Rezatapopt shows responses

Cancer cells often disable p53, a protein that acts like a brake on damaged cells. Rezatapopt is a pill designed to fit a specific flaw in that brake — the TP53 Y220C mutation — and researchers reported tumor shrinkage in 44.4% of evaluable ovarian cancer patients at the Society of Gynecologic Oncology meeting in San Juan on April 12, 2026. (onclive.com, sgo.org) The data came from the phase 2 PYNNACLE trial, a global basket study of patients with advanced solid tumors carrying TP53 Y220C and wild-type KRAS. In the ovarian cohort, 72 patients were evaluable, and the reported objective response rate was 44.4%, including a 1.4% complete response rate and a 43.1% partial response rate. (onclive.com) Investigators said the median duration of response was 8.2 months, and the social post describing the presentation said responses appeared quickly and safety was manageable. OncLive reported stable disease in 31.9% of evaluable patients and progressive disease in 6.9%. (onclive.com, x.com) Ovarian cancer is a logical place to test this drug because TP53 is mutated in much of high-grade serous disease, and the Y220C subtype appears in about 3% of ovarian cancers and more than 3% of high-grade serous ovarian cancers. Rezatapopt is built to bind the pocket created by that mutation and hold the misshapen p53 protein in a more normal, working form. (cor2ed.com, nejm.org) The ovarian patients in this analysis were heavily pretreated, with a median of four prior lines of therapy. OncLive reported that 61% had platinum-resistant disease and 36% had platinum-refractory disease, two settings where treatment options are limited and remissions are often short. (onclive.com) Activity also appeared across subgroups that matter in current ovarian cancer care. OncLive reported a 52.6% response rate after prior poly(ADP-ribose) polymerase inhibitor treatment, plus similar activity in folate receptor alpha-positive disease at 50.0% and folate receptor alpha-negative disease at 41.9%. (onclive.com) The safety picture has been fairly consistent across studies of the drug. In the phase 1 study published in The New England Journal of Medicine, the recommended phase 2 dose was 2,000 milligrams once daily with food, the most common side effects included nausea, vomiting, higher creatinine, fatigue, and anemia, and 3% of patients stopped treatment because of a treatment-related adverse event. (nejm.org) This ovarian update builds on earlier PYNNACLE data PMV Pharmaceuticals released on October 24, 2025. At that cutoff, the company reported a 46% response rate in 48 evaluable ovarian cancer patients, an 8.0-month median duration of response, and a plan to seek a New Drug Application in the first quarter of 2027 for platinum-resistant or platinum-refractory ovarian cancer. (finance.yahoo.com) The next test is whether these conference results hold up with longer follow-up and regulatory review. For now, the drug’s pitch is simple: find the small subset of ovarian tumors with TP53 Y220C, and try to switch p53’s brake back on. (nejm.org, finance.yahoo.com)