IDEAYA Biosciences (NASDAQ:IDYA), a leading precision medicine oncology company, today announced the first-patient-in (FPI) for its Phase 1 clinical trial evaluating the combination of IDE849 and IDE161.
The study is designed to assess the safety, tolerability, and preliminary efficacy of this first-in-class combination in patients with solid tumors characterized by delta-like ligand 3 (DLL3) upregulation, including small cell lung cancer (SCLC), neuroendocrine tumors (NETs), neuroendocrine carcinomas (NECs), and melanoma.
IDE849 is a potential first-in-class DLL3-targeting antibody-drug conjugate (ADC) featuring a Topoisomerase-I (TOP1) payload.
IDE161 is a potent, selective, potential first-in-class small molecule inhibitor of poly(ADP-ribose) glycohydrolase (PARG).
The rationale for the combination is based on preclinical models suggesting that PARG inhibition can induce the accumulation of TOP1-DNA covalent complexes, thereby sensitizing tumors to the cytotoxic effects of TOP1-payload ADCs and potentially extending the duration of response.
The initiation of the combination study follows encouraging early results from the ongoing global IDE849 Phase 1 monotherapy program.
In a 2.4 mg/kg IV Q3W expansion cohort, multiple partial responses were observed according to RECIST v1.1 criteria.
Notably, these included three partial responses out of four SCLC patients who had previously progressed on Amgen’s IMDELLTRA® (tarlatamab-dlle).
The monotherapy program is currently advancing through dose escalation, evaluating a 3.5 mg/kg IV Q3W dose level to determine the recommended Phase 2 dose (RP2D).