Pucotenlimab in patients with advanced mismatch repair-deficient or microsatellite instability-high solid tumors: A multicenter phase 2 study

Cell Rep Med. 2023 Dec 19;4(12):101301. doi: 10.1016/j.xcrm.2023.101301. Epub 2023 Nov 27.

Abstract

We report a multicenter, phase 2 study evaluating the efficacy of pucotenlimab, an anti-PD-1 antibody, in patients with mismatch repair-deficient (dMMR) or microsatellite instability-high (MSI-H) tumors, and potential biomarkers for response. Overall, 100 patients with previously treated, advanced solid tumors centrally confirmed as dMMR or MSI-H received pucotenlimab at 200 mg every 3 weeks. The most common cancer type is colorectal cancer (n = 71). With a median follow-up of 22.5 months, the objective response rate is 49.0% (95% confidence interval 38.86%-59.20%) as assessed by the independent review committee, while the median progression-free survival and overall survival have not been reached. Grade ≥3 treatment-related adverse events were observed in 18 patients. For the biomarker analysis, responders are enriched in patients with mutations in the KMT2D gene. Pucotenlimab is an effective treatment option for previously treated advanced dMMR/MSI-H solid tumors, and the predictive value of KMT2D mutation warrants further research. This study is registered with ClinicalTrials.gov: NCT03704246.

Keywords: biomarker; efficacy; microsatellite instability-high; mismatch repair deficient; safety; solid tumor.

Publication types

  • Multicenter Study
  • Clinical Trial, Phase II
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Brain Neoplasms
  • Colorectal Neoplasms* / drug therapy
  • Colorectal Neoplasms* / genetics
  • DNA Mismatch Repair / genetics
  • Humans
  • Microsatellite Instability*
  • Neoplastic Syndromes, Hereditary
  • Treatment Outcome

Supplementary concepts

  • Turcot syndrome

Associated data

  • ClinicalTrials.gov/NCT03704246