Prelude Therapeutics and Merck to Test PRT3789 with KEYTRUDA® in SMARCA4-Mutated Cancer Patients

Prelude Therapeutics Incorporated, a clinical-stage company specializing in precision oncology, has formally announced its collaboration with Merck & Co. This partnership aims to conduct a Phase 2 clinical trial that will combine Prelude’s investigational SMARCA2 degrader, PRT3789, with Merck’s anti-PD-1 therapy, KEYTRUDA® (pembrolizumab), targeting patients with cancers that harbor SMARCA4 mutations.

The collaboration between Prelude and Merck brings together two potentially complementary mechanisms of action. Prelude's President and Chief Medical Officer, Dr. Jane Huang, expressed enthusiasm about the partnership, highlighting the potential to enhance clinical outcomes for patients with limited treatment options due to SMARCA4 mutations.

PRT3789 is recognized for its potent, highly selective qualities as a first-in-class SMARCA2 degrader. Currently in Phase 1 clinical development, PRT3789 is being tested on patients with SMARCA4 mutant biomarkers. Prelude anticipates completing the monotherapy dose escalation by mid-2024 and aims to determine the recommended Phase 2 dose. Additionally, the company is enrolling patients into backfill cohorts that are enriched for non-small cell lung cancer (NSCLC) and SMARCA4 loss-of-function mutations. The objectives of this Phase 1 study are to confirm the safety and tolerability of PRT3789 both as a standalone treatment and in combination with docetaxel, as well as to evaluate its activity, pharmacokinetics, and pharmacodynamics. The study will also help determine the dose and potential indications for future registrational clinical trials.

The combination of SMARCA2 degrader and an anti-PD-1 monoclonal antibody (mAb) is supported by pre-clinical data and mechanistic rationale that were presented at the 2023 AACR International Conference on Molecular Targets and Cancer Therapeutics. In pre-clinical models, the combination demonstrated enhanced anti-tumor immunity and significant tumor regressions in cancers with SMARCA4 mutations.

Under the agreement terms, Merck will supply KEYTRUDA for the Phase 2 clinical combination trial, while Prelude will act as the trial sponsor. Both companies will retain all commercial rights to their respective compounds, whether used as monotherapies or in combination therapies.

The collaboration underscores Prelude Therapeutics' commitment to advancing its pipeline of innovative drug candidates aimed at critical cancer cell pathways. The company's pipeline includes multiple candidates, such as PRT2527, a selective CDK9 inhibitor, and PRT3645, a next-generation CDK4/6 inhibitor. Additionally, Prelude is developing PRT7732, an orally bioavailable SMARCA2 degrader. The company is also engaged in a partnership with AbCellera to jointly develop up to five next-generation antibody-drug conjugate products, leveraging AbCellera’s discovery and development platform along with Prelude’s expertise in medicinal chemistry and drug development.

This strategic move aligns with Prelude's mission to create best-in-class, small molecule compounds that address clinically validated pathways for cancers affecting underserved patient populations. Through collaborations and a robust pipeline, Prelude aims to make significant strides in oncology, offering new hope to patients with challenging cancer types.