Phase 2 study of pembrolizumab-based combination therapy in patients with microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR) stage IV colorectal cancer (CRC). (ASCO 2022)
This ongoing, open-label, multicenter, multiarm, randomized, phase 2 trial (NCT04895722) will evaluate efficacy and safety of coformulated pembro and anti–CTLA-4 quavonlimab compared with pembro monotherapy in chemotherapy-refractory stage IV dMMR/MSI-H CRC in cohort A; the study will also evaluate the efficacy and safety of 4 pembro-based combinations (coformulation of pembro with either quavonlimab, anti–LAG-3 favezelimab, or anti-TIGIT vibostolimab; anti-ILT4 MK-4830 given sequentially with pembro) compared with pembro monotherapy in previously untreated stage IV dMMR/MSI-H CRC in cohort B. Pts aged ≥18 y with histologically confirmed stage IV dMMR/MSI-H CRC who have measurable disease per RECIST v1.1 by investigator and confirmed by blinded independent central review (BICR), will be enrolled. Pts in cohort A must have experienced PD after fluoropyrimidine, irinotecan, and oxaliplatin, with or without anti-VEGF antibody, and anti-EGFR antibody for pts with left-sided tumors that are RAS WT...For both cohorts, primary end point is ORR by BICR per RECIST v1.1; secondary end points are ORR assessed by investigator, DOR and PFS assessed by BICR and by investigator per RECIST v1.1, OS, and safety and tolerability graded per NCI CTCAE v5.0. Enrollment in this trial is ongoing.