Cancer Drug Maker IDEAYA Biosciences Starts First Patient Trial For New Combo Therapy, Tests New Drug Pair Aimed At Hard-To-Treat Cancers

IDEAYA Biosciences, Inc. (NASDAQ:IDYA), a precision medicine oncology company committed to the discovery and development of targeted therapeutics, announced first-patient-in for a Phase 1 clinical trial combination study to evaluate IDE849, a potential first-in-class delta-like ligand 3 (DLL3)-targeting Topo-I-payload antibody drug conjugate (ADC) program, and IDE161, a potential first-in-class poly(ADP-ribose) glycohydrolase (PARG) inhibitor. The Phase 1 combination study will be evaluated in DLL3 upregulated solid tumor indications, including small cell lung cancer (SCLC), neuroendocrine tumors (NETs), neuroendocrine carcinomas (NECs), and melanoma. "We are excited about the progress in our Phase 1 IDE849 monotherapy study to determine the RP2D and to initiate a registrational study by year-end, and the advancement of our wholly owned first-in-class clinical combination of IDE849 and IDE161 in DLL3 upregulated solid tumor indications," said Yujiro S. Hata, President and Chief Executive Officer, IDEAYA Biosciences. "We are leveraging our deep scientific expertise in DNA damage repair to enable this rational combination with IDE161, with the goal of inducing accumulation of TOP1 lesions to enhance the clinical efficacy and durability of our proprietary TOP1-payload ADCs, including IDE849 and IDE034, a Phase 1 B7H3/PTK7 bispecific TOP1 ADC," said Michael White, Ph.D., Chief Scientific Officer, IDEAYA Biosciences.IDEAYA is advancing a multi-site global Phase 1 clinical trial for IDE849 in DLL3 upregulated solid tumor indications, including SCLC, NETs, and NECs, and melanoma (NCT07174583). The study will be enrolling patients globally, including in North America, Europe, Australia, South America, and Asia. In this ongoing Phase 1 dose escalation study, IDE849 is currently evaluating a 3.5 mg/kg IV dose once every 3-weeks (Q3W). Next, to determine the recommended Phase 2 dose (RP2D), IDEAYA is also enrolling patients in a IDE849 expansion cohort at the 2.4 mg/kg IV dose Q3W, where multiple partial responses (PRs) have been observed by RECIST 1.1, including 3 PRs out of 4 SCLC patients pre-treated with IMDELLTRA® (tarlatamab-dlle). The preliminary safety and efficacy profile observed to date in the IDEAYA sponsored study is consistent with the clinical data presented by our China-region partner Jiangsu Hengrui Pharmaceuticals Co. Ltd., at the IASLC World Conference on Lung Cancer 2025 (WCLC 2025).In addition, IDE849 is being evaluated in a clinical combination with IDEAYA's potential first-in-class Phase 1 PARG inhibitor, IDE161. IDEAYA has presented preclinical combination mechanism and synergy efficacy data of IDE161/PARG with TOP1-payload based ADCs at WCLC 2025. IDE161 prevents the removal of poly(ADP-ribose) chains generated by PARP during the DNA damage response, leading to persistent PARylation and impaired resolution of DNA repair complexes. Together with TOP1-payload ADCs, this unique mechanism-of-action results in sustained TOP1 cleavage complexes and the accumulation of DNA damage that delivers enhanced anti-tumor activity. We believe this potential first-in-class combination has the potential to enhance durability of IDEAYA's TOP1-payload based ADC pipeline, including IDE849 and IDE034 (Phase 1 B7H3/PTK7 Bispecific TOP1 ADC).DLL3 has been reported to be upregulated in multiple solid tumor types, including in SCLC, NETs, NSCLC, melanoma, among others. DLL3 has limited extracellular expression in normal tissues, making it a promising potential therapeutic target in these solid tumors, for which there remains significant unmet medical need.