Antibody drug shows promise against lung cancer in human trial

New Delhi: A team of researchers in China has led a first-in-human trial of an antibody drug that may provide better treatment for people with relapsed small-cell lung cancer (SCLC).

SCLC is a fast-growing, highly malignant lung cancer. 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 per cent of men and 9.7 per cent of women. Small-cell lung cancer has limited treatment options and a poor prognosis.

The 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-tumour activity in patients with relapsed SCLC.

SHR-4849 consists of a humanised 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 in China 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 per cent, and disease control rate (DCR) was 90.5 per cent. ORR was 69.2 per cent among patients with at least 12 weeks of follow-up, and 77.8 per cent 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 favourable safety.