NEW YORK – PMV Pharmaceuticals on Wednesday said it dosed the first patient in a Phase II study of its p53 reactivator rezatapopt in patients with wild-type KRAS tumors harboring a tp53 Y220C mutation.
In the PYNNACLE Phase I/II trial, PMV researchers are evaluating the safety, tolerability, and efficacy of rezatapopt alone and in combination with Merck's Keytruda (pembrolizumab) as a treatment for patients with advanced solid tumors. PMV partnered with Merck in 2022 to study rezatapopt (formerly PC14586) with Keytruda.
To be eligible for the trial, the patient must have a tumor that tests positive for the tp53 Y220C mutation and have been previously treated with one or more lines of anticancer therapy. In the Phase I portion of the trial, the investigators sought to establish a maximum tolerated dose and a recommended Phase II dose for rezatapopt. They also evaluated measures of safety and tolerability and assessed preliminary efficacy.
New York-based PMV presented Phase I results from the trial last week demonstrating anti-tumor activity for rezatapopt in heavily pretreated patients with tp53 Y220C-mutated ovarian cancer. Seven out of 10 treated patients had a confirmed partial response, seven had stable disease, and one patient had progressive disease. The median duration of response was seven months. Treatment-related adverse events among patients in the efficacious dose range were mostly grade 1 and 2, primarily nausea, vomiting, and increased blood creatinine.
In the Phase II portion of the trial, PMV will now evaluate overall response rate in 114 patients with ovarian, lung, breast, and endometrial cancers, as well as other solid tumors treated with rezatapopt at 2,000 mg once daily as a monotherapy in patients. The investigators will also track secondary efficacy endpoints including progression-free survival, disease control rate, overall survival, and duration of response.
In January, PMV laid off 30 percent of its workforce in a corporate restructuring to prioritize development of rezatapopt.