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Pucotenlimab in patients with advanced mismatch repair-deficient or microsatellite instability-high solid tumors: A
Bo Zhang1, Yan Song1, Suxia Luo2
1Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
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.
Insights
Pucotenlimab shows significant efficacy in treating advanced solid tumors with mismatch repair-deficiency (dMMR) or microsatellite instability-high (MSI-H) biomarkers. KMT2D gene mutations may predict patient response to this immunotherapy.
Area of Science:
- Oncology
- Immunotherapy
- Genetics
Background:
- Mismatch repair-deficient (dMMR) or microsatellite instability-high (MSI-H) solid tumors represent a distinct subset of cancers.
- Immunotherapy targeting the PD-1 pathway has shown promise in various malignancies.
- Identifying predictive biomarkers is crucial for optimizing treatment strategies.
Purpose of the Study:
- To evaluate the efficacy and safety of pucotenlimab, an anti-PD-1 antibody, in patients with advanced dMMR/MSI-H solid tumors.
- To explore potential biomarkers, including KMT2D gene mutations, associated with treatment response.
- To assess the overall response rate (ORR) and survival outcomes.
Main Methods:
- A multicenter, phase 2 clinical trial was conducted.
- 100 patients with previously treated, advanced dMMR/MSI-H solid tumors received pucotenlimab (200 mg every 3 weeks).
- Objective response rate (ORR) was assessed by an independent review committee; biomarker analysis included KMT2D mutation status.
Main Results:
- The objective response rate (ORR) was 49.0% (95% CI 38.86%-59.20%) with a median follow-up of 22.5 months.
- Median progression-free survival (PFS) and overall survival (OS) were not reached.
- Grade ≥3 treatment-related adverse events occurred in 18 patients; responders were enriched in those with KMT2D mutations.
Conclusions:
- Pucotenlimab demonstrates significant efficacy as a treatment option for advanced dMMR/MSI-H solid tumors.
- KMT2D gene mutations show potential as a predictive biomarker for pucotenlimab response.
- Further research into KMT2D's predictive value is warranted for personalized immunotherapy.
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