IDE397 Plus Sacituzumab Shows Promise in MTAP-Deletion Bladder Cancer

Data from 2 expansion cohorts of the phase 1/2 study (NCT04794699) of IDE397 combined with the TROP2-directed antibody-drug conjugate sacituzumab govitecan (Trodelvy) in patients with late-line methylthioadenosine phosphorylase (MTAP)-deletion urothelial cancer (UC) show promising responses and safety, offering a potential new targeting for this disease state.¹

At dose level 2, the overall response rate (ORR) was 57% (n = 4 of 7), consisting of 3 confirmed partial responses (PRs) and 1 unconfirmed PR in patients treated with a combination of 30 mg of IDE397 plus 7.5 mg/kg of sacituzumab govitecan. At dose level 1, the ORR was 33% (n = 3 of 9), consisting of 3 confirmed PRs with 15 mg IDE397 and 10 mg/kg sacituzumab govitecan.

"We are pleased with the progress we are making with the [sacituzumab govitecan] and IDE397 combination and are encouraged by the early response rate data we are seeing in previously treated MTAP-deleted urothelial cancer,” said Darrin Beaupre, chief medical officer, IDEAYA Biosciences, in a press release.

The safety profile at both dose levels appeared manageable and was consistent with the known profiles of the agents individually. There were no treatment-related serious adverse events (AEs) observed at dose level 2. The most common grade 3 or greater treatment-related AEs seen in dose level 1 were anemia and neutropenia, and, in dose level 2, were anemia, asthenia, and diarrhea.

Further, the median progression-free survival and duration of response have not been reached.

Based on these data, the selection of the recommended phase 2 dose is anticipated for the end of 2025, and the next update is anticipated at a medical meeting in the first half of 2026.

These results set the stage for further testing of the combination in non–small cell lung cancer [NSCLC], where we have just dosed the first patient in our clinical trial," Beaupre added in the press release.

About the Phase 1/2 Clinical Trial

The phase 1/2 study is recruiting patients with select advanced or metastatic MTAP-deleted advanced solid tumors across 38 sites in the US, Australia, France, Germany, South Korea, Spain, and Taiwan.²

The primary end points are dose-limiting toxicities, maximum tolerated dose, and preliminary antitumor activity. Secondary end points include pharmacokinetics, drug interactions, and pharmacodynamics.

The study is composed of 6 parts:

• Part 1: Dose escalation monotherapy in solid tumors
• Part 2: Monotherapy dose expansion in NSCLC, esophageal cancer, and urothelial carcinoma
• Part 3: Combination dose escalation with docetaxel or paclitaxel in NSCLC, esophageal cancer, and urothelial carcinoma
• Part 4: Combination dose expansion with docetaxel or paclitaxel in NSCLC, esophageal cancer, and urothelial carcinoma
• Part 5: Combination dose escalation with sacituzumab govitecan in urothelial carcinoma
• Part 6: Combination dose expansion with sacituzumab govitecan in urothelial carcinoma.

Patients are eligible for enrollment if they have advanced or metastatic disease that has progressed on at least 1 prior line of treatment or is intolerant to additional effective standard therapy, have evidence of homozygous loss of MTAP or MTAP deletion, an ECOG performance status of 0 to 1, adequate organ function, and are recovered from acute effects of prior therapy. Those with known symptomatic brain metastases, a known primary central nervous system malignancy, current active liver or biliary disease, impaired gastrointestinal function, active uncontrolled infection, or clinically significant cardiac abnormalities are not eligible for participation in the study.

REFERENCES

1. 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. News release. IDEAYA Biosciences. September 8, 2025. Accessed September 10, 2025. https://tinyurl.com/ycth8xpf

2. Study of IDE397 in participants with solid tumors harboring MTAP deletion. ClinicalTrials.gov. Updated November 18, 2024. Accessed September 10, 2025. https://clinicaltrials.gov/study/NCT04794699