PMV Pharma Reports Promising Phase 2 Results in TP53-Mutated Cancers
PMV Pharmaceuticals has announced encouraging interim findings from the phase 2 portion of its PYNNACLE trial, which is evaluating rezatapopt monotherapy in patients with advanced solid tumours carrying the TP53 Y220C mutation.
The therapy, designed to restore the function of the tumour-suppressing p53 protein, demonstrated clinically meaningful responses across a wide range of hard-to-treat cancers.
Broad Efficacy Across Multiple Tumour Types
Among 97 evaluable patients, the overall response rate (ORR) was reported at 33%, with a median duration of response of 6.2 months. Confirmed responses were seen across eight tumour types, including ovarian, lung, breast, endometrial, head and neck, colorectal, gallbladder, and ampullary carcinoma.
The strongest efficacy was observed in ovarian cancer patients, where the ORR reached 43% among 44 participants. This included one complete response and 17 confirmed partial responses, with a median duration of response extending to 7.6 months.
Endometrial cancer patients demonstrated a remarkable 60% ORR, while lung and breast cancer cohorts reported 22% and 18% respectively. For other solid tumours, the ORR stood at 21%.
Safety and Tolerability
Safety data from 109 patients reinforced rezatapopt’s favourable profile.
Most treatment-related adverse events were graded as mild (Grade 1–2), with Grade 3 events occurring in fewer than 6% of patients and resolving while treatment continued. Importantly, no discontinuations were reported due to liver enzyme elevations.
The therapy was also found to be better tolerated when administered with food, improving gastrointestinal outcomes compared with earlier phase 1 data. Laboratory abnormalities were largely transient and reversible, and the overall discontinuation rate due to adverse events was just 3.7%.
Next Steps and Regulatory Outlook
Following discussions with the US Food and Drug Administration, PMV Pharma plans to expand the study by enrolling an additional 20–25 platinum-resistant or refractory ovarian cancer patients by the first quarter of 2026.
Looking further ahead, the company expects to file a New Drug Application (NDA) in Q1 2027, marking a significant step towards potential regulatory approval.
The Chief Development Officer at PMV Pharma, emphasised the importance of the findings, stating that the interim phase 2 data demonstrate rezatapopt’s potential as a first-in-class therapy capable of harnessing the power of p53 to address cancers with high unmet need.
Conclusion
The PYNNACLE trial’s interim results suggest that rezatapopt could represent a breakthrough in the treatment of TP53 Y220C-mutated cancers, with robust efficacy signals across multiple tumour types and a manageable safety profile.
With further enrolment planned and an NDA on the horizon, PMV Pharma’s candidate is steadily moving closer to becoming a much-needed therapeutic option for patients facing some of the most challenging forms of cancer.
News Credits: Rezatapopt shows promise in phase 2 trial for TP53 Y220C solid tumours
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