Ideaya Biosciences announced positive interim Phase 1 expansion data for IDE397, a methionine adenosyltransferase 2 alpha (MAT2A) inhibitor, in patients with methylthioadenosine phosphorylase (MTAP)-deletion urothelial cancer (UC) and non-small cell lung cancer (NSCLC). The data, presented at the 36th EORTC-NCI-AACR Symposium (ENA 2024), highlight the potential of IDE397 as a monotherapy and in combination strategies for these cancers.
Clinical Efficacy and Safety
The Phase 1 clinical expansion data are based on twenty-seven evaluable MTAP-deletion patients, including ten UC, nine adenocarcinoma NSCLC, and eight squamous NSCLC patients, all treated with 30 mg QD of IDE397. These patients had received a median of two to three prior lines of therapy.
The clinical data update showed:
- ~33% Overall Response Rate (ORR): One complete response (CR) and eight partial responses (PRs) were observed.
- Confirmed ORR by RECIST 1.1 by Solid Tumour Type: MTAP-deletion UC = 40% (4 of 10); MTAP-deletion squamous NSCLC = ~38% (3 of 8); MTAP-deletion adenocarcinoma NSCLC = ~22% (2 of 9).
- ~93% Disease Control Rate (DCR): One CR, eight PRs, and sixteen stable disease (SD) were observed.
- ~81% ctDNA Molecular Response Rate (MRR): Seventeen of twenty-one patients showed a 50% or greater ctDNA reduction.
The safety profile was favorable, with approximately 18% grade 3 or higher drug-related adverse events and no drug-related serious adverse events observed at the 30mg once-a-day expansion dose. No drug-related adverse events led to discontinuations.
Combination Strategies and Future Directions
Ideaya is also exploring combination strategies with IDE397. Preliminary clinical case study data of the IDE397 and Trodelvy combination in MTAP-deletion UC showed a PR by RECIST 1.1 in a patient with a genetic co-alteration of MTAP-deletion and a FGFR3-TACC3 fusion. The company is targeting to initiate the IDE397 and Trodelvy Phase 1/2 combination expansion in MTAP-deletion UC in Q4 2024.
"We are excited by the clinical efficacy and safety profile observed with the potential first-in-class MAT2A inhibitor IDE397 at the 30mg once-a-day RP2D, including multiple confirmed responses observed as a monotherapy agent in non-small cell lung cancer and urothelial cancer patients with MTAP-deletion," said Dr. Benjamin Herzberg, M.D., Assistant Professor of Medicine, Columbia University.
Unmet Need in MTAP-Deletion Cancers
There are currently no FDA-approved therapies for patients with MTAP-deletion solid tumors, highlighting the unmet medical need. MTAP-deletion has been reported at over 15% in NSCLC and over 25% in UC. Ideaya estimates that the annual incidence of MTAP-deletion in the US in UC and NSCLC is approximately 48,000 patients.
Ideaya has activated over 35 clinical trial sites globally to enable potential rapid enrollment for the IDE397 Phase 2 monotherapy expansion in MTAP-deletion lung and bladder cancer. There is also an ongoing Amgen-sponsored Phase 1/2 trial of the IDE397 and AMG 193 combination in MTAP-Deletion NSCLC.
