Phase 3 DeLLphi-305 Study Delivered Highly Significant and Clinically Meaningful Overall Survival Benefit Versus Durvalumab Alone

Study Also Met Secondary Progression-Free Survival and Objective Response Rate Endpoints

THOUSAND OAKS, Calif., Sept. 8, 2026 /PRNewswire/ -- Amgen (NASDAQ: AMGN) today 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 with IMDELLTRA® (tarlatamab-dlle) in combination with AstraZeneca's Imfinzi® (durvalumab) compared to durvalumab alone. This study tested IMDELLTRA as a first-line maintenance treatment for people with extensive stage small cell lung cancer (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.

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.

"IMDELLTRA has already revolutionized the standard of survival for patients with extensive stage small cell lung cancer 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. "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."

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.

"Given the aggressive nature of small cell lung cancer, 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. DeLLphi-305 represents an unprecedented milestone and suggests we may be entering a new era where meaningfully longer survival is possible for more patients."

Following the U.S. Food and Drug Administration (FDA) approval of IMDELLTRA for adults with ES-SCLC whose disease has progressed on or after platinum-based chemotherapy, the robust global DeLLphi clinical trial program has continued to evaluate its potential across earlier stages of disease and lines of treatment, both as a monotherapy and in combination regimens. Building on the DeLLphi-303 trial, which showed very encouraging efficacy and tolerability results for IMDELLTRA in combination with anti-PD-L1 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.

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.1-3 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.4-7

Amgen plans to present detailed data from DeLLphi-305 at an upcoming international medical congress and share it with regulatory authorities.

About the Phase 3 DeLLphi-305 Study

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. Following IMDELLTRA infusion on Cycle 1 Day 1 and Cycle 1 Day 8, patients were monitored in a healthcare setting for 1 to 2 hours (6 to 8 hours in certain regions including Europe). The trial included patients with both treated and untreated asymptomatic brain metastases at baseline. The primary outcome measure of the trial is OS. Secondary endpoints include progression-free survival (PFS) and objective response rate (ORR).8

About Tarlatamab Clinical Trials 

Tarlatamab is being investigated in multiple studies including DeLLphi-303, a Phase 1b study investigating tarlatamab in combination with standard-of-care (SOC) therapies in first-line ES-SCLC; DeLLphi-304, a randomized Phase 3 study comparing tarlatamab monotherapy with SOC chemotherapy in second-line treatment of SCLC; DeLLphi-305, a randomized Phase 3 study comparing tarlatamab in combination with durvalumab vs. durvalumab alone as first-line maintenance treatment in ES-SCLC; DeLLphi-306, a randomized placebo-controlled Phase 3 study of tarlatamab following concurrent chemoradiotherapy in limited-stage SCLC; DeLLphi-308, a Phase 1b study evaluating subcutaneous tarlatamab in second-line or later ES-SCLC; DeLLphi-309, a Phase 2 study evaluating alternative intravenous dosing regimens with tarlatamab in second-line ES-SCLC; DeLLphi-310, a Phase 1b study of tarlatamab in combination with YL201 with or without durvalumab in patients with ES-SCLC; DeLLphi-311, a Phase 1b study of tarlatamab in combination with etakafusp alfa (AB248), a novel CD8+ T-cell selective interleukin-2 (IL-2), in patients with ES-SCLC; DeLLphi-312, a randomized Phase 3 study evaluating tarlatamab in combination with durvalumab, carboplatin and etoposide as an induction and maintenance therapy in first-line treatment of ES-SCLC; DeLLphi-313, a Phase 1b study of tarlatamab in combination with zocilurtatug pelitecan, a DLL3 targeting antibody drug conjugate, with and without durvalumab in patients with ES-SCLC, and DeLLphi-315, a Phase 3 study of subcutaneous tarlatamab in patients with second-line ES-SCLC.9

For more information, please visit www.tarlatamabclinicaltrials.com.

About IMDELLTRA® (tarlatamab-dlle) 

IMDELLTRA is a first-in-class targeted immunotherapy engineered by Amgen researchers to bind to both DLL3 on tumor cells and CD3 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.10,11 DLL3 is a protein that is expressed on the surface of SCLC cells in ~85-96% of patients with SCLC, but is minimally expressed on healthy cells, making it an exciting target.12,13

U.S. INDICATION

IMDELLTRA® (tarlatamab-dlle) is indicated for the treatment of adult patients with extensive stage small cell lung cancer (ES-SCLC) with disease progression on or after platinum-based chemotherapy. 

IMDELLTRA IMPORTANT SAFETY INFORMATION

WARNING: CYTOKINE RELEASE SYNDROME and NEUROLOGIC TOXICITY including IMMUNE EFFECTOR CELL-ASSOCIATED NEUROTOXICITY SYNDROME

- Cytokine release syndrome (CRS), including life-threatening or fatal reactions, can occur in patients receiving IMDELLTRA®. Initiate treatment with IMDELLTRA® using the step-up dosing schedule to reduce the incidence and severity of CRS. Withhold IMDELLTRA® until CRS resolves or permanently discontinue based on severity. 

- Neurologic toxicity and immune effector cell-associated neurotoxicity syndrome (ICANS), including life-threatening or fatal reactions, can occur in patients receiving IMDELLTRA®. Monitor patients for signs and symptoms of neurologic toxicity, including ICANS, during treatment and treat promptly. Withhold IMDELLTRA® until ICANS resolves or permanently discontinue based on severity.

WARNINGS AND PRECAUTIONS

- Cytokine Release Syndrome (CRS): IMDELLTRA® can cause CRS including life-threatening or fatal reactions. In the pooled safety population, CRS occurred in 57% (268/473) of patients who received IMDELLTRA®, including 39% Grade 1, 15% Grade 2, 1.7% Grade 3 and 0.2% Grade 4. Recurrent CRS occurred in 24% of IMDELLTRA®-treated patients including 20% Grade 1 and 3.4% Grade 2; one patient experienced recurrent Grade 3.

Among the 268 patients who experienced CRS, 73% had CRS after the first dose, 60% had CRS after the second dose, and 15% had CRS following the third or later dose. Following the Cycle 1 Day 1, Day 8, Day 15 infusions, 24%, 8%, and 1% of patients experienced Grade ≥ 2 CRS, respectively. From Cycle 2 onwards, 1.5% of patients experienced Grade ≥ 2 CRS. Of the patients who experienced CRS, 31% received steroids and 10% required tocilizumab.