IMDELLTRA Plus Imfinzi Delivers Landmark Overall Survival Benefit in First-Line Extensive-Stage Small Cell Lung Cancer
核心洞察
The Phase 3 DeLLphi-305 trial met its primary endpoint, showing IMDELLTRA (tarlatamab-dlle) plus Imfinzi (durvalumab) significantly improved overall survival versus durvalumab alone in first-line maintenance for ES-SCLC.
The combination also delivered statistically significant and clinically meaningful improvements in the secondary endpoints of progression-free survival and objective response rate.
This marks the first Phase 3 study of a Bispecific T-cell Engager (BiTE) therapy to demonstrate an overall survival benefit in the first-line maintenance setting for ES-SCLC.
Amgen and AstraZeneca announced landmark results from the Phase 3 DeLLphi-305 study, which met its primary endpoint at a pre-specified interim analysis, demonstrating a statistically significant and clinically meaningful improvement in overall survival (OS) with IMDELLTRA (tarlatamab-dlle) in combination with AstraZeneca's Imfinzi (durvalumab) compared to durvalumab alone. The study evaluated IMDELLTRA as a first-line maintenance treatment for people with extensive-stage small cell lung cancer (搜索) (ES-SCLC) whose disease had not progressed following initial treatment with durvalumab, platinum-based chemotherapy and etoposide.
The study also demonstrated a statistically significant and clinically meaningful improvement in progression-free survival (PFS) and objective response rate (ORR) among patients treated with IMDELLTRA in combination with durvalumab. This marks the first Phase 3 study including a Bispecific T-cell Engager (BiTE) therapy to demonstrate an overall survival benefit in the first-line maintenance setting for ES-SCLC.
"IMDELLTRA has already revolutionized the standard of survival for patients with extensive stage small cell lung cancer (搜索) whose disease progressed on or after prior treatment. These landmark results from DeLLphi-305 suggest IMDELLTRA will further revolutionize the standard for survival earlier in the treatment journey and meaningfully shift the treatment paradigm for people facing this devastating disease," said Jay Bradner, M.D., executive vice president, Research and Development, Artificial Intelligence and Data at Amgen.
Susan Galbraith, Executive Vice President, Oncology Haematology R&D, AstraZeneca, added: "These results show that Imfinzi-based induction therapy followed by maintenance treatment with Imfinzi plus tarlatamab demonstrates an unprecedented improvement in overall survival for patients with this highly aggressive form of lung cancer."
Unmet Need in Extensive-Stage Small Cell Lung Cancer
SCLC is one of the most aggressive forms of lung cancer, accounting for approximately 13-15% of the more than 2.6 million lung cancer cases diagnosed worldwide each year. About two-thirds of SCLC patients are diagnosed with ES-SCLC, in which the cancer has spread widely through the lung or to other parts of the body. In 2026, an estimated 195,000 people globally will be treated for ES-SCLC.
Despite advances in the treatment of ES-SCLC, outcomes remain poor, with a median survival of approximately one year from the start of first-line maintenance treatment and only about 40% of patients receiving second-line therapy. While immune checkpoint inhibitors such as Imfinzi have led to significant improvements in OS, establishing a first-line standard of care, many patients still experience disease progression due to the aggressive nature of the disease.
"Given the aggressive nature of small cell lung cancer (搜索), many patients quickly relapse on current therapy and never reach second-line treatment. These patients do not have time to wait, making substantial progress in the first-line setting critically important," said Jacob Sands, MD, Associate Chief of the Lowe Center for Thoracic Oncology at Dana-Farber Cancer Institute. "In my career treating people with extensive stage small cell lung cancer, these are among the most compelling survival results I have seen, indicating the potential to reshape the natural history of small cell lung cancer."
Study Design
The DeLLphi-305 trial is sponsored by Amgen, with partial funding and durvalumab provided by AstraZeneca. It is a global Phase 3, randomized, open-label clinical trial evaluating the efficacy and safety of IMDELLTRA in combination with durvalumab compared to durvalumab alone as first-line maintenance treatment for patients with ES-SCLC who had not progressed following treatment with durvalumab, platinum-based chemotherapy and etoposide.
Five hundred and sixty-three patients who completed initial treatment with durvalumab, platinum-based chemotherapy and etoposide were randomized 1:1 to receive either IMDELLTRA in combination with durvalumab or durvalumab alone until progression or unacceptable toxicity. The trial included patients with both treated and untreated asymptomatic brain metastases at baseline. The primary outcome measure of the trial is OS, with secondary endpoints including PFS and ORR.
Safety Profile
Overall, the safety profile of IMDELLTRA in combination with durvalumab was consistent with the known safety profiles of the individual medicines. No new or unexpected safety signals were identified in DeLLphi-305. The study design included monitoring in a healthcare setting for 1 to 2 hours (6 to 8 hours in certain regions including Europe) following IMDELLTRA infusion on Cycle 1 Day 1 and Cycle 1 Day 8.
Mechanism of Action
IMDELLTRA is a first-in-class targeted immunotherapy engineered by Amgen researchers to bind to both DLL3 (搜索) on tumor cells and CD3 (搜索) on T cells, thereby activating T cells to kill DLL3-expressing SCLC cells. This results in the formation of a cytolytic synapse with lysis of the cancer cell. DLL3 is a protein that is expressed on the surface of SCLC cells in approximately 85-96% of patients with SCLC, but is minimally expressed on healthy cells, making it an attractive therapeutic target.
Imfinzi (durvalumab) is a human monoclonal antibody that binds to the PD-L1 (搜索) protein and blocks the interaction of PD-L1 with the PD-1 and CD80 proteins, countering the tumor's immune-evading tactics and releasing the inhibition of immune responses.
Next Steps
Amgen plans to present detailed data from DeLLphi-305 at an upcoming international medical congress and share it with regulatory authorities. Building on the DeLLphi-303 trial, which showed very encouraging efficacy and tolerability results for IMDELLTRA in combination with anti-PD-L1 (搜索) checkpoint inhibitors in the treatment of first-line ES-SCLC, DeLLphi-305 was designed to evaluate IMDELLTRA earlier in the course of disease, where more patients with SCLC may have the opportunity to benefit.