IDEAYA Biosciences, Inc. (Nasdaq: IDYA) has commenced a Phase 1 clinical trial evaluating IDE161, a potential first-in-class poly (ADP-ribose) glycohydrolase (PARG) inhibitor, in combination with Merck’s anti-PD-1 therapy, Keytruda (pembrolizumab), in patients with endometrial cancer. The first patient has been dosed in the IDEAYA-sponsored trial, marking a significant step in the development of this novel combination therapy.
The Phase 1 trial (IDE161-001, NCT05787587) aims to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and efficacy of IDE161 in combination with Keytruda in patients with both high microsatellite instability (MSI-high) and microsatellite stable (MSS) endometrial cancer. This study is designed to explore the potential of PARG inhibition in enhancing the effectiveness of immune checkpoint blockade in this patient population.
Rationale for the Combination
Dr. Darrin M. Beaupre, M.D., Ph.D., Chief Medical Officer of IDEAYA Biosciences, stated, “We continue to progress our IDE161 program and are excited to have the first patient dosed evaluating IDE161 in combination with KEYTRUDA in MSI-high and MSS endometrial cancer patients. This trial is part of our overall IDE161 clinical combination strategy that is focused on high conviction rational combinations.”
Dr. Panos Konstantinopoulos, M.D., Ph.D., Director of Translational Research in the Division of Gynecologic Oncology at Dana-Farber Cancer Institute, added, “We are continually looking for ways to improve outcomes for patients with MSI-high and MSS endometrial cancer, and PARG has shown promising potential as a precision oncology target in these settings. IDE161 has shown robust anti-tumor activity in preclinical models, and I look forward to evaluating IDE161’s impact on endometrial cancer patients in combination with KEYTRUDA.”
IDE161: A Potential First-in-Class PARG Inhibitor
IDE161 is a potential first-in-class inhibitor of poly(ADP-ribose) glycohydrolase (PARG), a mechanistically distinct target in the same clinically validated biological pathway as poly(ADP-ribose) polymerase (PARP). IDE161 has received FDA Fast Track designation for platinum-resistant advanced or metastatic ovarian cancer with BRCA1/2 mutations, and for pretreated advanced or metastatic HR+, Her2-, BRACA1/2 mutant breast cancer.
Trial Collaboration and Design
Under the clinical trial collaboration and supply agreement, Merck will provide Keytruda to IDEAYA, who is sponsoring the Phase 1 clinical combination trial. Both IDEAYA and Merck retain all commercial rights to their respective compounds, both as monotherapies and in combination therapies. The trial, IDE161-001 (NCT05787587), is also evaluating IDE161 monotherapy, and an initial Phase 1/2 monotherapy expansion dose has been selected in a priority tumor type based on the adverse event profile and preliminary clinical efficacy observed.
