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

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.

Graphical abstract

Figure 1

Tumor response in patients with previously treated dMMR/MSI-H solid tumors per RECIST v1.1 based on IRC’s assessment (A) Percentage changes from baseline in the sum of the tumor burden for target lesions over time until first progressive disease (if any). (B) The best percentage changes from baseline in the sum of the tumor burden for target lesions before the first progressive disease (if any). The results of the KMT2D mutational status are also shown in the plot. (C) The swimmer plot showing the key events during the treatment for each patient. The dotted lines in (A) and (B) indicate a 30% reduction or 20% increase.