PMV Pharmaceuticals, Inc. announced updated Phase 1 results from its ongoing Phase 1/2 PYNNACLE clinical trial that showed PC14586 achieved efficacy in heavily pretreated patients across multiple tumor types and was well tolerated with a favorable safety profile. Results are being presented in a late-breaking poster session by Alison M. Schram, M.D., Medical Oncologist at Memorial Sloan Kettering Cancer Center and PYNNACLE Study Investigator, at the 2023 AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics taking place in Boston, Massachusetts. Study highlights include: Patient Characteristics: As of the September 5, 2023 data cutoff, 67 safety evaluable patients were treated in the efficacious dose range (1150 mg daily and above).

Median age was 63 years (32-84); 61% of patients were female. Median number of prior lines of systemic therapy was three (range: 1-9). Efficacy:Confirmed responses were observed in patients whose tumors were TP53 Y220C and KRAS wild-type in the efficacious dose range, in multiple tumor types including ovarian, breast, prostate, small-cell lung, and endometrial cancer.

Median duration of response was seven months. Overall response rate (ORR) per RECIST version 1.1 was 38% (6/16 evaluable patients) at the Recommended Phase 2 Dose (RP2D) of 2000 mg daily and 34% (13/38) in the efficacious dose range. Safety: Treatment-related adverse events (TRAEs) were mostly Grade 1-2 with the most frequent TRAEs observed (>20%) being nausea, vomiting and blood creatinine increased, with a low rate of discontinuations due to a TRAE (3%).

Gastrointestinal toxicity improved when PC14586 was administered with food. Phase 2 Plans: A RP2D of 2000 mg once daily was selected based on overall safety, pharmacokinetics (PK), and efficacy in alignment with the U.S. Food and Drug Administration at an End of Phase 1 meeting held in third quarter 2023. The planned Phase 2 patient population includes TP53 Y220C and KRAS wild-type patients.

PMV plans to initiate a registrational Phase 2 trial in early 2024.