissue disorders Dermatitis acneiform	100.0% 4/4 • Number of events 8	83.3% 5/6 • Number of events 12	41.4% 12/29 • Number of events 21	32.0% 8/25 • Number of events 12
Skin and subcutaneous tissue disorders Dermatitis contact	25.0% 1/4 • Number of events 1	0.00% 0/6	0.00% 0/29	0.00% 0/25
Skin and subcutaneous tissue disorders Dry skin	25.0% 1/4 • Number of events 1	33.3% 2/6 • Number of events 3	17.2% 5/29 • Number of events 7	36.0% 9/25 • Number of events 13
Skin and subcutaneous tissue disorders Erythema	25.0% 1/4 • Number of events 2	0.00% 0/6	3.4% 1/29 • Number of events 2	0.00% 0/25
Skin and subcutaneous tissue disorders Nail disorder	25.0% 1/4 • Number of events 1	0.00% 0/6	0.00% 0/29	8.0% 2/25 • Number of events 2
Skin and subcutaneous tissue disorders Night sweats	25.0% 1/4 • Number of events 1	0.00% 0/6	3.4% 1/29 • Number of events 1	0.00% 0/25
Skin and subcutaneous tissue disorders Purpura	0.00% 0/4	16.7% 1/6 • Number of events 1	0.00% 0/29	0.00% 0/25
Skin and subcutaneous tissue disorders Rash	0.00% 0/4	33.3% 2/6 • Number of events 4	48.3% 14/29 • Number of events 25	68.0% 17/25 • Number of events 35
Skin and subcutaneous tissue disorders Skin fissures	0.00% 0/4	16.7% 1/6 • Number of events 1	24.1% 7/29 • Number of events 12	48.0% 12/25 • Number of events 14
Vascular disorders Deep vein thrombosis	25.0% 1/4 • Number of events 1	0.00% 0/6	20.7% 6/29 • Number of events 6	8.0% 2/25 • Number of events 2
Vascular disorders Flushing	25.0% 1/4 • Number of events 1	0.00% 0/6	3.4% 1/29 • Number of events 1	0.00% 0/25
Vascular disorders Hypotension	0.00% 0/4	0.00% 0/6	17.2% 5/29 • Number of events 5	4.0% 1/25 • Number of events 1
Vascular disorders Thrombophlebitis superficial	0.00% 0/4	16.7% 1/6 • Number of events 1	0.00% 0/29	0.00% 0/25

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 publication 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