NEW YORK – PMV Pharmaceuticals on Monday said it will study its investigational therapy PC14586 in combination with Merck's checkpoint inhibitor Keytruda (pembrolizumab) in a Phase I/II trial under a recently inked clinical trial collaboration and supply agreement.
Cranbury, New Jersey-based PMV said it will study the PC14586-Keytruda combination in a new arm of the ongoing PYNNACLE trial. PMV will enroll in the arm 36 patients with advanced solid tumors with the p53 Y220C mutation and assess PC14586-Keytruda's safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy.
PC14586 is designed to selectively bind to the p53 Y220C mutant protein and restore its wild-type tumor-suppressing function. PMV began studying the agent in the PYNNACLE trial in 2020, intending to enroll up to 130 patients with p53 Y220C-mutant advanced cancers. The p53 Y220C mutation is observed in at least 30 different tumor types and accounts for 1.8 percent of all p53 mutations.
The drug, which has fast track status from the US Food and Drug Administration, has already shown preliminary activity as a single agent in PYNNACLE. Other preclinical research has suggested that p53 Y220C reactivators, by increasing the number of T cells in the tumor microenvironment, may have an additive anti-tumor effect when combined with checkpoint inhibitors.
Now, the company has decided to test out this hypothesis. "Our tumor-agnostic study provides compelling scientific rationale for exploring PC14586 in combination with Keytruda in an effort to improve outcomes for more patients," PMV Pharma Chief Medical Officer Leila Alland said in a statement.
PMV Pharma is sponsoring the trial, and Merck is supplying Keytruda for the study. The companies didn't disclose the financial details of the deal.