A Study of IMC-A12 in Combination With Sorafenib in Participants With Advanced Cancer of the Liver

PFS is defined as the time from date of first dose of study drug until the date of objective PD or death due to any cause, whichever occurs first. PD defined as a ≥20% increase in the sum of the longest diameter (LD) of target lesions using as reference the smallest sum LD since baseline or ≥1 new lesions. Participants who died without PD were considered to have progressed on the date of death. Participants who were alive and without PD were censored at the time of the last objective tumor assessment. Participants who did not progress and are subsequently lost to follow-up were censored at the date of their last objective tumor assessment before loss to follow-up. Participants who progressed or died after ≥2 missed tumor assessment visits were censored at the date of their last objective tumor assessment before missed assessments. Participants who begin a new anticancer therapy were censored at the date of their last objective tumor assessment before initiation of new therapy.

Time frame: Date of first dose of study drug up PD or death up to 12 months

Population: All randomized participants in Cohort 2 who received any amount of study drug, per the protocol efficacy analysis was only performed for Cohort 2. Participants censored = 10.

Duration of CR or PR was defined as time from first objective assessment of CR or PR until first date of PD or death from any cause. Response was defined using RECIST v 1.0 criteria. CR was defined as disappearance of all target and nontarget lesions and normalization of tumor marker levels. PR was defined as a ≥30% decrease in the sum of LD of target lesions taking as reference the baseline sum LD. PD defined as a ≥20% increase in the sum of LD of target lesions using as reference the smallest sum LD since baseline or ≥1 new lesions. Participants with no PD, who discontinued treatment for toxicity or a reason other than PD, or were lost to follow-up, were censored at date of last tumor assessment. Participants who began new anticancer therapy prior to PD or death were censored at date of last tumor assessment prior to new therapy. Participants who died or had PD after ≥2 missed tumor assessments were censored at date of last tumor assessment prior to the missed assessments

Time frame: Date of first occurrence of CR or PR to first date of PD or death up to 8 months

Population: All randomized participants in Cohort 2 who received any amount of study drug, per the protocol efficacy analysis was only performed for Cohort 2. Participants censored = 1.

Clinically significant events were defined as serious adverse events (SAEs) and other non-serious AEs regardless of causality. A summary of SAEs and other non-serious AEs regardless of causality, is located in the Reported Adverse Events module.

Time frame: First day of treatment up to 22 months

Population: All randomized participants who received any amount of study drug.

OS was defined as the time from the date of first dose of study drug to the date of death from any cause. If the participant was alive at the end of the follow-up period or was lost to follow-up, OS was censored on the last date the participant was known to be alive.

Time frame: Date of first dose of study drug to date of death up to 22 months

Population: All randomized participants in Cohort 2 who received any amount of study drug, per the protocol efficacy analysis was only performed for Cohort 2. Participants censored = 19.

Response was defined using Response Evaluation Criteria In Solid Tumors (RECIST, version 1.0) criteria. CR was defined as the disappearance of all target and nontarget lesions and the normalization of tumor marker levels. PR was defined as having a ≥30% decrease in the sum of LD of target lesions taking as reference the baseline sum LD. Participants who did not have a tumor response assessment for any reason were considered nonresponders and were included in the denominator when calculating the response rate. Percentage of participants was calculated as: CR + PR / total number of participants in the treatment group \* 100.

Time frame: Date of first dose of study drug to PD up to 12 months

Population: All randomized participants in Cohort 2 who received any amount of study drug, per the protocol efficacy analysis was only performed for Cohort 2.

Time frame: Cycle 1, Day 1: Predose, 1 hour (h), 2 h, 168 h, 336 h, and 504 h after start of infusion (immediately prior to Cycle 2)

Population: Zero participants analyzed. No PK analysis was done, the assay used for PK assessment was not reliable and the values obtained could not be used. The samples expired before a new assay was developed, so data were not collected.

Time frame: Cycle 1, Day 1: Predose, 1 h, 2 h, 168 h, 336 h, and 504 h after start of infusion (immediately prior to Cycle 2)

Population: Zero participants analyzed. No PK analysis was done, the assay used for PK assessment was not reliable and the values obtained could not be used. The samples expired before a new assay was developed, so data were not collected.

Time frame: Cycle 3, Day 1: Predose, 2 h, 24 h, 48 h, 72 h, 168 h, 240 h, 336 h and 504 h after start of infusion (immediately prior to Cycle 4)

Population: Zero participants analyzed. No PK analysis was done, the assay used for PK assessment was not reliable and the values obtained could not be used. The samples expired before a new assay was developed, so data were not collected.

Time frame: Cycle 3, Day 1: Predose, 2 h, 24 h, 48 h, 72 h, 168 h, 240 h, 336 h and 504 h after start of infusion (immediately prior to Cycle 4)

Population: Zero participants analyzed. No PK analysis was done, the assay used for PK assessment was not reliable and the values obtained could not be used. The samples expired before a new assay was developed, so data were not collected.

Time frame: Cycle 1, Day 1: Predose, 1 h, 2 h, 168 h, 336 h, and 504 h after start of infusion (immediately prior to Cycle 2)

Population: Zero participants analyzed. No PK analysis was done, the assay used for PK assessment was not reliable and the values obtained could not be used. The samples expired before a new assay was developed, so data were not collected.

Time frame: Cycle 3, Day 1: Predose, 2 h, 24 h, 48 h, 72 h, 168 h, 240 h, 336 h and 504 h after start of infusion (immediately prior to Cycle 4)

Population: Zero participants analyzed. No PK analysis was done, the assay used for PK assessment was not reliable and the values obtained could not be used. The samples expired before a new assay was developed, so data were not collected.

Time frame: Cycle 3, Day 1: Predose, 2 h, 24 h, 48 h, 72 h, 168 h, 240 h, 336 h and 504 h after start of infusion (immediately prior to Cycle 4)

Population: Zero participants analyzed. No PK analysis was done, the assay used for PK assessment was not reliable and the values obtained could not be used. The samples expired before a new assay was developed, so data were not collected.

Time frame: Cycle 1, Day 1: Predose, 1 h, 2 h, 168 h, 336 h, and 504 h after start of infusion (immediately prior to Cycle 2)

Population: Zero participants analyzed. No PK analysis was done, the assay used for PK assessment was not reliable and the values obtained could not be used. The samples expired before a new assay was developed, so data were not collected.

Time frame: Cycle 1, Day 1: Predose, 1 h, 2 h, 168 h, 336 h, and 504 h after start of infusion (immediately prior to Cycle 2)

Population: Zero participants analyzed. No PK analysis was done, the assay used for PK assessment was not reliable and the values obtained could not be used. The samples expired before a new assay was developed, so data were not collected.

Time frame: Cycle 3, Day 1: Predose, 2 h, 24 h, 48 h, 72 h, 168 h, 240 h, 336 h and 504 h after start of infusion (immediately prior to Cycle 4)

Population: Zero participants analyzed. No PK analysis was done, the assay used for PK assessment was not reliable and the values obtained could not be used. The samples expired before a new assay was developed, so data were not collected.

Time frame: Cycle 1, Day 1: Predose, 1 h, 2 h, 168 h, 336 h, and 504 h after start of infusion (immediately prior to Cycle 2)

Population: Zero participants analyzed. No PK analysis was done, the assay used for PK assessment was not reliable and the values obtained could not be used. The samples expired before a new assay was developed, so data were not collected.

Time frame: Cycle 3, Day 1: Predose, 2 h, 24 h, 48 h, 72 h, 168 h, 240 h, 336 h and 504 h after start of infusion (immediately prior to Cycle 4)

Population: Zero participants analyzed. No PK analysis was done, the assay used for PK assessment was not reliable and the values obtained could not be used. The samples expired before a new assay was developed, so data were not collected.

A participant's serum sample was considered positive for antibodies against cixutumumab if it exhibited a post-treatment antibody level that exceeded the positive upper cut point determined from the anti-cixutumumab level seen in healthy untreated individuals. A participant was considered to have an anti-cixutumumab response if there were 2 consecutive positive samples or if the final sample tested was positive.

Time frame: Predose, immediately prior to the first Cycle 3 and Cycle 5 infusions (3-week cycle) and 30 days after last dose of study drug

Population: Zero participants were analyzed. No assay was available to assess serum anti-cixutumumab antibodies.

TTP is defined as the time from the date of first dose of study drug until the date of objective disease progression. Participants without PD were censored at the time of the last objective tumor assessment. Participants who did not progress and lost to follow-up were censored at the date of the last objective tumor assessment before loss to follow-up. Participants who began new anticancer therapy prior to PD or death were censored at date of last tumor assessment prior to new therapy. Participants who died or had PD after ≥2 missed tumor assessments were censored at date of last tumor assessment prior to the missed assessments.

Time frame: Date of first dose of study drug to date of PD up to 12 months

Population: All randomized participants in Cohort 2 who received any amount of study drug, per the protocol efficacy analysis was only performed for Cohort 2. Participants censored = 14.