Study of PC14586 rezatapopt Alone or With Pembrolizumab in Advanced Solid Tumors With TP53 Y220C Mutation

What this Trial Is About

Researchers are evaluating the safety, tolerability, pharmacokinetics, and effectiveness of PC14586 rezatapopt, an oral small molecule that reactivates the p53 protein selectively for the TP53 Y220C mutation. This Phase 12 open-label study includes patients with locally advanced or metastatic solid tumors harboring this mutation. The study aims to find the best dose, assess treatment response rates, and monitor quality of life in various cancer types, including ovarian, lung, breast, and endometrial cancers. The study consists of multiple parts Phase 1 monotherapy dose escalation to find the maximum tolerated dose and recommended Phase 2 dose RP2D of rezatapopt Phase 1b combination therapy evaluating rezatapopt with pembrolizumab and Phase 2 dose expansion cohorts where participants receive daily oral rezatapopt at the RP2D, either alone or combined with pembrolizumab. Participants receive pembrolizumab intravenously every three weeks when in the combination group, and rezatapopt is taken daily with food. Participants will undergo regular monitoring including safety assessments, blood tests to study drug levels, and imaging scans to measure tumor response using RECIST criteria. Researchers will track adverse events, response rates, progression-free survival, overall survival, and quality of life over several months. The total study duration varies by phase but includes up to 34 months of treatment for Phase 2 and ongoing follow-up for safety and efficacy evaluation.

The Evaluation of PC14586 in Patients With Advanced Solid Tumors Harboring a TP53 Y220C Mutation (PYNNACLE)