IDEAYA Reports Positive Interim Phase 1 Data of IDE397 in MTAP-Deletion Cancers at EORTC-NCI-AACR 2024

IDEAYA Biosciences, Inc., a precision medicine oncology company, has disclosed promising data from its Phase 1 expansion study of IDE397, presented at the EORTC-NCI-AACR Symposium (ENA 2024) in Barcelona. IDE397, an innovative methionine adenosyltransferase 2 alpha (MAT2A) inhibitor, is in Phase 2 clinical trials targeting MTAP-deletion urothelial cancer (UC) and non-small cell lung cancer (NSCLC).

The study evaluated 27 heavily pre-treated MTAP-deletion patients, who had undergone a median of two to three prior treatment lines, up to seven in some cases. The data included 10 UC, nine NSCLC adenocarcinoma, and eight squamous NSCLC patients, all administered a 30 mg daily dose of IDE397.

The clinical efficacy results showed a 33% overall response rate (ORR) according to RECIST 1.1 criteria, with one complete response (CR) and eight partial responses (PRs) confirmed among the 27 patients. All nine responses confirmed by RECIST 1.1 criteria were distributed across different patient groups: four UC patients (including one CR), three squamous NSCLC patients, and two adenocarcinoma NSCLC patients. Additionally, earlier data revealed five confirmed responses out of 18 evaluable patients.

Specifically, for MTAP-deletion UC, the confirmed ORR was 40% (four out of 10 patients), with three patients remaining on treatment for over 250 days. For MTAP-deletion squamous NSCLC, the confirmed ORR was approximately 38% (three out of eight patients), with four patients on treatment for over 200 days. There were also multiple PRs with genetic co-alterations, such as MTAP-deletion with KRAS G12D mutation in NSCLC and MTAP-deletion with FGFR-TACC3 fusion in UC. The median duration of treatment has not been reached but exceeds 6.2 months, with a median time to response of approximately 2.7 months.

The disease control rate (DCR) was notably high at 93%, encompassing one CR, eight PRs, and 16 stable disease (SD) cases out of the 27 evaluable patients. The preliminary durability assessment indicated that 15 of the 27 patients were still under treatment, with seven out of nine RECIST 1.1 responses ongoing. The median duration of response and progression-free survival data remain immature at this stage.

The ctDNA molecular response rate (MRR) was 81%, with 17 out of 21 patients achieving at least a 50% reduction in ctDNA levels, and around 33% showing a deep reduction of 90% or more. All molecular responses were rapid, observed at the first ctDNA sample analysis.

In terms of safety, IDE397 showcased a favorable profile with no drug-related serious adverse events (SAEs) or discontinuations at the 30 mg daily dose. Only 18% of patients experienced grade 3 or higher drug-related adverse events.

IDEAYA plans to expand the Phase 1/2 study of IDE397 in collaboration with Trodelvy® for treating MTAP-deletion UC patients in the fourth quarter of 2024. A case study demonstrating a partial response and a significant reduction in ctDNA levels from this combination will be presented at ENA 2024.

Additionally, preclinical data presented at ENA 2024 highlighted IDE397's potential when used in combination with PRMT5 inhibitors, showcasing deep and lasting tumor regressions. IDEAYA has activated over 35 clinical trial sites globally to facilitate rapid enrollment for the Phase 2 monotherapy expansion in MTAP-deletion lung and bladder cancer.

In summary, IDE397 continues to show significant potential as a monotherapy and in combination treatments for MTAP-deletion cancers, with further clinical developments and trials planned to build on these promising results.