PMV Pharmaceuticals announces updated rezatapopt monotherapy interim data

PMV Pharmaceuticals (PMVP) announced updated data from the Phase 2 pivotal portion of the ongoing PYNNACLE clinical trial. Results were presented in an oral presentation by Alison M. Schram, M.D., Medical Oncologist at Memorial Sloan Kettering Cancer Center and PYNNACLE Study Investigator, at the 2025 AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics taking place in Boston, Massachusetts. The ongoing Phase 1/2 PYNNACLE clinical trial is evaluating rezatapopt in patients with advanced solid tumors harboring a TP53 Y220C mutation. The Phase 2 clinical trial data below are summarized as of a September 4, 2025 data cutoff date: The safety population consisted of 112 patients treated with at least one dose of rezatapopt 2000mg daily as monotherapy. Median number of prior lines of systemic therapy was three/ The efficacy population consisted of 103 patients treated with at least one dose of rezatapopt as of the data cutoff date and either had greater than or equal to1 post-baseline tumor assessment or discontinued early. Efficacy: Confirmed responses were observed in patients whose tumors were TP53 Y220C mutated and KRAS wild-type in eight tumor types including ovarian, lung, breast, endometrial, head and neck, colorectal, gallbladder cancers, and ampullary carcinoma. Overall response rate of 34% per investigator assessment according to Response Evaluation Criteria in Solid Tumors version 1.1, including confirmed and unconfirmed responses. The cohort-specific ORRs were as follows: Ovarian cancer: 46% ORR; Breast cancer: 17% ORR; Endometrial cancer: 60% ORR; Lung cancer: 21% ORR; Other solid tumors: 21% ORR. Across all cohorts, the median time to response was 1.3 months and the median duration of response was 7.6 months. In the ovarian cancer cohort, the median time to response was 1.3 months and median duration of response was 8.0 months. Post the September 4, 2025 data cutoff date, four uPRs were confirmed and one uPR remains on treatment. Safety: Treatment-related adverse events were mostly Grade 1-2 with the most frequent TRAEs observed being nausea, fatigue, blood creatinine increased, and alanine aminotransferase increased. The rates of individual Grade 3 TRAEs were less than or equal to6%. All Grade 3 TRAEs resolved on treatment and there were no discontinuations due to Grade 3 aspartate aminotransferase/ALT elevations. Rezatapopt administration with food led to an improvement in gastrointestinal tolerability relative to Phase 1 data. Lab abnormalities were manageable, with the majority of cases being transient and reversible. The rate of drug discontinuations due to a TRAE was 3.6%.