IDEAYA Biosciences Announces Positive Data From Phase 1/2 Combination Trial of IDE397, a potential first-in-class MAT2A inhibitor, and Trodelvy® in MTAP-Deletion Urothelial Cancer

• Overall response rate (ORR) of 57% (4/7; 3cPR+1uPR) in patients treated with a combination of 30 mg IDE397 plus 7.5mg/kg Trodelvy® (Dose level 2); ORR of 33% (3/9; 3cPR) at 15 mg IDE397 plus 10mg/kg Trodelvy® (Dose level 1)
• Manageable safety profile at both expansion doses, consistent with known adverse events observed with each agent alone, with no treatment related serious adverse events observed at the IDE397 30mg and Trodelvy® 7.5 mg/kg expansion dose
• Selection of recommended Phase 2 dose is targeted by end of 2025, with next update planned for a medical conference in H1 2026  

SOUTH SAN FRANCISCO, Calif., Sept. 8, 2025 /PRNewswire/ -- IDEAYA Biosciences, Inc. (Nasdaq: IDYA), a leading precision medicine oncology company, will present initial data at their 10-Year Anniversary R&D Day from two expansion cohorts in their Phase 1/2 combination trial of IDE397, a potential first-in-class, small molecule adenosyltransferase 2a (MAT2A) inhibitor, in combination with Gilead's Trodelvy® (sacituzumab govitecan-hziy), a Trop2-directed antibody-drug conjugate (ADC), in patients with late-line methylthioadenosine phosphorylase (MTAP)-deletion urothelial cancer (UC).  MTAP-deletion is estimated to occur in approximately 25-30% of UC and 15-20% of non-small cell lung cancer (NSCLC) patients.  There are currently no therapies approved by the U.S. Food and Drug Administration (FDA) for patients with MTAP-deletion solid tumors.

Data in the presentation were as of a cut-off date of August 29, 2025, and included a total of 19 patients with late-line MTAP-deletion UC who received the combination of IDE397 and Trodelvy.  Of the 19 patients, 16 (Cohort 1: n=9; Cohort 2: n=7) were evaluable for efficacy having received at least one post-baseline tumor assessment per RECIST v1.1.  Of the patients evaluated in the combination trial, 68% (13/19) had progressed after two or more prior therapies, with 84% (16/19) having received an immune-oncology therapy and 32% (6/19) having received enfortumab vedotin (EV).

"We are pleased with the progress we are making with the Trodelvy and IDE397 combination and are encouraged by the early response rate data we are seeing in previously treated MTAP-deleted urothelial cancer.  These results set the stage for further testing of the combination in non-small cell lung cancer, where we have just dosed the first patient in our clinical trial," said Darrin Beaupre, Chief Medical Officer, IDEAYA Biosciences. 

Summary of key findings

• To date, median progression free survival (PFS) and duration of response (DOR) has not been reached.
• 33% ORR at DL1 (3/9); 3 confirmed partial responses (cPR), including one patient with a confirmed response after the cut-off date, and 57% ORR at DL2 (3 cPR and 1 unconfirmed partial response (uPR)). The preliminary combination data is trending favorably versus historical Trodelvy monotherapy efficacy reported in metastatic UC, including 11% ORR in patients post-EV therapy (Sternschuss et al., 2025) and 23% ORR in predominantly EV-naïve patients (Powles et al., 2025).
• Manageable safety profile consistent with known adverse events of both drugs as single agents, with no treatment related serious adverse events observed at the IDE397 30mg and Trodelvy® 7.5 mg/kg expansion dose. The most common Grade 3 or greater treatment-related adverse events seen in DL1 were anemia and neutropenia, and in DL2 were anemia, asthenia, and diarrhea.

Pursuant to the clinical study collaboration and supply agreement, IDEAYA and Gilead retain the commercial rights to their respective compounds, including with respect to use as a monotherapy or combination agent. IDEAYA is the study sponsor and Gilead will provide the supply of Trodelvy to IDEAYA.

Trodelvy is currently approved in more than 50 countries for second-line or later metastatic triple-negative breast cancer (TNBC) patients and in more than 40 countries for certain patients with pre-treated HR+/HER2- metastatic breast cancer.

The use of Trodelvy in MTAP-deletion UC and NSCLC is investigational, and the safety and efficacy of this use have not been established. IDE397 monotherapy or in combination with Trodelvy has not been approved by any regulatory agency and the efficacy and safety of this combination has not been established.

Trodelvy and Gilead are trademarks of Gilead Sciences, Inc., or its related companies.

IDEAYA will review this data at their 10-Year Anniversary R&D Day on September 8^th in New York.  A link to the webcast is available on the Investor Relations page of the IDEAYA corporate website: https://ir.ideayabio.com/. 

About IDEAYA Biosciences

IDEAYA is a precision medicine oncology company committed to the discovery, development, and commercialization of transformative therapies for cancer.  Our approach integrates expertise in small-molecule drug discovery, structural biology and bioinformatics with robust internal capabilities in identifying and validating translational biomarkers to develop tailored, potentially first-in-class targeted therapies aligned to the genetic drivers of disease.  We have built a deep pipeline of product candidates focused on synthetic lethality and antibody-drug conjugates, or ADCs, for molecularly defined solid tumor indications.  Our mission is to bring forth the next wave of precision oncology therapies that are more selective, more effective, and deeply personalized with the goal of altering the course of disease and improving clinical outcomes for patients with cancer.

Forward-Looking Statements

This press release contains forward-looking statements, including, but not limited to, statements related to (i) the potential therapeutic benefits of IDE397 and Trodelvy combination; (ii) the timing and content of data at the IDEAYA 10 -Year Anniversary R&D Day and an update at a later medical conference; and (iii) the timing of the selection of go-forward combination dose of IDE397/ Trodelvy®.  Such forward-looking statements involve substantial risks and uncertainties that could cause IDEAYA's preclinical and clinical development programs, future results, performance or achievements to differ significantly from those expressed or implied by the forward-looking statements. Such risks and uncertainties include, among others, the uncertainties inherent in the drug development process, including IDEAYA's programs' early stage of development, the process of designing and conducting preclinical and clinical trials, the regulatory approval processes, the timing of regulatory filings, the challenges associated with manufacturing drug products, IDEAYA's ability to successfully establish, protect and defend its intellectual property, and other matters that could affect the sufficiency of existing cash to fund operations. IDEAYA undertakes no obligation to update or revise any forward-looking statements. For a further description of the risks and uncertainties that could cause actual results to differ from those expressed in these forward-looking statements, as well as risks relating to the business of IDEAYA in general, see IDEAYA's Annual Report on Form 10-K dated February 18, 2025 and any current and periodic reports filed with the U.S. Securities and Exchange Commission.

Investor and Media Contact

IDEAYA Biosciences
Joshua Bleharski, Ph.D.
Chief Financial Officer  
[email protected]

SOURCE IDEAYA Biosciences, Inc.