A first-in-human phase I study of SHR-4849 (IDE849), a Delta-like ligand 3 (DLL3)-directed antibody-drug conjugate, demonstrated manageable safety and early signs of antitumor activity in patients with relapsed small cell lung cancer (SCLC). The results were presented at the International Association for the Study of Lung Cancer (IASLC) 2025 World Conference on Lung Cancer (WCLC; Abstract OA06.01).
SHR-4849 consists of a humanized anti-DLL3 IgG1 monoclonal antibody linked to a DNA topoisomerase I inhibitor via a cleavable linker. Given the high expression of DLL3 in SCLC, the drug is being explored as a targeted treatment option for patients with limited therapeutic alternatives.
Linlin Wang, MD, and colleagues, of the Affiliated Cancer Hospital of Shandong First Medical University, treated 54 patients with the agent across five dose levels (ranging from 0.8 to 4.2 mg/kg). The objective response rate among 42 evaluable patients was 59.5%, and the disease control rate was 90.5%. The objective response rate was 69.2% among patients with at least 12 weeks of follow-up, and it was 77.8% at the 2.4-mg/kg expansion dose.
The most common treatment-related adverse events in patients who received SHR-4849 included decreased white blood cell count, anemia, neutropenia, and nausea. No treatment-related adverse events led to dose discontinuation or death.
The study used a dose-escalation and dose-expansion approach, identifying preliminary efficacy at multiple dose levels with favorable safety. No dose-limiting toxicities were observed at doses below 4.2 mg/kg. Plasma exposure of the free toxin remained low across all doses.
Dose expansion is ongoing to determine the recommended phase II dose. Further clinical development will assess the potential of SHR-4849 as a therapeutic option for DLL3-expressing SCLC, Dr. Wang reported.
“These encouraging early data support further investigation of SHR-4849 as a potential treatment for patients with DLL3-positive relapsed SCLC,” said Dr. Wang.
Disclosure: For full disclosures of the study authors, visit cattendee.abstractsonline.com.
