Positive Interim Phase II Data Show Strong Overall Response and Disease Control Rates for MAT2A Inhibitor, IDE397

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IDEAYA Biosciences has shared positive clinical data for the IDE397 Phase II monotherapy expansion dose in methylthioadenosine phosphorylase (MTAP)-deletion urothelial and non-small cell lung cancer (NSCLC) patients. IDE397 is a potential first-in-class methionine adenosyltransferase 2 alpha (MAT2A) inhibitor for the treatment of MTAP-deletion solid tumors.¹

Preliminary results showed a 39% overall response rate and a disease control rate of 94% at the 30 mg expansion dose. Out of 18 patients, the RECIST 1.1 evaluation showed one complete response and six partial responses. Additionally, data indicated that 14 patients observed tumor shrinkage and 13 of 16 patients had > 50% ctDNA reduction.

"We are highly encouraged by the preliminary clinical efficacy and favorable safety profile observed with IDE397 at the 30mg once-a-day expansion dose, including multiple partial responses and one complete response by RECIST 1.1 in MTAP-deletion urothelial and lung cancer patients. In addition, at this expansion dose we observed a favorable adverse event profile with no drug-related serious adverse events and mid-single digit percent grade 3 or higher drug-related adverse events, which we believe has the potential to enable longer duration dosing as well as combinations," Darrin Beaupre, MD, PhD, chief medical officer of IDEAYA Biosciences said in a press release.

Yujiro S. Hata, chief executive officer and founder of IDEAYA Biosciences added: "IDE397 is a potential first-in-class MAT2A inhibitor, that is being advanced as a monotherapy agent in priority MTAP-deletion solid tumor types and in high conviction rational combinations, including with Amgen's investigational MTA-cooperative protein arginine methytranferase 5 inhibitor AMG 193 in NSCLC and with Gilead's Trop-2 directed anti-body conjugate Trodelvy in urothelial cancer. The IDE397 clinical data update demonstrates important clinical proof-of-concept in MTAP-deletion solid tumors to deliver RECIST responses and encouraging preliminary durability, with a convenient 30mg once-a-day tablet and favorable adverse event profile.”

In June, IDEAYA announced it had dosed the first patient in its Phase I trial (NCT04794699) evaluating the combination of IDE397 and Gilead’s Trop-2 directed ADC, Trodelvy (sacituzumab govitecan-hziy) in patients with MTAP-deletion bladder cancer.² The Phase I trial is an open-label, multicenter, dose escalation, and expansion study.³

This collaboration between IDEAYA and Gilead was officially announced in December 2023. Under the agreement, IDEAYA is sponsoring the previously mentioned Phase I clinical trial and Gilead is providing the Trodelvy supply. The organizations will each retain all commercial rights to their respective compounds, including as a monotherapy or as combination therapies.⁴

"We are delighted to enter into this clinical collaboration with Gilead that advances our multi-pronged strategy designed to deliver maximal benefit to MTAP-deletion solid tumor patients. We believe the strong mechanistic rationale of this combination, and the monotherapy efficacy observed by both agents in MTAP-deletion bladder cancer, may enable this combination to be differentiated and studied in an earlier-line clinical setting," Hata said in an earlier press release.

References

1. IDEAYA Announces Positive Interim Phase 2 Monotherapy Expansion Data for IDE397 a Potential First-in-Class MAT2A Inhibitor in MTAP-Deletion Urothelial and Lung Cancer. News release. IDEAYA Biosciences. July 8, 2024. Accessed July 9, 2024. https://ir.ideayabio.com/2024-07-08-IDEAYA-Announces-Positive-Interim-Phase-2-Monotherapy-Expansion-Data-for-IDE397-a-Potential-First-in-Class-MAT2A-Inhibitor-in-MTAP-Deletion-Urothelial-and-Lung-Cancer

2. IDEAYA Biosciences Announces First-Patient-In for Phase 1 Clinical Trial Evaluating IDE397 and Trodelvy® Combination in MTAP-Deletion Bladder Cancer. News release. IDEAYA Biosciences. June 25, 2024. Accessed July 9, 2024. https://ir.ideayabio.com/2024-06-25-IDEAYA-Biosciences-Announces-First-Patient-In-for-Phase-1-Clinical-Trial-Evaluating-IDE397-and-Trodelvy-R-Combination-in-MTAP-Deletion-Bladder-Cancer

3. Study of IDE397 in Participants With Solid Tumors Harboring MTAP Deletion. ClinicalTrials.gov. Accessed July 9, 2024. https://clinicaltrials.gov/study/NCT04794699

4. IDEAYA Announces Clinical Study Collaboration with Gilead Sciences to Evaluate Trodelvy® and IDE397 Combination in MTAP-Deletion Bladder Cancer. News release. IDEAYA Biosciences. December 4, 2023. Accessed July 9, 2024. https://media.ideayabio.com/2023-12-04-IDEAYA-Announces-Clinical-Study-Collaboration-with-Gilead-Sciences-to-Evaluate-Trodelvy-R-and-IDE397-Combination-in-MTAP-Deletion-Bladder-Cancer