FDA Clears IND for Novel DLL3-Targeted ADC in Solid Tumors
The FDA cleared the investigational new drug application of IDE849, a potential first-in-class DLL3-targeted antibody-drug conjugate for solid tumors.
US FDA
- The FDA has cleared the investigational new drug (IND) application for IDE849 (SHR-4849) in solid tumor treatment.
- IDE849 is a first-in-class delta-like ligand 3 (DLL3) topoisomerase-I (TOP1) antibody-drug conjugate (ADC).
- With this clearance, a phase 1 study (NCT06443489) will begin.
The IND for the first-in-class ADC IDE849 has been cleared by the FDA, paving the way for a phase 1 study to investigate the agent in solid tumors.
"We are excited to advance IDE849, a potential first-in-class DLL3 TOP1 ADC, into a phase 1 study in the US. DLL3 is upregulated in multiple solid tumor types, including small cell lung cancer (SCLC), neuroendocrine tumors (NETs), non–small cell lung cancer (NSCLC), melanoma, among other solid tumors, highlighting the potential to have a pipeline in a single asset. We look forward to the IDE849 clinical data update in SCLC at a medical conference in Q3 2025, including at multiple expansion doses," said Yujiro S. Hata, president and chief executive officer, IDEAYA Biosciences, in a press release.
IDE849 is a DLL3-targeting ADC with a TOP1 payload. Along with its upregulation in certain tumor types, DLL3 has limited extracellular expression in normal tissues.
In the phase 1 study evaluating IDE849 so far, the agent has reached therapeutic does, and multiple partial responses have been reported as of the data cut-off date of December 10, 2024. Regarding safety, the treatment-related adverse events (TRAEs) were primarily grade 1 or 2. The most common TRAEs were decreased white blood cell count, anemia, decreased neutrophil count, decreased platelet count, and nausea.
Phase 1 dose escalation is continuing, with no drug-related discontinuations reported and no maximum tolerated dose yet reached.
Along with the phase 1 study to investigate IDE849, IDEAYA Biosciences is also planning to evaluate the agent in combination with IDE161, a potential first-in-class PARG inhibitor.
“In addition, IDE849 aligns with our strategy to develop rational combination therapies, particularly with our potential first-in-class phase 1 PARG inhibitor IDE161, where we have generated preclinical combination data with TOP1-based ADCs that demonstrates combination synergy and enhanced durability," said Darrin M. Beaupre, MD, PhD, chief medical officer, IDEAYA Biosciences, in the press release.
