Amgen's Imdelltra Extends Small Cell Lung Cancer Survival to 21 Months

Key points

• The DeLLphi-305 trial demonstrated a 58% reduction in the risk of death for ES-SCLC patients receiving Imdelltra plus Imfinzi as first-line maintenance therapy.
• Median overall survival reached 21.1 months in the combination arm compared to 12.7 months for Imfinzi alone, with nearly 80% of patients alive at one year.
• Progression-free survival improved significantly, with a median of 7.4 months versus 1.9 months, and the risk of disease progression or death dropped by 66%.
• Safety profiles were manageable, with cytokine release syndrome occurring in nearly half of patients but mostly at low grades; monitoring times have been reduced to 1-2 hours in some regions.
• Amgen is expanding Imdelltra’s use into earlier treatment stages, including induction and maintenance settings, potentially addressing 35,000 to 40,000 patients annually.

Background

Small cell lung cancer (SCLC) is an aggressive disease with a median survival of approximately one year, and only about 40% of patients receive second-line therapy. Previous treatments, such as Jazz Pharmaceuticals’ Zepzelca, offered modest improvements, reducing the risk of death by 27% in combination with Roche’s Tecentriq. The current results mark a significant advancement over these prior benchmarks.

How outlets are covering it

Amgen’s Chief Medical Officer Paul Burton described the results as a 'watershed moment' and 'transformational' for SCLC, comparing the impact to Revolution Medicines’ Rasonque in pancreatic cancer. AstraZeneca’s oncology R&D chief Susan Galbraith noted that the five-year survival rate for ES-SCLC is even lower than for pancreatic ductal adenocarcinoma, highlighting the severity of the disease. Lead trial investigator Jacob Sands emphasized that benefits were seen across subgroups, including those with brain or liver metastases. While Amgen and CNBC focused on the potential for Imdelltra to become a 'backbone therapy,' competitors like Zai Lab are developing DLL3-targeted antibody-drug conjugates, such as zocilurtatug pelitecan, which showed high response rates in early trials. Citi analysts suggested this competitor could become a chemo-sparing backbone in future combinations.

Why it matters

The success of Imdelltra in first-line maintenance could redefine the standard of care for ES-SCLC, potentially converting it into a chronic disease for some patients. The drug’s commercial potential is significant, with 2025 global sales of $627 million and a trajectory toward blockbuster status. Additionally, the reduced monitoring requirements and manageable safety profile make the therapy more accessible, while ongoing trials aim to expand its use to earlier stages and limited-stage SCLC.

What to watch

Amgen is evaluating Imdelltra in combination with Imfinzi and chemotherapy as a first-line induction and maintenance therapy in the phase 3 DeLLphi-312 trial. Another trial, DeLLphi-306, will assess its use following chemoradiotherapy in limited-stage SCLC. The company is also exploring combinations with other agents, including Zai Lab’s zocilurtatug pelitecan, to further enhance efficacy. Regulatory submissions are expected as Amgen moves to share these results with global authorities.