MEN1611 With Cetuximab in Metastatic Colorectal Cancer (C-PRECISE-01)

The best ORR was defined as percentage of participants who had a best overall response to therapy of complete response (CR), partial response (PR), stable disease (SD), or progressive disease (PD) and was defined according to Response Evaluation Criteria in Solid Tumors version 1.1 assessment locally performed using computed tomography scans or magnetic resonance imaging of the chest and abdomen (including pelvis and adrenal glands).

Time frame: Up to 37 Months

Population: Efficacy Population: all participants who received at least 2 complete treatment cycles and had at least 1 disease assessment.

A DLT was defined as any of the following adverse drug reactions (ADRs) related to the combination regimens or to MEN1611 alone and unrelated to the participants' underlying disease or concomitant medication occurring during Cycle 1 over the DLT assessment window of 28 days: any Grade 3 (lasting \>7 days) or Grade 4 increase in aspartate aminotransferase, alanine aminotransferase, or alkaline phosphatase; any Grade ≥3 cardiac disorder or new segmental wall-motion abnormalities; any Grade ≥3 non-hematologic toxicity with the following exceptions: nausea, vomiting, diarrhea, skin rash, hyperglycemia. An ADR was defined as any adverse event suspected by the investigator and/or the sponsor to be related to MEN1611, cetuximab, or both given in combination.

Time frame: Day 1 through Day 28 of Cycle 1 (28 days/cycle)

Population: Dose-limiting Toxicity (DLT) Population: all participants who received at least 80% of MEN1611 and 75% of cetuximab during Cycle 1 with a safety follow-up of 28 days after the first administration of the study treatment. Any participant who experienced DLT was also considered evaluable, regardless of the dose received. As pre-specified, data were collected and reported for the 'Phase 1b (Dose Confirmation)' cohort only.

RP2D was defined as the highest dose level in milligrams (mg) at which no more than 1 participant during the dose confirmation phase (Phase 1b) experienced a dose-limiting toxicity (DLT) during the DLT assessment window (28 days), or the maximum dose judged to be tolerable by the data safety committee.

Time frame: Day 1 through Day 28 of Cycle 1 (28 days/cycle)

Population: Safety Population: all participants who received at least 1 dose of MEN1611. As pre-specified, RP2D data were collected and are reported for 'Phase 1b (Dose Confirmation)' cohort only.

DCR was defined as percentage of participants whose disease shrank or remained stable over a certain time period and was calculated based on the sum of the CR, PR, and SD rates according to local assessment.

Time frame: Up to 37 Months

Population: Efficacy Population: all participants who received at least 2 complete treatment cycles and had at least 1 disease assessment.

DOR was defined as the time from confirmation of a PR, CR or SD as locally assessed, until the disease had been shown to progress following treatment. Participants with a previous response who did not show a relapse or died without recording a relapse were censored at their last available relapse-free tumor assessment date. Participants with only one tumor assessment after baseline showing a PD were not included in the calculation.

Time frame: Up to 37 months

Population: Efficacy Population: all participants who received at least 2 complete treatment cycles and had at least 1 disease assessment. Here, 'Overall Number of Participants Analyzed' signifies those participants who were evaluable for this outcome measure.

OS was defined as the number of days between the first study treatment administration and death from any cause. Participants still alive that had withdrawn from the study were censored using the latest among end of study and follow-up dates. Drop-out participants were considered censored and the last available date in which the participant was known to be alive was considered.

Time frame: Up to 37 months

Population: Efficacy Population: all participants who received at least 2 complete treatment cycles and had at least 1 disease assessment.

Blood samples were taken for the analyses of MEN1611 in plasma at designated time points. Results are reported as nanograms/millilitre (ng/mL).

Time frame: Day 22 (1.5 hours postdose) of Cycle 1 (28 days/cycle)

Population: Pharmacokinetics (PK) Set: all participants who received MEN1611 and for whom a PK sample was obtained and analyzed. Here, 'Overall Number of Participants Analyzed' signifies those participants who were evaluable for this outcome measure.

PFS was defined as the number of days between the first study treatment administration to the date of first documented disease progression as per local assessment, relapse or death from any cause. Responding participants and participants who were lost to follow-up were censored at their last tumor assessment date.

Time frame: Up to 37 months

Population: Efficacy Population: all participants who received at least 2 complete treatment cycles and had at least 1 disease assessment.