Imdelltra and Imfinzi Combination Cuts Risk of Death 58% in Small-Cell Lung Cancer
Key Facts
Results from a planned interim analysis of the Phase 3 DeLLphi-305 trial showed that adding Imdelltra, whose generic name is tarlatamab, to Imfinzi, or durvalumab, cut the risk of death 58% compared with Imfinzi alone. The result applies to patients with extensive-stage small-cell lung cancer whose disease had not progressed after initial treatment based on Imfinzi and platinum-based chemotherapy and etoposide. Amgen said the hazard ratio for death was 0.42, within a 95% confidence interval of 0.32 to 0.54, with a p-value below 0.001. The analysis was based on a median follow-up of about 16 months. This places the combination in the setting of first-line maintenance therapy, not as a general standalone treatment for advanced lung cancers.
Median overall survival was 21.1 months for those who received the combination, versus 12.7 months for those who received Imfinzi alone, a difference of more than 8 months. AstraZeneca said the estimate showed that 79% of patients in the combination group were alive after one year, compared with 53% in the control group. These figures support the overall-survival result with a direct time-based measure, alongside the relative reduction in the risk of death. The study compared the two specified treatments, with the addition of Imdelltra the difference between the arms. The results do not mean the same benefit applies to patients who did not undergo the specified initial treatment.
The trial included 563 patients who completed initial treatment based on Imfinzi, then were randomly assigned in a 1:1 ratio to receive Imfinzi with tarlatamab or Imfinzi alone. On the progression-free survival endpoint, the combination cut the risk of disease progression or death 66%, with a hazard ratio of 0.34. Median progression-free survival was 7.4 months with the combination, versus 1.9 months with Imfinzi alone, at a median follow-up of 13.9 months. The confirmed objective response rate was also 26.4%, compared with 4.1% in the Imfinzi-alone group. Median duration of response was 12.7 months with the combination, versus 5.6 months in the other group, according to AstraZeneca.
AstraZeneca said the overall-survival and progression-free-survival benefits were consistent across all prespecified subgroups, including patients with brain or liver metastases. Amgen, meanwhile, reported treatment-related adverse events of Grade 3 or higher in 20.9% of patients who received the combination, versus 10.8% with durvalumab alone. Cytokine release syndrome occurred in 49.6% of those who received Imdelltra, with most cases Grade 1 or 2; one Grade 3 case was recorded, at 0.4%. The incidence of immune effector cell-associated neurotoxicity syndrome was 1.1%, with no Grade 3 or higher cases in the trial. The study plan included health monitoring for one to two hours after the first two Imdelltra infusions, extending to 6–8 hours in some regions, including Europe.
The maintenance results follow the U.S. Food and Drug Administration's 2025 approval of Imdelltra for adults with extensive-stage small-cell lung cancer that progresses during or after platinum-based chemotherapy. That approval was based on the DeLLphi-304 study, which compared Imdelltra with standard chemotherapy after a platinum-based treatment line. According to Amgen, Imdelltra cut the risk of death 40% in that study, and median overall survival was 13.6 months versus 8.3 months with chemotherapy. DeLLphi-305 is testing its use at a different stage, after completion of initial treatment with no disease progression, and in combination with Imfinzi. The results were presented in a session at the presidential symposium of the European Society for Medical Oncology's ESMO 2026 Congress in Madrid and published simultaneously in The New England Journal of Medicine.
Amgen said on September 8 that DeLLphi-305 had met its primary endpoint of overall survival in a prespecified interim analysis, adding that it would present the details at an international medical conference and share them with regulators. After the detailed results were announced, Jay Bradner, the company's executive vice president of research and development, artificial intelligence and data, said Amgen was moving “with urgency to share these results with regulators around the world.” The company's stock, listed under the ticker AMGN, closed at $444.63 on October 26, $447.95 on October 27, $451.83 on October 28, $460.73 on October 29 and $466.01 on October 30, according to EL7 data. These closing prices do not establish that the results announcement caused the stock's movement. The company had said the details would be shared with regulators, without specifying in the available information a subsequent date for doing so.