Prelude Therapeutics Announces Clinical Collaboration with Merck to Evaluate PRT3789 in Combination with KEYTRUDA® (pembrolizumab) in Patients with SMARCA4-Mutated Cancers

Core Viewpoint - Prelude Therapeutics has entered into a collaboration with Merck to conduct a Phase 2 clinical trial evaluating the combination of its investigational SMARCA2 degrader, PRT3789, with Merck's anti-PD-1 therapy, KEYTRUDA, targeting patients with SMARCA4-mutated cancers [2][4][7]. Group 1: Clinical Development - PRT3789 is a first-in-class, highly selective SMARCA2 degrader currently in Phase 1 clinical development, focusing on biomarker-selected SMARCA4 mutant patients [3][11]. - The Phase 1 study aims to establish the safety and tolerability of PRT3789, evaluate its activity, pharmacokinetics, and pharmacodynamics, and determine a recommended Phase 2 dose [3][11]. - Enrollment for the Phase 1 trial is on track, with expectations to conclude monotherapy dose escalation by mid-2024 [3]. Group 2: Collaboration Details - Under the collaboration agreement, Merck will supply KEYTRUDA for the Phase 2 trial, while Prelude will act as the trial sponsor [4][12]. - Both companies retain all commercial rights to their respective compounds, whether used alone or in combination [4]. Group 3: Mechanistic Rationale - The combination of the SMARCA2 degrader and anti-PD-1 therapy is supported by pre-clinical data, which indicates enhanced anti-tumor immunity and tumor regressions in SMARCA4-mutated cancers [8]. - The rationale for this combination was previously presented at the 2023 AACR International Conference on Molecular Targets and Cancer Therapeutics [8]. Group 4: Company Overview - Prelude Therapeutics is focused on developing innovative drug candidates targeting critical cancer cell pathways, with a pipeline that includes PRT3789, a CDK9 inhibitor (PRT2527), and a next-generation CDK4/6 inhibitor (PRT3645) [11]. - The company is also collaborating with AbCellera to discover and develop next-generation antibody drug conjugate products [11].