PMV Pharma has announced encouraging interim results from the phase 2 portion of its PYNNACLE trial, evaluating rezatapopt monotherapy in patients with advanced solid tumours harbouring a TP53 Y220C mutation.
Confirmed responses were observed across eight tumour types, including ovarian, lung, breast, endometrial, head and neck, colorectal, gallbladder and ampullary carcinoma. Among 97 evaluable patients, the overall response rate (ORR) was 33%, with a median duration of response of 6.2 months.
The ovarian cancer cohort showed the strongest efficacy, with a 43% ORR among 44 patients. This included one complete response and 17 confirmed partial responses. Median duration of response was 7.6 months.
Endometrial cancer patients showed a 60% ORR, while lung cancer and breast cancer cohorts reported 22% and 18% respectively. Other solid tumours demonstrated a 21% ORR.
Safety data from 109 patients indicated that most treatment-related adverse events were Grade 1-2. Grade 3 events occurred in fewer than 6% of cases and resolved on treatment. No discontinuations were reported due to liver enzyme elevations.
Rezatapopt was better tolerated when administered with food, improving gastrointestinal outcomes compared to phase 1 data. Lab abnormalities were mostly transient and reversible, with a 3.7% discontinuation rate due to adverse events.
Following feedback from the US FDA, PMV Pharma plans to enrol an additional 20–25 platinum resistant/refractory ovarian cancer patients by Q1 2026. A New Drug Application is expected in Q1 2027.
Dr Deepika Jalota, Chief Development Officer, said: “These phase 2 PYNNACLE interim trial data illustrate that rezatapopt, a first-in-class therapy, has the potential to harness the power of p53 to address cancers with high unmet need.”
