IDEAYA Biosciences has announced positive interim results for its MAT2A inhibitor Phase II trial in urothelial and non-small cell lung cancer (NSCLC). IDE397 is a potential first-in-class methionine adenosyltransferase 2 alpha (MAT2A) inhibitor targeting MTAP-deletion solid tumors. The trial looked at an expansion dose, which seems to show efficacy and be safe. There are currently no FDA-approved therapies for patients with MTAP-deletion solid tumors.
“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,” said said Yujiro S. Hata, CEO and Founder, IDEAYA Biosciences.
Highlights included:
- ~39% Overall Response Rate (ORR): 1 CR and 6 PRs (2 awaiting confirmation) by RECIST 1.1 out of 18 evaluable MTAP-deletion urothelial and NSCLC patients.
- ~94% Disease Control Rate (DCR): 1 CR and 6 PRs and 10 SD by RECIST 1.1.
- ~78% of Patients with Tumor Shrinkage: 14 patients observed tumor shrinkage.
- ~81% ctDNA Molecular Response Rate (MRR): 13 of 16 patients with > 50% ctDNA reduction.
The drug is being advanced as a monotherapy agent in MTAP-deletion solid tumor types and also in several combinations, including with Amgen’s investigational MTA-cooperative protein arginine methytranferase 5 inhibitor AMG 193 in NSCLC, and with Gilead’s Trop-2 directed antibody conjugate Trodelvy in urothelial cancer.
“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,” said Darrin Beaupre, MD, PhD, chief medical officer, IDEAYA.
MTAP-deletion prevalence has been reported at over 15% in NSCLC and over 25% in urothelial cancer, based on The Cancer Genome Atlas (TCGA) database. The company estimates that the MTAP-deletion annual incidence in the U.S. in NSCLC and urothelial cancer is approximately 48,000 patients, based on the 2024 Surveillance, Epidemiology, and End Results (SEER) database. In addition, there are several potential expansion MTAP-deletion solid tumor types that are also being considered for monotherapy and combination development, including pancreatic, gastric, esophageal, and head and neck cancer, among others. Based on the TCGA database, MTAP-deletion prevalence in pancreatic cancer has been reported at over 20%, representing a U.S. annual incidence of approximately 14,000 patients.
The company observed encouraging clinical activity at the 30 mg expansion dose in its Phase II clinical trial evaluating IDE397 in heavily pre-treated MTAP-deletion urothelial cancer and NSCLC patients. The patients evaluated had a median of two prior lines of therapy, ranging from one to seven. The reported Phase II clinical data are based on eighteen evaluable MTAP-deletion patients, including seven with urothelial cancer, four with adenocarcinoma NSCLC, and seven with squamous NSCLC. All patients were treated at the expansion dose of 30 mg once-a-day of IDE397.
