Ideaya Biosciences announces IDE397 expansion data

Ideaya Biosciences (IDYA) announced Phase 1 expansion data for IDE397 in methylthioadenosine phosphorylase, or MTAP-deletion urothelial cancer, or UC, and non-small cell lung cancer, or NSCLC, patients as a late breaker abstract, or LBA, oral presentation at the 36th edition of the EORTC-NCI-AACR Symposium, or ENA 2024, in Barcelona, Spain. In addition, IDEAYA had additional poster presentations at ENA 2024 highlighting preclinical data for the MAT2A and PARG programs. IDE397 is a potent and selective potential first-in-class methionine adenosyltransferase 2 alpha, or MAT2A, inhibitor in Phase 2 clinical trials for the treatment of MTAP-deletion solid tumors. The company observed encouraging clinical activity at the 30 mg once-a-day Recommended Phase 2 Dose in its Phase 1 clinical trial evaluating its MAT2A inhibitor IDE397 in heavily pre-treated MTAP-deletion UC and NSCLC patients. The patients evaluated had a median of two to three prior lines-of-therapy, ranging from one to seven. The reported Phase 1 clinical expansion data are based on 27 evaluable MTAP-deletion patients, including ten UC, nine adenocarcinoma NSCLC, and eight squamous NSCLC patients at the expansion dose of 30 mg QD of IDE397. The clinical efficacy and tolerability data are preliminary and based on investigator review from an unlocked database as of the data analysis cutoff date of August 22. The clinical data update in the twenty-seven evaluable patients by RECIST 1.1 include: 33% overall response rate, or ORR. One complete response and eight partial responses by RECIST 1.1 evaluation out of 27 evaluable patients. Nine of nine responses have been confirmed by RECIST 1.1, including four UC patients, of which one was a CR, three squamous NSCLC patients, and two adenocarcinoma NSCLC patients. Two patients confirmed after the data cutoff date. In the earlier reported July 82, IDE397 webcast program update, five confirmed responses were reported out of eighteen evaluable patients. There were zero non-evaluable patients reported as of the data analysis. Confirmed ORR% by RECIST 1.1 by Solid Tumor Type: MTAP-deletion UC =40% confirmed ORR%; MTAP-deletion squamous NSCLC ~38% confirmed ORR%; MTAP-deletion adenocarcinoma NSCLC = 22% confirmed ORR%. Multiple confirmed partial responses by RECIST 1.1 harbor genetic co-alterations, including MTAP-deletion and KRAS G12D mutation in NSCLC, and MTAP-deletion and FGFR-TACC3 fusion in UC, 93% Disease Control Rate. One CR, eight PRs, and sixteen stable disease by RECIST 1.1 evaluation out of twenty-seven evaluable patients. Preliminary durability assessment: Fifteen of twenty-seven patients still on treatment. Seven of nine RECIST 1.1 responses remain on treatment. Median duration of treatment has not been reached and is greater than 6.2 months and median time to response is 2.7 months. The median duration of response and median progression free survival data is still immature. Three UC patients on treatment greater than 250 days, four squamous NSCLC patients on treatment greater than 200 days, and three adenocarcinoma NSCLC patients on treatment greater than 200 days 81% ctDNA Molecular Response Rate. Seventeen of twenty patients with 50% or greater ctDNA reduction, and 33% with deep 90% or greater ctDNA reduction. All MRs were rapid occurring at the first ctDNA sample analysis. There were several quality control failures of patient samples that led to unavailability for MR analysis. Favorable adverse event profile. Approximately 18% grade 3 or higher drug-related AEs and no drug-related serious adverse events observed at the IDE397 30mg once-a-day expansion dose. No drug-related AEs leading to discontinuations were observed. The company anticipates that the favorable AE profile and dosing convenience of a 30 mg once-a-day tablet has the potential to enable long-term dosing and combination development, including with MTA-cooperative PRMT5 inhibitors and topoisomerase payload antibody drug conjugates. Ideaya reports the first preliminary clinical case study of the IDE397 and Trodelvy combination in MTAP-deletion UC, including a PR by RECIST 1.1 in a patient case report with a genetic co-alteration of MTAP-deletion and a FGFR3-TACC3 fusion, and rapid and deep first-evaluation molecular responses with ctDNA reduction of greater than 95% observed that will be presented at ENA 2024. IDEAYA is targeting to initiate the IDE397 and Trodelvy Phase 1/2 combination expansion in MTAP-deletion UC in Q4 2024. Ideaya has activated over 35 clinical trial sites globally in the U.S., Canada, Europe, and Asia Pacific to enable potential rapid enrollment for the IDE397 Phase 2 monotherapy expansion in MTAP-deletion lung and bladder cancer in its ongoing trial. There is also an ongoing Amgen-sponsored Phase 1/2 trial of the IDE397 and AMG 193 combination in MTAP-Deletion NSCLC. Ideaya published at ENA 2024 preclinical combination efficacy data and the combination mechanistic rationale for IDE397 with clinical stage PRMT5 inhibitors, including BMS-986504 and AMG 193. Next, Ideaya is enrolling a Phase 1 clinical trial evaluating the safety, tolerability, pharmacokinetics, pharmacodynamics and efficacy of IDE397 in combination with Trodelvy in MTAP-deletion UC patients. Pursuant to the clinical study collaboration and supply agreement, Ideaya and Gilead retain the commercial rights to their respective compounds, including with respect to use as a monotherapy or combination agent. Ideaya is the study sponsor and Gilead will provide the supply of Trodelvy to IDEAYA. IDE397 monotherapy or in combination with Trodelvy has not been approved by any regulatory agency and the efficacy and safety of this combination has not been established.