Ideaya Reports Positive Interim Phase 1 Expansion Data Of IDE397 Fro Urothelial and Lung Cancer

Ideaya Reports Positive Interim Phase 1 Expansion Data Of IDE397 Fro Urothelial and Lung Cancer

By, Admin 29 October 2024

Ideaya reports positive interim phase 1 expansion data of IDE397 in MTAP-deletion urothelial and lung cancer as late-breaker oral presentation at ENA 2024

Overview

Ideaya Biosciences, Inc., a precision medicine oncology company committed to the discovery and development of targeted therapeutics, announces phase 1 expansion data for IDE397 in methylthioadenosine phosphorylase (MTAP)-deletion urothelial cancer (UC) and non-small cell lung cancer (NSCLC) patients as a late breaker abstract (LBA) oral presentation at the 36th edition of the EORTC-NCI-AACR Symposium (ENA 2024) in Barcelona, Spain. In addition, Ideaya had additional poster presentations at ENA 2024 highlighting preclinical data for the MAT2A and PARG programmes. IDE397 is a potent and selective potential first-in-class methionine adenosyltransferase 2 alpha (MAT2A) inhibitor in phase 2 clinical trials for the treatment of MTAP-deletion solid tumours.

Statement from an Expert: Columbia University

  • 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.
  • In addition, at the 30mg once-a-day expansion dose, we observed a manageable safety profile with no drug-related serious adverse events or discontinuations. These data support potential combination development,"" said Dr. Benjamin Herzberg, M.D., Assistant Professor of Medicine, Columbia University.

From the CMO: Ideaya Biosciences

The clinical data update from the late breaker oral presentation at ENA 2024 provides further clinical proof-of-concept for IDE397 in the setting of MTAP-deletion urothelial cancer and non-small cell lung cancer to deliver a high disease control rate and confirmed RECIST responses, with an overall manageable adverse event profile,"" said Darrin M. Beaupre, M.D., Ph.D., chief medical officer, Ideaya Biosciences.

From the CEO: Ideaya Biosciences

IDE397 is rapidly advancing as a monotherapy agent in MTAP-deletion urothelial cancer and non-small cell lung cancer. Next, we are well positioned to advance our broad and potential first-in-class IDE397 rational combination strategy, including the targeted expansion in the fourth quarter with Trodelvy in urothelial cancer, the ongoing combination with AMG 193 with targeted expansion in NSCLC, combinations with Ideaya's internal MTAP-deletion pipeline that includes a targeted development candidate by year-end, among others,"" said Yujiro S. Hata, President and chief executive officer, Ideaya Biosciences.

Requirement for Approved for MTAP-Deletion Solid Tumours

  • There are currently no FDA-approved therapies for patients with MTAP-deletion solid tumours, highlighting the unmet medical need. 
  • The priority MTAP-deletion solid tumour types for the IDE397 phase 1/2 monotherapy programme are UC and NSCLC. 
  • MTAP-deletion has been reported at over 15% in NSCLC and over 25% in UC, based on The Cancer Genome Atlas (TCGA) database. 
  • We estimate that the annual incidence of MTAP-deletion in the US in UC and NSCLC 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 tumour 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 in pancreatic cancer has been reported in more than 20% of patients, representing a US annual incidence of approximately 14,000 patients.

Phase 1 Clinical Trial Findings

  • The company observed encouraging clinical activity at the 30 mg once-a-day (QD) Recommended phase 2 Dose (RP2D) in its phase 1 clinical trial evaluating its potential first-in-class MAT2A inhibitor IDE397 in heavily pre-treated MTAP-deletion UC and NSCLC patients. 
  • The patients evaluated had a median of two (2) to three (3) prior lines-of-therapy, ranging from one (1) to seven (7). 
  • The reported phase 1 clinical expansion data are based on twenty-seven (27) evaluable MTAP-deletion patients, including ten (10) UC, nine (9) adenocarcinoma NSCLC, and eight (8) squamous (sq) 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, 2024.

Latest Clinical Data

The clinical data update in the twenty-seven (27) evaluable patients by RECIST 1.1 include:

  • 33% Overall Response Rate (ORR). One (1) complete response (CR) and eight (8) partial responses (PRs) by RECIST 1.1 evaluation out of twenty-seven (27) evaluable patients. 

Nine (9) of nine (9) responses have been confirmed by RECIST 1.1, including four (4) UC patients, of which one was a CR, three (3) squamous NSCLC patients, and two (2) adenocarcinoma NSCLC patients. Two patients confirmed after the data cutoff date. 
In the earlier reported July 8, 2024, IDE397 webcast program update, five (5) confirmed responses were reported out of eighteen (18) evaluable patients. 
There were zero (0) non-evaluable patients reported as of the data analysis

  • Confirmed ORR% by RECIST 1.1 by Solid Tumour Type: MTAP-deletion UC = 40% (4 of 10) confirmed ORR%; MTAP-deletion squamous NSCLC = ~38% (3 of 8) confirmed ORR%; MTAP-deletion adenocarcinoma NSCLC = ~22% (2 of 9) confirmed ORR%
  • Multiple confirmed partial responses by RECIST 1.1 harbour 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 (DCR). One (1) CR, eight (8) PRs, and sixteen (16) stable disease (SD) by RECIST 1.1 evaluation out of twenty-seven (27) evaluable patients.
  • Preliminary durability assessment: Fifteen (15) of twenty-seven (27) patients still on treatment. Seven (7) of nine (9) RECIST 1.1 responses remain on treatment. 

Median duration of treatment (DOT) has not been reached and is greater than 6.2 months and median time to response (TTR) is ~2.7 months. 
The median duration of response and median progression free survival data is still immature. 
Three (3) UC patients on treatment greater than 250 days, four (4) squamous NSCLC patients on treatment greater than 200 days, and three (3) adenocarcinoma NSCLC patients on treatment greater than 200 days

  • 81% ctDNA Molecular Response Rate (MRR). Seventeen (17) of twenty (21) patients with 50% or greater ctDNA reduction, and ~33% (7 of 21) with deep 90% or greater ctDNA reduction. 

All MRs (17 of 17) 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.

  • Favourable adverse event (AE) profile. Approximately 18% grade 3 or higher drug-related AEs and no drug-related serious adverse events (SAEs) observed at the IDE397 30mg once-a-day expansion dose. 

No Drug-Related AEs Leading to Discontinuations Were Observed. 

We anticipate that the favourable 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 (ADCs)

IDE397 and Trodelvy Combination: 1st Case Study

  • 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.

Overall active Trial sites: Ideaya

  • Ideaya has activated over 35 clinical trial sites globally in the US, 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 (NCT04794699). 
  • There is also an ongoing Amgen-sponsored phase 1/2 trial of the IDE397 and AMG 193 combination in MTAP-Deletion NSCLC (NCT05975073). 
  • 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.

Enrollment for Phase 1 Clinical Trial

  • 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 (NCT04794699). 
  • 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.

About Ideaya

Ideaya is a precision medicine oncology company committed to the discovery and development of targeted therapeutics for patient populations selected using molecular diagnostics.

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