Small cell lung cancer (SCLC) accounts for 10-15% of all lung cancer cases annually, with 250,000 incident cases diagnosed every year and 200,000 deaths occurring. With such a high healthcare burden, rapid advancements have been made with the advent of programmed cell death protein-1 checkpoint inhibition and immunotherapy, although they have only been proven successful in the first-line paradigm. Unlike non-small cell lung cancer (NSCLC), the treatment options for SCLC are more limited, as it is more aggressive and develops resistance to available treatments rapidly. One of the current standards of care (SOC) is the use of platinum-based chemotherapy such as cisplatin in combination with Roche’s Tecentriq or AstraZeneca’s Imfinzi in the first-line treatment for extensive-stage SCLC (ES-SCLC). Following treatment, many patients with NSCLC will develop platinum resistance through strengthened DNA-repair capabilities and reduced chemotherapy uptake in the cancerous cells.

Amgen’s Imdelltra, a bispecific T-cell engager (BiTE) that targets Delta-like canonical Notch ligand 3 (DLL3) and cluster of differentiation 3 (CD3) receptors, received US Food and Drug Administration approval for the treatment of patients with ES-SCLC following disease progression or following platinum-based chemotherapy, based on results from the DeLLphi-301 trial. While the approval is a historic event for the BiTE drug class in solid tumours, the market share opportunity is restricted as DeLLphi-301 was a Phase II trial with only one arm and no comparator. Results from the American Society of Clinical Oncology 2025 have shown the latest in Imdelltra’s clinical results from the DeLLphi-304 trial.

DeLLphi-304 enrolled 254 patients receiving Imdelltra and 255 receiving one of the following: topotecan, amrubicin, or Jazz Pharmaceutical’s Zepzelca. Zepzelca and topotecan are preferred systemic treatment options for SCLC. Imdelltra was found to increase overall survival by 5.3 months (hazard ratio: 0.60, P<0.001) and increase median progression-free survival. There was also a large difference in grade 3 treatment-related adverse events, with Imdelltra reducing the rate by 35% compared to the control arm. Absent any competing immunotherapies with a preferred National Comprehensive Cancer Network opinion, Imdelltra is expected to be an attractive option for many patients looking to enhance their care. The annual cost of Imdelltra therapy totals $167,600 per patient. As a result, Imdelltra will likely struggle to receive reimbursement outside of the US.