Thousand Oaks, California, U.S., October 24, 2026

Amgen announced positive interim Phase 3 results showing that IMDELLTRA® (tarlatamab-dlle), combined with AstraZeneca’s IMFINZI® (durvalumab), reduced the risk of death by 58% in patients with first-line maintenance treatment for extensive-stage small cell lung cancer (ES-SCLC). Findings from the global DeLLphi-305 study demonstrated a median overall survival of 21.1 months with the combination, compared with 12.7 months with durvalumab alone. The results were presented during a Presidential Symposium at the 2026 European Society for Medical Oncology (ESMO) Congress and simultaneously published in The New England Journal of Medicine. The trial enrolled patients whose disease had not progressed following initial treatment with durvalumab, platinum-based chemotherapy and etoposide. These findings could support further investigation of earlier use of tarlatamab in the treatment pathway for this aggressive form of lung cancer, where long-term disease control remains challenging.

DeLLphi-305 Shows Significant Overall Survival Improvement

The Phase 3 DeLLphi-305 study evaluated IMDELLTRA plus IMFINZI against IMFINZI alone as first-line maintenance therapy in patients with ES-SCLC who had not experienced disease progression after initial chemoimmunotherapy. A total of 563 patients were randomized to receive either the combination or durvalumab monotherapy. At a median follow-up of approximately 16 months, the combination reduced the risk of death by 58%, with a hazard ratio of 0.42 and a p-value below 0.001. Median overall survival reached 21.1 months, compared with 12.7 months in the control group. Nearly 80% of patients receiving the combination were alive at one year, compared with 53% receiving durvalumab alone. The findings represent a substantial improvement in survival outcomes in this treatment setting. Benefits were observed across prespecified patient subgroups, including patients with brain or liver metastases, which are often associated with poorer outcomes. The results remain interim data, and continued follow-up will help characterize the durability of the survival benefit.

Combination Therapy Improves Disease Control and Response Rates

The study also demonstrated improvements in progression-free survival and tumour response. At a median follow-up of 13.9 months for the progression-free survival analysis, IMDELLTRA plus IMFINZI reduced the risk of disease progression or death by 66% compared with IMFINZI alone. Median progression-free survival was 7.4 months with the combination, compared with 1.9 months in the control group. The objective response rate was 26.4% among patients receiving the combination, more than six times the 4.1% response rate reported with durvalumab alone. These findings suggest that adding tarlatamab may help patients maintain disease control for longer after initial treatment. The safety profile was consistent with the known profiles of the individual medicines. Grade 3 or higher treatment-related adverse events occurred in 20.9% of patients receiving the combination and 10.8% receiving durvalumab alone. Cytokine release syndrome (CRS) occurred in 49.6% of patients treated with IMDELLTRA, predominantly at Grade 1 or Grade 2 severity. Immune effector cell-associated neurotoxicity syndrome (ICANS) occurred in 1.1%, with no Grade 3 or higher ICANS events reported in this study. The findings underscore the need for appropriate monitoring and management of treatment-related risks.

Advertisement

cGxPJobs Banner

Amgen Advances Tarlatamab Development in Lung Cancer

IMDELLTRA is a bispecific T-cell engager designed to bind DLL3 on tumour cells and CD3 on T cells, bringing immune cells into proximity with cancer cells and promoting tumour-cell destruction. DLL3 is expressed on many small cell lung cancer cells and offers a target for immunotherapy. IMFINZI, whose generic name is durvalumab, is a PD-L1 immune checkpoint inhibitor that helps restore antitumour immune activity. Their combination uses complementary immune mechanisms to extend disease control after initial chemotherapy. Amgen is evaluating tarlatamab across multiple clinical studies and stages of SCLC treatment, including first-line maintenance and previously treated disease. The company said it intends to share the DeLLphi-305 findings with regulatory authorities worldwide. IMDELLTRA is currently indicated in the United States for adults with ES-SCLC whose disease has progressed on or after platinum-based chemotherapy; the first-line maintenance combination described here is investigational. Further regulatory review and clinical follow-up will determine whether the new results translate into an expanded treatment option for patients.

Source: Amgen press release