Amgen and AstraZeneca’s IMDELLTRA-IMFINZI Improves SCLC Survival

Thousand Oaks, California, USA, September 8, 2026

Phase 3 Trial Shows Significant Overall Survival Benefit

The DeLLphi-305 study is a global, randomized, open-label Phase 3 trial evaluating tarlatamab in combination with durvalumab versus durvalumab alone in patients with extensive-stage small cell lung cancer who had not previously received systemic therapy. The trial enrolled 563 patients, providing a substantial evaluation of whether tarlatamab could improve outcomes when introduced in the first-line treatment setting. The combination achieved the trial’s primary endpoint, demonstrating a statistically significant improvement in overall survival. The treatment produced a hazard ratio of 0.73, representing a 27% reduction in the risk of death compared with durvalumab alone. Median overall survival was approximately 13.7 months with the combination compared with 10.5 months with durvalumab alone. The combination also demonstrated improvements in additional efficacy measures, including progression-free survival (PFS) and objective response rate (ORR). These findings strengthen the clinical rationale for incorporating DLL3-directed therapy into first-line treatment strategies for extensive-stage small cell lung cancer.

Tarlatamab and Durvalumab Use Complementary Immune Mechanisms

Tarlatamab is a bispecific T-cell engager designed to bind DLL3 on tumor cells and CD3 on T cells, bringing immune cells into close proximity with malignant cells and promoting targeted tumor-cell killing. DLL3 is highly expressed in small cell lung cancer, making it an important target for the development of novel therapies. Durvalumab, AstraZeneca’s PD-L1 inhibitor marketed as IMFINZI, works through a complementary mechanism by blocking PD-L1-mediated immune suppression. The combination is designed to produce coordinated immune activity, with tarlatamab recruiting T cells to DLL3-positive cancer cells while durvalumab helps restore immune-cell activity by inhibiting the PD-L1 pathway. The Phase 3 findings therefore provide clinical evidence supporting a dual immunotherapy approach in ES-SCLC. This is particularly significant because extensive-stage small cell lung cancer is characterized by rapid progression and remains an area of considerable unmet medical need despite advances in first-line immunochemotherapy.

Results Could Expand Tarlatamab Into First-Line Treatment

The positive DeLLphi-305 results build on the existing development of tarlatamab, which is already approved in the United States for certain patients with extensive-stage small cell lung cancer whose disease has progressed following platinum-based chemotherapy. Demonstrating an overall survival benefit in the first-line setting could significantly expand the potential clinical role of the DLL3-directed therapy. Amgen and AstraZeneca plan to discuss the findings with global regulatory authorities and determine the next steps toward potential regulatory submissions. Additional analyses will help characterize the durability of the survival benefit, safety profile and patient populations that may derive the greatest benefit from the combination. Importantly, IMDELLTRA in combination with IMFINZI is not currently approved for first-line ES-SCLC, and the Phase 3 findings remain subject to regulatory review. Nevertheless, the results mark a major milestone for the program and provide evidence that targeting DLL3 together with PD-L1 may offer a new therapeutic strategy for patients with newly diagnosed extensive-stage disease. If supported by regulatory review, the regimen could represent an important evolution in the treatment of small cell lung cancer, particularly for patients who need more effective approaches to prolong survival from the outset of treatment.

Source: Amgen, AstraZeneca press release