Prelude Therapeutics and Merck & Co (MSD) have collaborated to evaluate PRT3789 in combination with Keytruda (pembrolizumab) in a Phase II trial for the treatment of SMARCA4-mutated cancers.

Keytruda is an anti-PD-1 therapy of MSD.

Under the agreement, MSD will supply Keytruda for the combination trial, with Prelude acting as the sponsor. Both companies retain commercial rights to their respective compounds.

Prelude president and chief medical officer Jane Huang said: “Through this collaboration of potentially complementary mechanisms, we may have the potential to positively impact clinical outcomes in patients harbouring a SMARCA4 mutation, who have previously been known to have limited treatment options.”

The Phase II clinical study aims to assess the investigational SMARCA2 degrader alongside MSD's anti-PD-1 therapy.

PRT3789 is currently in Phase I clinical development, targeting biomarker-selected patients with SMARCA4 mutations.

Prelude is planning to complete the monotherapy dose escalation by mid-2024 and determine the recommended Phase II dose.

Additional enrolments for patients with NSCLC and SMARCA4 loss-of-function mutations are underway.

The study’s objectives include establishing the tolerability and safety profile of PRT3789, evaluating its activity, pharmacokinetics, and pharmacodynamics, and identifying indications for progression to a registrational trial.

Preclinical models have shown that combining a SMARCA2 degrader with an anti-PD-1 monoclonal antibody in SMARCA4-mutated cancers can enhance anti-tumour immunity and show tumour regressions.

In addition to PRT3789, Prelude is developing other targeted therapies, including a potent and selective CDK9 inhibitor, PRT2527, and a next-generation CDK4/6 inhibitor, PRT3645.

The company is also working on an orally bioavailable SMARCA2 degrader, PRT7732, and has partnered with AbCellera to discover and develop up to five precision antibody-drug conjugates together.

In May this year, MSD reported that its Phase III KEYNOTE-522 clinical trial of Keytruda to treat high-risk, early-stage, triple-negative breast cancer (TNBC) met its overall survival (OS) endpoint.