A first-in-human Phase I study of SHR-4849 (IDE849), a Delta-like ligand 3 (DLL3)-directed antibody-drug conjugate (ADC), demonstrated manageable safety and early signs of anti-tumor activity in patients with relapsed small cell lung cancer (SCLC).

The results were presented at the International Association for the Study of Lung Cancer 2025 World Conference on Lung Cancer (WCLC).

According to the International Agency for Research on Cancer, there were 2.48 million people diagnosed with lung cancer in 2022. Of those, small cell lung cancer was diagnosed in 11.5% of men and 9.7% of women. Small cell lung cancer has limited treatment options and poor prognosis.

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.

Dr. Linlin Wang and colleagues from the Affiliated Cancer Hospital of Shandong First Medical University treated 54 patients across five dose levels ranging from 0.8 to 4.2 mg/kg. Objective response rate (ORR) among 42 evaluable SCLC patients was 59.5% and disease control rate (DCR) was 90.5%. ORR was 69.2% among patients with at least 12 weeks of follow-up, and 77.8% at the 2.4 mg/kg expansion dose.

The most common treatment-related adverse events 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 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 (RP2D). Further clinical development will assess SHR-4849’s potential 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.

Provided by
International Association for the Study of Lung Cancer