Amgen's Imdelltra With Imfinzi Improves Survival in Phase 3 First-Line SCLC Trial

Amgen said on September 8 that its Phase 3 DeLLphi-305 trial showed a statistically significant improvement in overall survival when its drug Imdelltra (tarlatamab-dlle) was added to AstraZeneca's Imfinzi (durvalumab) as first-line maintenance treatment for extensive stage small cell lung cancer (ES-SCLC), according to the company's announcement.

The trial met its primary endpoint at a pre-specified interim analysis, Amgen said. It also met its secondary endpoints, showing statistically significant improvements in progression-free survival and objective response rate. The company did not disclose hazard ratios, median survival times or response rates in the announcement, and the results have not yet been presented at a meeting or published in a journal.

The DeLLphi-305 trial

DeLLphi-305 is a global, randomized, open-label Phase 3 trial sponsored by Amgen, with partial funding and durvalumab supplied by AstraZeneca. It enrolled 563 patients whose cancer had not progressed after initial treatment with durvalumab, platinum-based chemotherapy and etoposide. They were randomized 1:1 to receive Imdelltra plus durvalumab or durvalumab alone until their disease progressed or side effects became unacceptable.

The trial included patients with both treated and untreated brain metastases that were not causing symptoms at baseline. Patients were monitored in a healthcare setting for 1 to 2 hours after the Imdelltra infusions on days 1 and 8 of the first cycle, or 6 to 8 hours in some regions including Europe, the company said.

Imdelltra is a bispecific T-cell engager, or BiTE, that binds to DLL3 on tumor cells and CD3 on T cells, directing the immune cells to attack the cancer. Amgen said DeLLphi-305 is the first Phase 3 study including a BiTE therapy to show an overall survival benefit in first-line maintenance for ES-SCLC.

Safety and company statements

The safety profile of the combination was consistent with the known profiles of the two medicines, and no new or unexpected safety signals were identified, according to Amgen. Imdelltra's U.S. label carries a boxed warning for cytokine release syndrome and neurologic toxicity, including immune effector cell-associated neurotoxicity syndrome.

"Despite clinical advances, extensive stage small cell lung cancer remains one of the most aggressive and difficult-to-treat cancers, and substantial improvements in survival are rare, underscoring the importance of these findings," said Jay Bradner, Amgen's executive vice president of research and development, artificial intelligence and data.

Jacob Sands, associate chief of the Lowe Center for Thoracic Oncology at Dana-Farber Cancer Institute, said in the company's release that many patients "quickly relapse on current therapy and never reach second-line treatment."

Amgen cited figures that SCLC accounts for about 13% to 15% of the more than 2.6 million lung cancer cases diagnosed worldwide each year, and that median survival is about one year from the start of first-line maintenance treatment, with only about 40% of patients receiving second-line therapy.

Where Imdelltra stands

Imdelltra is already approved in the United States for adults with ES-SCLC whose disease has progressed on or after platinum-based chemotherapy. The American Journal of Managed Care reported that the FDA converted that label from accelerated to traditional approval in November 2025, based on the Phase 3 DeLLphi-304 trial in the second-line setting.

The first-line maintenance use tested in DeLLphi-305 is not approved. Amgen said it plans to present detailed data from the trial at an upcoming international medical congress and to share the results with regulatory authorities. The company is also running other studies of tarlatamab, including the Phase 3 DeLLphi-312 trial of the drug with durvalumab, carboplatin and etoposide as induction and maintenance therapy in first-line ES-SCLC.