Prelude Therapeutics Incorporated, a clinical-stage precision oncology company, has entered into a clinical trial collaboration and supply agreement with Merck & Co., under which a Phase 2 clinical study will evaluate PRT3789, Prelude’s investigational, highly selective, first-in-class SMARCA2 degrader in combination with KEYTRUDA (pembrolizumab) Merck’s anti-PD-1 therapy, in patients with SMARCA4-mutated cancers.

“We are excited for this opportunity to work together with Merck on this study combining our novel, highly selective SMARCA2 degrader with KEYTRUDA,” stated Prelude’s President and Chief Medical Officer Jane Huang, M.D. “Through this collaboration of potentially complementary mechanisms, we may have the potential to positively impact clinical outcomes in patients harboring a SMARCA4 mutation, who have previously been known to have limited treatment options.”

PRT3789 is a potent and highly selective, first-in-class SMARCA2 degrader, in Phase 1 clinical development in biomarker selected SMARCA4 mutant patients. Enrollment remains on track, and Prelude expects to conclude monotherapy dose escalation mid-2024 and identify recommended Phase 2 dose. In addition, enrollment of patients into back-fill cohorts enriched for NSCLC and SMARCA4 loss-of-function mutations is ongoing.

Objectives for this first Phase 1 clinical study are to establish the safety and tolerability profile of PRT3789 as both monotherapy and in combination with docetaxel, evaluate activity, pharmacokinetics and pharmacodynamics and determine a dose and potential indications for advancement into a registrational clinical trial.

The mechanistic rationale and pre-clinical data to support the SMARCA2 and anti-PD-1 monoclonal antibody (mAb) combination was previously presented by Prelude at the 2023 AACR International Conference on Molecular Targets and Cancer Therapeutics. In pre-clinical models, SMARCA2 degrader combined with an anti-PD-1 mAb in SMARCA4-mutated cancers enhanced anti-tumor immunity and demonstrated tumor regressions.

Under the terms of the Agreement, Merck will provide KEYTRUDA to Prelude, which will be the sponsor of the Phase 2 clinical combination trial. Prelude and Merck each retain all commercial rights to their respective compounds, including as monotherapy or as combination therapies.