On September 8, 2025 IDEAYA Biosciences, Inc. (Nasdaq: IDYA), a leading precision medicine oncology company, reported it 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) (Press release, Ideaya Biosciences, SEP 8, 2025, View Source [SID1234655840]). 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.

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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

Dose Level 1 (DL1)

Dose Level 2 (DL2)

IDE397 (15mg) + Trodelvy (10mg/kg)

IDE397 (30mg) + Trodelvy (7.5mg/kg)

Evaluable patients (n)

n=9

n=7

ORR (cPR+uPR)

33% (3cPR)

57% (3cPR +1uPR)

DCR%

100% (9/9)

71% (5/7)

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.