First-in-Human Trial Shows Promising Results for DLL3-Targeted Antibody-Drug Conjugate SHR-4849 in Relapsed Small Cell Lung Cancer

(Barcelona, Spain Sunday, September 7, 2025 at 4:45 PM CEST / UTC +2) — A first-in-human Phase 1 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 today 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 2 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.

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About the IASLC:
The International Association for the Study of Lung Cancer (IASLC) is the only global organization dedicated solely to the study of lung cancer and other thoracic malignancies. Founded in 1974, the association's membership includes more than 10,000 lung cancer specialists across all disciplines in over 100 countries, forming a global network working together to conquer lung and thoracic cancers worldwide. The association also publishes the Journal of Thoracic Oncology, the primary educational and informational publication for topics relevant to the prevention, detection, diagnosis, and treatment of all thoracic malignancies. Visit www.iaslc.org for more information.

About the WCLC:
The WCLC is the world’s largest meeting dedicated to lung cancer and other thoracic malignancies, attracting nearly 7,000 researchers, physicians, and specialists from more than 100 countries. The goal is to increase awareness, collaboration and understanding of lung cancer, and to help participants implement the latest developments across the globe. The conference will cover a wide range of disciplines and unveil several research studies and clinical trial results. For more information, visit https://wclc.iaslc.org/.