KEYSTEP-008: phase II trial of pembrolizumab-based combination in MSI-H/dMMR metastatic colorectal cancer

André T., Pietrantonio F., Avallone A., Gumus M., Wyrwicz L., Kim J. G., ...More

Future Oncology, vol.19, no.37, pp.2445-2452, 2023 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Review
  • Volume: 19 Issue: 37
  • Publication Date: 2023
  • Doi Number: 10.2217/fon-2022-1105
  • Journal Name: Future Oncology
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, CINAHL, EMBASE, MEDLINE
  • Page Numbers: pp.2445-2452
  • Keywords: favezelimab, MK-4830, MSI-H/dMMR colorectal cancer, pembrolizumab, quavonlimab, vibostolimab
  • Hacettepe University Affiliated: Yes

Abstract

Robust clinical activity has been observed with the immune checkpoint inhibitor pembrolizumab in patients with microsatellite instability-high/mismatch repair-deficient (MSI-H/dMMR) metastatic colorectal cancer (mCRC). However, given the response rate of 45% and a median progression-free survival of 16.5 months with first-line pembrolizumab demonstrated in KEYNOTE-177, there is room for improvement. Targeting a second immune receptor, such as CTLA-4, LAG-3, TIGIT, or ILT-4 may improve efficacy of PD-1 inhibition. Here we describe the design and rationale for the open-label, randomized, phase II KEYSTEP-008 trial, which will evaluate the efficacy and safety of pembrolizumab-based combination therapy compared with pembrolizumab monotherapy in chemotherapy-refractory (cohort A) or previously untreated (cohort B) MSI-H/dMMR mCRC.