KEYNOTE-164: Phase II study of pembrolizumab (MK-3475) for patients with previously treated, microsatellite instability-high advanced colorectal carcinoma.

TPS787

Background: A subset of advanced colorectal cancers (CRC) is characterized by mismatch repair (MMR) deficiency leading to a microsatellite instability-high (MSI-H) phenotype, which is characterized by a high mutational burden and lymphocytic infiltrates. Pembrolizumab is a monoclonal anti–PD-1 antibody designed to block the interaction between PD-1 and its ligands PD-L1 and PD-L2. In the phase II KEYNOTE-016 study, pembrolizumab provided an ORR of 62% in patients (pts) with progressive MMR-deficient metastatic CRC vs 0% in pts with MMR-proficient CRC. The multicenter, phase II KEYNOTE-164 trial (NCT02460198) will evaluate the efficacy and safety of pembrolizumab in pts with previously treated, advanced MSI-H CRC. Methods: Key eligibility criteria include age ≥ 18 y; advanced CRC; MSI-H phenotype evidenced by ≥ 2 allelic shifts using a PCR-based assay or lack of expression of ≥ 1 MMR protein (MLH1, MSH2, MSH6, PMS2) by IHC; prior treatment with a fluoropyrimidine, oxaliplatin, irinotecan, bevacizumab, and, if KRAS and NRAS wild type, cetuximab or panitumumab; ECOG PS 0-1; no active autoimmune disease or brain metastases; and no prior anticancer therapy within 2 wk of study treatment. Pembrolizumab 200 mg Q3W will be administered for 35 cycles or until disease progression, unacceptable toxicity, pt withdrawal, or investigator decision. Clinically stable pts with RECIST-defined progression may continue pembrolizumab until a scan performed ≥ 4 wk later confirms progression. Pts who complete all 35 cycles or who discontinue pembrolizumab following a complete response and experience progression may be eligible for 1 y of pembrolizumab retreatment. Response will be evaluated every 9 wk per RECIST v1.1 by central review and per RECIST adapted for immunotherapy response patterns. AEs will be assessed throughout treatment and for 30 d thereafter (up to 90 d for serious AEs) and graded per NCI CTCAE v4.0. Pts will be followed for survival every 2 mo. ORR per RECIST v1.1 by central review is the primary end point; secondary end points include PFS, OS, disease control rate, and duration of response. Enrollment is ongoing and will continue until ~60 pts have enrolled. Clinical trial information: NCT02460198.