The US Food and Drug Administration (FDA) has approved an investigational new drug application from IDEAYA to begin a Phase I/II clinical trial of IDE397 alongside AMG 193 for solid tumours.
The study will assess the tolerability, efficacy, safety, pharmacokinetics and pharmacodynamics of IDE397 and AMG 193 in solid tumours with methylthioadenosine phosphorylase (MTAP) deletion.
IDEAYA Biosciences chief medical officer Dr Darrin Beaupre said: “We believe that evaluation of this combination represents an exciting and highly rational clinical study for patients with MTAP-deletion tumours, based on the observed preclinical efficacy, tolerability and selectivity.
“We believe that evaluation of this combination represents an exciting and highly rational clinical study for patients with MTAP-deletion tumors, based on the observed preclinical efficacy, tolerability and selectivity.”
IDE397 is a potent and selective small molecule inhibitor that targets methionine adenosyltransferase 2a (MAT2A).
The drug is being evaluated as a single agent.
Amgen’s AMG 193 is an investigational methylthioadenosine (MTA) cooperative protein arginine methyltransferase 5 (PRMT5) inhibitor.
IDEAYA Biosciences chief scientific officer Dr Michael White said: “We have a deep understanding of the underlying biological rationale for this combination of a MAT2A inhibitor and an MTA-cooperative PRMT5 inhibitor.
“As presented at AACR 2023, gene expression analysis of hallmark pathways, alternative splicing analysis and retained intron analysis collectively demonstrate that combined pharmacological inhibition of MAT2A and PRMT5 deepens the biological response through maximal pathway suppression.
“The enhanced combination effect was observed selectively in MTAP-null models.”
IDEAYA is also enrolling patients for its Phase II monotherapy expansion cohorts of IDE397 for treating squamous cell non-small cell lung cancer, bladder cancer and oesophagogastric cancer.
Under a clinical trial collaboration and supply agreement, IDEAYA and Amgen will assess the combination of IDE397 and AMG 193 in patients having tumours with MTAP deletion in a Phase I/II study sponsored by Amgen.