Abstract 493P
Background
Pembro, a PD-1 inhibitor, has limited efficacy in microsatellite stable (MSS)/mismatch repair-proficient (pMMR) mCRC. The phase Ib KEYNOTE-651 study (NCT03374254) evaluated pembro + mFOLFOX7 (cohort B) or FOLFIRI (cohort D) in pts with MSS/pMMR mCRC. Updated results with more pts and additional follow-up are presented.
Methods
Pts were ≥18 y with MSS/pMMR mCRC and no prior systemic chemotherapy (cohort B) or 1 prior fluoropyrimidine + oxaliplatin–based regimen (cohort D). Pts received pembro 200 mg Q3W + mFOLFOX7 (oxaliplatin, 85 mg/m2; leucovorin, 400 mg/m2; 5-FU, 2400 mg/m2) Q2W (cohort B) or pembro 200 mg Q3W + FOLFIRI (irinotecan, 180 mg/m2; leucovorin, 400 mg/m2; 5-FU, 2400 mg/m2) Q2W (cohort D). Each cohort comprised 2 phases: dose finding (part 1) and dose confirmation (part 2). Primary end points: safety/tolerability and recommended phase II dose (RP2D). Secondary end point: ORR by investigator assessment. Data are presented for parts 1 and 2 combined.
Results
31 pts in cohort B and 32 pts in cohort D received treatment; median (range) follow-up was 41.9 mo (13.3-101.9) in cohort B and 43.0 mo (5.3-100.0) in cohort D. Treatment was discontinued in 19 pts (61%) in cohort B and 20 pts (63%) in cohort D, mostly due to PD (cohort B: n=11, 36%; cohort D: n=14, 44%). There was 1 dose-limiting toxicity (grade 3 small-intestine obstruction) in cohort D. RP2D was defined as the starting dose level for both cohorts. All pts had ≥1 treatment-related adverse event (TRAE). Grade ≥3 TRAEs occurred in 18 pts (58%) in cohort B and 17 pts (53%) in cohort D. Most common TRAEs: neutrophil count decreased (23%) in cohort B and neutropenia and diarrhea (13% each) in cohort D. There were no grade 5 TRAEs. Confirmed ORR was observed in 18 pts (58%; 1 CR, 17 PRs) and 5 pts (16%; 5 PRs) in cohorts B and D, respectively; disease control rate was 94% and 63%, respectively. Median (range) duration of response was 10.3 mo (3.5+ to 18.5+) in cohort B and 17.4 mo (1.6+ to 20.2) in cohort D.
Conclusions
Pembro + mFOLFOX7 or FOLFIRI was safe and tolerable in pts with MSS/pMMR mCRC. Preliminary evidence of efficacy was seen in both cohorts.
Clinical trial identification
NCT03374254.
Editorial acknowledgement
Medical writing and/or editorial assistance was provided by Matthew Grzywacz, PhD, of the ApotheCom pembrolizumab team (Yardley, PA, USA) and was funded by Merck Sharp & Dohme Corp.
Legal entity responsible for the study
Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.
Funding
Funding for this research was provided by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, and Array BioPharma.
Disclosure
R. Kim: Advisory/Consultancy, Research grant/Funding (self): BMS; Advisory/Consultancy, Speaker Bureau/Expert testimony: Lilly; Advisory/Consultancy, Research grant/Funding (self): Bayer; Research grant/Funding (self): Eisai. P. Kavan: Advisory/Consultancy, Research grant/Funding (institution): Merck. M. Fakih: Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Amgen; Advisory/Consultancy: Pfizer; Advisory/Consultancy: Array; Advisory/Consultancy: Bayer; Speaker Bureau/Expert testimony: Guardant360; Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): Novartis. J.S. Kortmansky: Research grant/Funding (institution): Merck; Research grant/Funding (institution): Roche. L. Wong: Research grant/Funding (institution): Merck. M. Tehfe: Honoraria (self), Advisory/Consultancy: Merck. J.J. Li: Shareholder/Stockholder/Stock options, Full/Part-time employment: Merck & Co., Inc. A.D. Eyring, C. Mayo: Full/Part-time employment: Merck & Co., Inc. E.G. Chiorean: Advisory/Consultancy: Celgene; Advisory/Consultancy: Array; Advisory/Consultancy: Legend Biotech; Advisory/Consultancy: Ipsen; Research grant/Funding (self): Merck; Research grant/Funding (self): Roche; Research grant/Funding (self): Stemline; Research grant/Funding (self): MacroGenics; Research grant/Funding (self): Boehringer-Ingelheim; Research grant/Funding (self): Halozyme ; Research grant/Funding (self): Clovis; Research grant/Funding (self): Fibrogen; Research grant/Funding (self): Rafael. All other authors have declared no conflicts of interest.