Trial Outcomes & Findings for Study Using IMC-A12 (Cixutumumab) With or Without Cetuximab in Participants With Metastatic Colorectal Cancer Who Have Failed a Treatment Regimen That Consisted of a Prior Anti-EGFR Therapy (NCT NCT00503685)

Last Updated: 2018-06-06

Results Overview

ORR is the percentage of participants with a confirmed CR or PR, as classified by the investigators according to the Response Evaluation Criteria In Solid Tumors (RECIST) criteria version 1.0. CR is the disappearance of all target and non-target lesions; PR is a ≥30% decrease in sum of longest diameter of target lesions without new lesion and progression of non-target lesions. ORR is calculated as a total number of participants with CR or PR from start of the treatment until disease progression or recurrence divided by the total number of participants treated, then multiplied by 100.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

65 participants

Primary outcome timeframe

Start of randomization/treatment to date of objective progressive disease (PD) up to 28.3 weeks

Results posted on

2018-06-06

Participant Flow

Participants with progressive disease (PD) or death are considered having completed study.

Participant milestones

Participant milestones
Measure	IMC-A12 Participants received 10 milligrams/kilogram (mg/kg) IMC-A12 intravenous infusion over 1 hour every 2 weeks until there was evidence of PD, unacceptable toxicity, or withdrawal of consent.	IMC-A12 + Cetuximab Participants received cetuximab 500 milligrams/square meter (mg/m²) intravenous infusion over 2 hours followed by 10 mg/kg IMC-A12 intravenous infusion over 1 hour. This sequence was repeated every 2 weeks until there was evidence of PD, unacceptable toxicity, or withdrawal of consent.	IMC-A12 + Cetuximab (K-ras Wild-type) Participants with Kirsten rat sarcoma (K-ras) wild-type who experienced confirmed partial response (PR) or stable disease (SD) ≥ 24 weeks on a prior anti-epidermal growth factor receptor (EGFR)-containing therapy followed by disease progression were enrolled in this arm. Participants received cetuximab 500 mg/m² intravenous infusion over 2 hours followed by 10 mg/kg IMC-A12 intravenous infusion over 1 hour. This sequence was repeated every 2 weeks until there was evidence of PD, unacceptable toxicity, or withdrawal of consent.
Overall Study STARTED	23	22	20
Overall Study Received at Least 1 Dose of Study Drug	23	21	20
Overall Study COMPLETED	23	19	18
Overall Study NOT COMPLETED	0	3	2

Reasons for withdrawal

Reasons for withdrawal
Measure	IMC-A12 + Cetuximab Participants received cetuximab 500 milligrams/square meter (mg/m²) intravenous infusion over 2 hours followed by 10 mg/kg IMC-A12 intravenous infusion over 1 hour. This sequence was repeated every 2 weeks until there was evidence of PD, unacceptable toxicity, or withdrawal of consent.	IMC-A12 + Cetuximab (K-ras Wild-type) Participants with Kirsten rat sarcoma (K-ras) wild-type who experienced confirmed partial response (PR) or stable disease (SD) ≥ 24 weeks on a prior anti-epidermal growth factor receptor (EGFR)-containing therapy followed by disease progression were enrolled in this arm. Participants received cetuximab 500 mg/m² intravenous infusion over 2 hours followed by 10 mg/kg IMC-A12 intravenous infusion over 1 hour. This sequence was repeated every 2 weeks until there was evidence of PD, unacceptable toxicity, or withdrawal of consent.
Overall Study Adverse Event	0	2
Overall Study Withdrawal by Subject	1	0
Overall Study Protocol Violation	1	0
Overall Study Eligibility Criteria Not Met	1	0

Baseline Characteristics

Study Using IMC-A12 (Cixutumumab) With or Without Cetuximab in Participants With Metastatic Colorectal Cancer Who Have Failed a Treatment Regimen That Consisted of a Prior Anti-EGFR Therapy

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	IMC-A12 n=23 Participants Participants received 10 mg/kg IMC-A12 intravenous infusion over 1 hour every 2 weeks until there was evidence of PD, unacceptable toxicity, or withdrawal of consent.	IMC-A12 + Cetuximab n=21 Participants Participants received cetuximab 500 mg/m² intravenous infusion over 2 hours followed by 10 mg/kg IMC-A12 intravenous infusion over 1 hour. This sequence was repeated every 2 weeks until there was evidence of PD, unacceptable toxicity, or withdrawal of consent.	IMC-A12 + Cetuximab (K-ras Wild-type) n=20 Participants Participants with K-ras wild-type who experienced confirmed PR or SD ≥ 24 weeks on a prior anti-EGFR-containing therapy followed by disease progression were enrolled in this arm. Participants received cetuximab 500 mg/m² intravenous infusion over 2 hours followed by 10 mg/kg IMC-A12 intravenous infusion over 1 hour. This sequence was repeated every 2 weeks until there was evidence of PD, unacceptable toxicity, or withdrawal of consent.	Total n=64 Participants Total of all reporting groups
Age, Continuous	59.3 years FULL_RANGE 8.94 • n=5 Participants	62.6 years FULL_RANGE 12.40 • n=7 Participants	61.7 years FULL_RANGE 7.89 • n=5 Participants	60.5 years FULL_RANGE 9.84 • n=4 Participants
Sex: Female, Male Female	14 Participants n=5 Participants	9 Participants n=7 Participants	10 Participants n=5 Participants	33 Participants n=4 Participants
Sex: Female, Male Male	9 Participants n=5 Participants	12 Participants n=7 Participants	10 Participants n=5 Participants	31 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants n=5 Participants	3 Participants n=7 Participants	2 Participants n=5 Participants	7 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	21 Participants n=5 Participants	18 Participants n=7 Participants	18 Participants n=5 Participants	57 Participants n=4 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
Race/Ethnicity, Customized White	17 Participants n=5 Participants	17 Participants n=7 Participants	17 Participants n=5 Participants	51 Participants n=4 Participants
Race/Ethnicity, Customized Black	4 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants	8 Participants n=4 Participants
Race/Ethnicity, Customized Asian	1 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	3 Participants n=4 Participants
Race/Ethnicity, Customized Hispanic	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Race/Ethnicity, Customized Unknown or Not Reported	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Region of Enrollment United States	23 Participants n=5 Participants	21 Participants n=7 Participants	20 Participants n=5 Participants	64 Participants n=4 Participants

PRIMARY outcome

Timeframe: Start of randomization/treatment to date of objective progressive disease (PD) up to 28.3 weeks

Population: All randomized/enrolled participants who received at least 1 dose of study drug.

Outcome measures

Outcome measures
Measure	IMC-A12 n=23 Participants Participants received 10 mg/kg IMC-A12 intravenous infusion over 1 hour every 2 weeks until there was evidence of PD, unacceptable toxicity, or withdrawal of consent.	IMC-A12 + Cetuximab n=21 Participants Participants received cetuximab 500 mg/m² intravenous infusion over 2 hours followed by 10 mg/kg IMC-A12 intravenous infusion over 1 hour. This sequence was repeated every 2 weeks until there was evidence of PD, unacceptable toxicity, or withdrawal of consent.	IMC-A12 + Cetuximab (K-ras Wild-type) n=20 Participants Participants with K-ras wild-type who experienced confirmed PR or SD ≥ 24 weeks on a prior anti-EGFR-containing therapy followed by disease progression were enrolled in this arm. Participants received cetuximab 500 mg/m² intravenous infusion over 2 hours followed by 10 mg/kg IMC-A12 intravenous infusion over 1 hour. This sequence was repeated every 2 weeks until there was evidence of PD, unacceptable toxicity, or withdrawal of consent.
Percentage of Participants With Complete Response (CR) or Partial Response [PR, Objective Response Rate (ORR)]	0.0 percentage of participants Interval 0.0 to 14.8	4.8 percentage of participants Interval 0.1 to 23.8	0.0 percentage of participants Interval 0.0 to 16.8

SECONDARY outcome

Timeframe: Randomization/treatment to measured PD up to 28.3 weeks

Population: All randomized/enrolled participants who received at least 1 dose of study drug. The number of participants censored was 0 for IMC-A12 group, 1 for IMC-A12 + cetuximab group and 1 for IMC-A12 + cetuximab (K-ras wild-type) group.

PFS was defined as the duration from the date of randomization/treatment to the date of PD or death from any cause. PD was determined using RECIST criteria version 1.0. PD is ≥20% increase in sum of longest diameter of target lesions or the appearance of new lesions. Participants who had no PD or death at the time of the data inclusion cutoff, PFS was censored at their last tumor assessment prior to the cutoff date. Participants who began a new antitumor treatment before evidence of PD were categorized as PD.

Outcome measures

Outcome measures
Measure	IMC-A12 n=23 Participants Participants received 10 mg/kg IMC-A12 intravenous infusion over 1 hour every 2 weeks until there was evidence of PD, unacceptable toxicity, or withdrawal of consent.	IMC-A12 + Cetuximab n=21 Participants Participants received cetuximab 500 mg/m² intravenous infusion over 2 hours followed by 10 mg/kg IMC-A12 intravenous infusion over 1 hour. This sequence was repeated every 2 weeks until there was evidence of PD, unacceptable toxicity, or withdrawal of consent.	IMC-A12 + Cetuximab (K-ras Wild-type) n=20 Participants Participants with K-ras wild-type who experienced confirmed PR or SD ≥ 24 weeks on a prior anti-EGFR-containing therapy followed by disease progression were enrolled in this arm. Participants received cetuximab 500 mg/m² intravenous infusion over 2 hours followed by 10 mg/kg IMC-A12 intravenous infusion over 1 hour. This sequence was repeated every 2 weeks until there was evidence of PD, unacceptable toxicity, or withdrawal of consent.
Progression-Free Survival (PFS)	5.9 weeks Interval 5.6 to 5.9	6.1 weeks Interval 5.6 to 6.4	9.4 weeks Interval 5.6 to 11.6

SECONDARY outcome

Timeframe: Randomization/treatment to date of death from any cause up to 26.9 months

Population: All randomized/enrolled participants who received at least 1 dose of study drug. The number of participants censored was 5 for IMC-A12 group, 4 for IMC-A12 + cetuximab group and 11 for IMC-A12 + cetuximab (K-ras wild-type) group.

OS is defined as the duration from the date of randomization/treatment to the date of death from any cause. Participants who were alive at the time of the data inclusion cutoff, OS was censored at the last date the participant was known to be alive.

Outcome measures

Outcome measures
Measure	IMC-A12 n=23 Participants Participants received 10 mg/kg IMC-A12 intravenous infusion over 1 hour every 2 weeks until there was evidence of PD, unacceptable toxicity, or withdrawal of consent.	IMC-A12 + Cetuximab n=21 Participants Participants received cetuximab 500 mg/m² intravenous infusion over 2 hours followed by 10 mg/kg IMC-A12 intravenous infusion over 1 hour. This sequence was repeated every 2 weeks until there was evidence of PD, unacceptable toxicity, or withdrawal of consent.	IMC-A12 + Cetuximab (K-ras Wild-type) n=20 Participants Participants with K-ras wild-type who experienced confirmed PR or SD ≥ 24 weeks on a prior anti-EGFR-containing therapy followed by disease progression were enrolled in this arm. Participants received cetuximab 500 mg/m² intravenous infusion over 2 hours followed by 10 mg/kg IMC-A12 intravenous infusion over 1 hour. This sequence was repeated every 2 weeks until there was evidence of PD, unacceptable toxicity, or withdrawal of consent.
Overall Survival (OS)	5.7 months Interval 3.4 to 7.9	4.5 months Interval 2.8 to 13.3	10.9 months Interval 5.5 to Upper limit of 95% confidence interval was not estimable due to high censoring rate.

SECONDARY outcome

Timeframe: Time from randomization/treatment to first date of PD up to 28.3 weeks

Population: All randomized/enrolled participants who received at least 1 dose of the study drug and achieved SD or better. The number of participants censored was 0 for IMC-A12 group, 0 for IMC-A12 + cetuximab group and 1 for IMC-A12 + cetuximab (K-ras wild-type) group.

The duration of SD is measured from the date of randomization/treatment until the date of PD. SD is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. RECIST criteria version 1.0 was used to asses PR and PD. PR is ≥30% decrease in sum of longest diameter of target lesions. PD is ≥20% increase in sum of longest diameter of target lesions and/or a new lesion. Participants who had no PD or death at the time of the data inclusion cutoff, duration of SD was censored at their last tumor assessment prior to the cutoff date.

Outcome measures

Outcome measures
Measure	IMC-A12 n=3 Participants Participants received 10 mg/kg IMC-A12 intravenous infusion over 1 hour every 2 weeks until there was evidence of PD, unacceptable toxicity, or withdrawal of consent.	IMC-A12 + Cetuximab n=3 Participants Participants received cetuximab 500 mg/m² intravenous infusion over 2 hours followed by 10 mg/kg IMC-A12 intravenous infusion over 1 hour. This sequence was repeated every 2 weeks until there was evidence of PD, unacceptable toxicity, or withdrawal of consent.	IMC-A12 + Cetuximab (K-ras Wild-type) n=12 Participants Participants with K-ras wild-type who experienced confirmed PR or SD ≥ 24 weeks on a prior anti-EGFR-containing therapy followed by disease progression were enrolled in this arm. Participants received cetuximab 500 mg/m² intravenous infusion over 2 hours followed by 10 mg/kg IMC-A12 intravenous infusion over 1 hour. This sequence was repeated every 2 weeks until there was evidence of PD, unacceptable toxicity, or withdrawal of consent.
Duration of Stable Disease (SD)	11.1 weeks Interval 10.7 to 12.3	15.4 weeks Interval 11.4 to 28.3	11.6 weeks Interval 9.0 to 17.9

SECONDARY outcome

Timeframe: Time of response to time of measured PD or death up to 161 days

Population: Zero participants analyzed. Duration of Response for CR or PR data was not collected for analysis due to N=0 CR and N=1 PR.

The duration of overall response (CR or PR) was defined as the time from first objective status assessment of CR or PR to the first time of PD or death due to any cause. CR, PR and PD were determined using RECIST criteria version 1.0. CR is the disappearance of all target and non-target lesions; PR is a ≥30% decrease in sum of longest diameter of target lesions without new lesion and progression of non-target lesions; PD is ≥20% increase in sum of longest diameter of target lesions or the appearance of new lesions. For participants with CR or PR who had no PD or death at the time of the data inclusion cutoff, the duration of overall response was censored at their last tumor assessment prior to the cutoff date. Duration of overall response was not analyzed due to low number of participants with CR or PR.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Randomization/treatment up to 26.9 months

Population: All randomized/enrolled participants who received at least 1 dose of study drug.

Data presented are the number of participants who experienced nonserious adverse events (AEs) during the study including the 30-day follow-up. A summary of serious AEs (SAEs) and other non-serious AEs regardless of causality is located in the Reported Adverse Events module.

Outcome measures

Outcome measures
Measure	IMC-A12 n=23 Participants Participants received 10 mg/kg IMC-A12 intravenous infusion over 1 hour every 2 weeks until there was evidence of PD, unacceptable toxicity, or withdrawal of consent.	IMC-A12 + Cetuximab n=21 Participants Participants received cetuximab 500 mg/m² intravenous infusion over 2 hours followed by 10 mg/kg IMC-A12 intravenous infusion over 1 hour. This sequence was repeated every 2 weeks until there was evidence of PD, unacceptable toxicity, or withdrawal of consent.	IMC-A12 + Cetuximab (K-ras Wild-type) n=20 Participants Participants with K-ras wild-type who experienced confirmed PR or SD ≥ 24 weeks on a prior anti-EGFR-containing therapy followed by disease progression were enrolled in this arm. Participants received cetuximab 500 mg/m² intravenous infusion over 2 hours followed by 10 mg/kg IMC-A12 intravenous infusion over 1 hour. This sequence was repeated every 2 weeks until there was evidence of PD, unacceptable toxicity, or withdrawal of consent.
Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs)	18 Participants	19 Participants	20 Participants

SECONDARY outcome

Timeframe: Randomization/treatment up to 26.9 months

Population: All randomized/enrolled participants who received at least 1 dose of study drug.

Data presented are the number of participants who experienced serious adverse events (SAEs) or 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 module.

Outcome measures

Outcome measures
Measure	IMC-A12 n=23 Participants Participants received 10 mg/kg IMC-A12 intravenous infusion over 1 hour every 2 weeks until there was evidence of PD, unacceptable toxicity, or withdrawal of consent.	IMC-A12 + Cetuximab n=21 Participants Participants received cetuximab 500 mg/m² intravenous infusion over 2 hours followed by 10 mg/kg IMC-A12 intravenous infusion over 1 hour. This sequence was repeated every 2 weeks until there was evidence of PD, unacceptable toxicity, or withdrawal of consent.	IMC-A12 + Cetuximab (K-ras Wild-type) n=20 Participants Participants with K-ras wild-type who experienced confirmed PR or SD ≥ 24 weeks on a prior anti-EGFR-containing therapy followed by disease progression were enrolled in this arm. Participants received cetuximab 500 mg/m² intravenous infusion over 2 hours followed by 10 mg/kg IMC-A12 intravenous infusion over 1 hour. This sequence was repeated every 2 weeks until there was evidence of PD, unacceptable toxicity, or withdrawal of consent.
Number of Participants Reporting Treatment-Emergent Severe Adverse Events SAEs	7 Participants	6 Participants	4 Participants
Number of Participants Reporting Treatment-Emergent Severe Adverse Events Death Due to PD	1 Participants	0 Participants	0 Participants
Number of Participants Reporting Treatment-Emergent Severe Adverse Events Death Due to SAE	0 Participants	1 Participants	0 Participants

SECONDARY outcome

Timeframe: Week 1 (Initial dose), Week 3 (Dose 2), Week 5 (Dose 3), Week 7 (Dose 4), Week 9 (Dose 5), and Week 11 (Dose 6)

Population: Zero participants analyzed. PK data was not collected for analysis due to the low number of participants in PK.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Week 1 (Initial dose), Week 3 (Dose 2), Week 5 (Dose 3), Week 7 (Dose 4), Week 9 (Dose 5), and Week 11 (Dose 6)

Population: Zero participants analyzed. PK data was not collected for analysis due to the low number of participants in PK.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Week 1 (Initial dose), Week 3 (Dose 2), Week 5 (Dose 3), Week 7 (Dose 4), Week 9 (Dose 5), and Week 11 (Dose 6)

Population: Zero participants analyzed. PK data was not collected for analysis due to the low number of participants in PK.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Treatment up to 26.9 months

Population: Zero participants analyzed. Response rate data was not collected for analysis due to N=0 CR and N=1 PR.

The response rate in participants with K-ras mutations was not collected for analysis.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Randomization/treatment up to 26.9 months

Population: Zero participants analyzed. No data collected for analysis.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Randomization/treatment up to 26.9 months

Population: Zero participants analyzed. No data collected for analysis.

Outcome measures

Outcome data not reported

Adverse Events

IMC-A12

Serious events: 7 serious events

Other events: 18 other events

Deaths: 0 deaths

IMC-A12 + Cetuximab

Serious events: 6 serious events

Other events: 19 other events

Deaths: 0 deaths

IMC-A12 + Cetuximab (K-ras Wild-type)

Serious events: 4 serious events

Other events: 20 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	IMC-A12 n=23 participants at risk Participants received 10 mg/kg IMC-A12 intravenous infusion over 1 hour every 2 weeks until there was evidence of PD, unacceptable toxicity, or withdrawal of consent.	IMC-A12 + Cetuximab n=21 participants at risk Participants received cetuximab 500 mg/m² intravenous infusion over 2 hours followed by 10 mg/kg IMC-A12 intravenous infusion over 1 hour. This sequence was repeated every 2 weeks until there was evidence of PD, unacceptable toxicity, or withdrawal of consent.	IMC-A12 + Cetuximab (K-ras Wild-type) n=20 participants at risk Participants with K-ras wild-type who experienced confirmed PR or SD ≥ 24 weeks on a prior anti-EGFR-containing therapy followed by disease progression were enrolled in this arm. Participants received cetuximab 500 mg/m² intravenous infusion over 2 hours followed by 10 mg/kg IMC-A12 intravenous infusion over 1 hour. This sequence was repeated every 2 weeks until there was evidence of PD, unacceptable toxicity, or withdrawal of consent.
Blood and lymphatic system disorders Anaemia	4.3% 1/23 • Number of events 1	0.00% 0/21	0.00% 0/20
Blood and lymphatic system disorders Thrombocytopenia	0.00% 0/23	0.00% 0/21	5.0% 1/20 • Number of events 1
Gastrointestinal disorders Abdominal pain	8.7% 2/23 • Number of events 3	0.00% 0/21	5.0% 1/20 • Number of events 1
Gastrointestinal disorders Abdominal pain upper	0.00% 0/23	4.8% 1/21 • Number of events 1	0.00% 0/20
Gastrointestinal disorders Constipation	0.00% 0/23	0.00% 0/21	5.0% 1/20 • Number of events 1
Gastrointestinal disorders Haematemesis	0.00% 0/23	4.8% 1/21 • Number of events 1	0.00% 0/20
Gastrointestinal disorders Nausea	4.3% 1/23 • Number of events 1	0.00% 0/21	0.00% 0/20
Gastrointestinal disorders Small intestinal obstruction	4.3% 1/23 • Number of events 1	0.00% 0/21	5.0% 1/20 • Number of events 1
Gastrointestinal disorders Vomiting	4.3% 1/23 • Number of events 1	0.00% 0/21	0.00% 0/20
General disorders Asthenia	8.7% 2/23 • Number of events 2	0.00% 0/21	0.00% 0/20
General disorders Disease progression	8.7% 2/23 • Number of events 2	4.8% 1/21 • Number of events 1	0.00% 0/20
General disorders Fatigue	0.00% 0/23	0.00% 0/21	5.0% 1/20 • Number of events 1
General disorders Infusion related reaction	4.3% 1/23 • Number of events 1	0.00% 0/21	0.00% 0/20
General disorders Pyrexia	0.00% 0/23	4.8% 1/21 • Number of events 1	0.00% 0/20
Hepatobiliary disorders Bile duct obstruction	4.3% 1/23 • Number of events 1	0.00% 0/21	0.00% 0/20
Hepatobiliary disorders Cholangitis	4.3% 1/23 • Number of events 1	0.00% 0/21	0.00% 0/20
Infections and infestations Bacteraemia	0.00% 0/23	4.8% 1/21 • Number of events 1	0.00% 0/20
Infections and infestations Pneumonia	4.3% 1/23 • Number of events 1	0.00% 0/21	0.00% 0/20
Infections and infestations Sepsis	0.00% 0/23	4.8% 1/21 • Number of events 1	0.00% 0/20
Infections and infestations Urinary tract infection	4.3% 1/23 • Number of events 1	0.00% 0/21	0.00% 0/20
Injury, poisoning and procedural complications Fall	4.3% 1/23 • Number of events 1	0.00% 0/21	0.00% 0/20
Injury, poisoning and procedural complications Post procedural bile leak	0.00% 0/23	4.8% 1/21 • Number of events 3	0.00% 0/20
Investigations Aspartate aminotransferase increased	4.3% 1/23 • Number of events 1	0.00% 0/21	0.00% 0/20
Investigations Blood alkaline phosphatase increased	4.3% 1/23 • Number of events 1	0.00% 0/21	0.00% 0/20
Investigations Blood bilirubin increased	0.00% 0/23	4.8% 1/21 • Number of events 1	0.00% 0/20
Metabolism and nutrition disorders Dehydration	4.3% 1/23 • Number of events 1	4.8% 1/21 • Number of events 1	0.00% 0/20
Metabolism and nutrition disorders Hyperglycaemia	4.3% 1/23 • Number of events 1	0.00% 0/21	0.00% 0/20
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/23	0.00% 0/21	5.0% 1/20 • Number of events 1
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/23	0.00% 0/21	5.0% 1/20 • Number of events 1
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/23	0.00% 0/21	5.0% 1/20 • Number of events 1
Nervous system disorders Headache	0.00% 0/23	4.8% 1/21 • Number of events 1	0.00% 0/20
Renal and urinary disorders Acute prerenal failure	4.3% 1/23 • Number of events 1	0.00% 0/21	0.00% 0/20
Renal and urinary disorders Renal failure acute	0.00% 0/23	4.8% 1/21 • Number of events 1	0.00% 0/20
Renal and urinary disorders Ureteric obstruction	4.3% 1/23 • Number of events 1	0.00% 0/21	0.00% 0/20
Respiratory, thoracic and mediastinal disorders Dyspnoea	4.3% 1/23 • Number of events 1	0.00% 0/21	5.0% 1/20 • Number of events 1
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.00% 0/23	0.00% 0/21	5.0% 1/20 • Number of events 1

Other adverse events

Other adverse events
Measure	IMC-A12 n=23 participants at risk Participants received 10 mg/kg IMC-A12 intravenous infusion over 1 hour every 2 weeks until there was evidence of PD, unacceptable toxicity, or withdrawal of consent.	IMC-A12 + Cetuximab n=21 participants at risk Participants received cetuximab 500 mg/m² intravenous infusion over 2 hours followed by 10 mg/kg IMC-A12 intravenous infusion over 1 hour. This sequence was repeated every 2 weeks until there was evidence of PD, unacceptable toxicity, or withdrawal of consent.	IMC-A12 + Cetuximab (K-ras Wild-type) n=20 participants at risk Participants with K-ras wild-type who experienced confirmed PR or SD ≥ 24 weeks on a prior anti-EGFR-containing therapy followed by disease progression were enrolled in this arm. Participants received cetuximab 500 mg/m² intravenous infusion over 2 hours followed by 10 mg/kg IMC-A12 intravenous infusion over 1 hour. This sequence was repeated every 2 weeks until there was evidence of PD, unacceptable toxicity, or withdrawal of consent.
Blood and lymphatic system disorders Anaemia	4.3% 1/23 • Number of events 1	9.5% 2/21 • Number of events 3	0.00% 0/20
Gastrointestinal disorders Abdominal pain	13.0% 3/23 • Number of events 3	9.5% 2/21 • Number of events 2	5.0% 1/20 • Number of events 1
Gastrointestinal disorders Abdominal pain upper	8.7% 2/23 • Number of events 2	9.5% 2/21 • Number of events 2	5.0% 1/20 • Number of events 1
Gastrointestinal disorders Constipation	17.4% 4/23 • Number of events 4	9.5% 2/21 • Number of events 2	10.0% 2/20 • Number of events 2
Gastrointestinal disorders Diarrhoea	8.7% 2/23 • Number of events 2	19.0% 4/21 • Number of events 6	20.0% 4/20 • Number of events 5
Gastrointestinal disorders Nausea	13.0% 3/23 • Number of events 4	28.6% 6/21 • Number of events 9	15.0% 3/20 • Number of events 3
Gastrointestinal disorders Stomatitis	4.3% 1/23 • Number of events 1	4.8% 1/21 • Number of events 1	15.0% 3/20 • Number of events 3
Gastrointestinal disorders Vomiting	8.7% 2/23 • Number of events 3	14.3% 3/21 • Number of events 5	20.0% 4/20 • Number of events 4
General disorders Fatigue	30.4% 7/23 • Number of events 9	38.1% 8/21 • Number of events 11	40.0% 8/20 • Number of events 9
General disorders Mucosal inflammation	0.00% 0/23	9.5% 2/21 • Number of events 2	0.00% 0/20
General disorders Pyrexia	13.0% 3/23 • Number of events 3	9.5% 2/21 • Number of events 2	5.0% 1/20 • Number of events 1
Infections and infestations Paronychia	0.00% 0/23	4.8% 1/21 • Number of events 2	10.0% 2/20 • Number of events 3
Investigations Blood bilirubin increased	8.7% 2/23 • Number of events 3	4.8% 1/21 • Number of events 1	0.00% 0/20
Investigations Weight decreased	17.4% 4/23 • Number of events 5	9.5% 2/21 • Number of events 3	0.00% 0/20
Metabolism and nutrition disorders Anorexia	13.0% 3/23 • Number of events 3	14.3% 3/21 • Number of events 5	25.0% 5/20 • Number of events 7
Metabolism and nutrition disorders Decreased appetite	8.7% 2/23 • Number of events 2	14.3% 3/21 • Number of events 3	5.0% 1/20 • Number of events 1
Metabolism and nutrition disorders Hypokalaemia	0.00% 0/23	14.3% 3/21 • Number of events 4	0.00% 0/20
Metabolism and nutrition disorders Hypomagnesaemia	0.00% 0/23	19.0% 4/21 • Number of events 10	0.00% 0/20
Musculoskeletal and connective tissue disorders Back pain	13.0% 3/23 • Number of events 4	9.5% 2/21 • Number of events 3	5.0% 1/20 • Number of events 1
Musculoskeletal and connective tissue disorders Myalgia	0.00% 0/23	4.8% 1/21 • Number of events 1	10.0% 2/20 • Number of events 2
Nervous system disorders Dizziness	13.0% 3/23 • Number of events 3	9.5% 2/21 • Number of events 4	5.0% 1/20 • Number of events 1
Nervous system disorders Dysgeusia	8.7% 2/23 • Number of events 2	9.5% 2/21 • Number of events 2	10.0% 2/20 • Number of events 2
Nervous system disorders Headache	4.3% 1/23 • Number of events 1	9.5% 2/21 • Number of events 2	30.0% 6/20 • Number of events 6
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/23	9.5% 2/21 • Number of events 2	5.0% 1/20 • Number of events 1
Respiratory, thoracic and mediastinal disorders Dyspnoea	30.4% 7/23 • Number of events 7	14.3% 3/21 • Number of events 4	5.0% 1/20 • Number of events 1
Respiratory, thoracic and mediastinal disorders Dyspnoea exertional	0.00% 0/23	9.5% 2/21 • Number of events 2	0.00% 0/20
Respiratory, thoracic and mediastinal disorders Epistaxis	4.3% 1/23 • Number of events 1	9.5% 2/21 • Number of events 2	0.00% 0/20
Skin and subcutaneous tissue disorders Dermatitis acneiform	0.00% 0/23	57.1% 12/21 • Number of events 19	45.0% 9/20 • Number of events 14
Skin and subcutaneous tissue disorders Dry skin	0.00% 0/23	14.3% 3/21 • Number of events 3	35.0% 7/20 • Number of events 7
Skin and subcutaneous tissue disorders Nail disorder	0.00% 0/23	4.8% 1/21 • Number of events 1	10.0% 2/20 • Number of events 2
Skin and subcutaneous tissue disorders Pruritus	0.00% 0/23	9.5% 2/21 • Number of events 2	20.0% 4/20 • Number of events 5
Skin and subcutaneous tissue disorders Rash	0.00% 0/23	14.3% 3/21 • Number of events 4	5.0% 1/20 • Number of events 1
Skin and subcutaneous tissue disorders Rash macular	0.00% 0/23	4.8% 1/21 • Number of events 1	30.0% 6/20 • Number of events 7
Vascular disorders Hypertension	0.00% 0/23	0.00% 0/21	10.0% 2/20 • Number of events 2

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