IDE397 shows promise in MTAP-deletion urothelial carcinoma

IDEAYA Biosciences has reported interim efficacy and safety data from a phase 2 monotherapy dose expansion study (NCT04794699) of IDE397, an investigational MAT2A inhibitor, in patients with methylthioadenosine phosphorylase (MTAP)-deletion urothelial carcinoma and non-small-cell lung cancer (NSCLC).¹

A phase 1 study of IDE397 in combination with sacituzumab govitecan in MTAP-deletion bladder cancer was initiated in June 2024.

"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 1 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," said Darrin Beaupre, MD, PhD, chief medical officer of IDEAYA Biosciences, in a news release from the company.¹

In total, reported findings encompassed data from 18 evaluable patients who received a 30-mg once-daily expansion dose of IDE397. Of those included for analysis, 7 patients had urothelial carcinoma. The median prior lines of therapy among all patients included in the trial was 2, with a range from 1 to 7.

Overall, data showed an overall response rate of 39% among all evaluable patients, including 1 complete response and 6 partial responses per RECIST 1.1. Of those, 1 complete response and 2 partial responses were from patients with urothelial carcinoma. At the time of data collection, 2 partial responses were pending confirmation, including 1 in a patient with urothelial carcinoma who experienced a 100% tumor reduction in the target lesion at the last CT scan assessment.

The disease control rate in the study was 94%, which included 1 complete response, 6 partial responses, and 10 patients with stable disease per RECIST 1.1. Further, 78% of patients achieved tumor shrinkage. The ctDNA molecular response rate, defined as a 50% or greater reduction in ctDNA, was 81%.

Regarding safety, grade 3 or higher drug-related adverse events (AEs) were reported in 5.6% of patients. No drug-related serious AEs or drug-related AEs leading to treatment discontinuation were observed.

At the time of data report, 11 of 18 patients remained on treatment, and 5 of 7 patients who achieved a response remain in response. The median duration of treatment, duration of response, and progression-free survival have not yet been reached.

This data report follows the initiation of a phase 1 study of IDE397 in combination with sacituzumab govitecan-hziy (Trodelvy) in MTAP-deletion bladder cancer in June 2024.² Overall, the phase 1 trial is assessing the safety, tolerability, pharamacokinetics, pharmacodynamics, and preliminary efficacy of IDE397 in combination with sacituzumab govitecan in adult patients with bladder cancer. The study is being conducted as an arm in the larger, ongoing clinical trial of IDE397 in combination with other agents in adult patients with advanced or metastatic MTAP-deleted solid tumors.

Yujiro S. Hata, chief executive officer and founder of IDEAYA Biosciences, concluded in the news release,¹ "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.”

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, Inc. Published online and accessed July 8, 2024. https://www.prnewswire.com/news-releases/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-302190321.html

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, Inc. June 25, 2024. Accessed July 8, 2024. https://www.prnewswire.com/news-releases/ideaya-biosciences-announces-first-patient-in-for-phase-1-clinical-trial-evaluating-ide397-and-trodelvy-combination-in-mtap-deletion-bladder-cancer-302181366.html