Richard Kim, MD, Highlights the Rationale for Assessing Pembrolizumab Plus Standard Chemo in Metastatic MSS/pMMR CRC

During the 2022 American Society of Clinical Oncology Annual Meeting, Richard Kim, MD, discusses the rationale for the phase 1b KEYNOTE-651 trial examining pembrolizumab plus chemotherapy in metastatic colorectal cancer.

In an interview with CancerNetwork® during the 2022 American Society of Clinical Oncology Annual Meeting, Richard Kim, MD, service chief of Medical Gastrointestinal Oncology and senior member in the Gastrointestinal Oncology Department at Moffitt Cancer Center in Tampa, Florida, described the rationale for the phase 1b KEYNOTE-651 trial (NCT03374254) assessing pembrolizumab (Keytruda) in combination with leucovorin and fluorouracil plus either irinotecan or oxaliplatin in microsatellite-stable (MSS) or mismatch repair (MMR) proficient metastatic colorectal cancer.


We know that immunotherapy is [a modality] that has been successful in other diseases. In colon cancer, unfortunately, immunotherapy only works in 5% of patients. [That] set of patients have MMR [mismatch repair] deficient, MSI [microsatellite instability] high, or POLE mutation[–positive tumors]. Therefore, the other 95% of the patient are MSS, which we call a cold tumor. The goal of the trial was to convert those cold tumors to hot tumors by adding targeted agents or chemotherapy to immunotherapy to change the microenvironment, so the immunotherapy in those situations may work better.


Kim RD, Tehfe M, Kavan P, et al. Pembrolizumab (pembro) plus mFOLFOX7 or FOLFIRI for metastatic colorectal cancer (CRC) in KEYNOTE-651: Long-term follow-up of cohorts B and D. J Clin Oncol. 2022;40(suppl 16):3521. doi:10.1200/JCO.2022.40.16_suppl.3521

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