The IMDELLTRA Imfinzi combination has produced a landmark overall survival benefit in patients with extensive-stage small cell lung cancer (ES-SCLC), Amgen announced on September 8, 2026. The Thousand Oaks, California-based biotechnology company (NASDAQ: AMGN) reported that its Phase 3 DeLLphi-305 study met its primary endpoint at a pre-specified interim analysis, showing a statistically significant and clinically meaningful improvement in overall survival (OS) for IMDELLTRA (tarlatamab-dlle) combined with AstraZeneca’s Imfinzi (durvalumab) versus durvalumab alone.
DeLLphi-305 tested IMDELLTRA as a first-line maintenance treatment for people with ES-SCLC whose disease had noht progressed following initial treatment with durvalumab, platinum-based chemotherapy and etoposide. Beyond the primary survival finding, the trial also delivered statistically significant and clinically meaningful gains in progression-free survival (PFS) and objective response rate (ORR) for patients receiving the IMDELLTRA Imfinzi combination compared with durvalumab monotherapy.
Amgen said the safety profile of the combination regimen was consistent with the known safety profiles of the two individual medicines, and no new or unexpected safety signals emerged during the study. The trial protocol called for patients to be monitored in a healthcare setting for one to two hours after IMDELLTRA infusions on Cycle 1 Day 1 and Cycle 1 Day 8, extending to six to eight hours in certain regions, including Europe.
Jay Bradner, M.D., executive vice president of Research and Development, Artificial Intelligence and Data at Amgen, said the medicine has already changed survival expectations for patients whose ES-SCLC progressed after prior treatment, and that the new DeLLphi-305 findings point toward a further shift in the treatment paradigm earlier in the disease course. He noted that meaningful survival improvements remain rare in this aggressive cancer type, which underscores the significance of the interim results.
IMDELLTRA Imfinzi Combination Trial Design: Inside the DeLLphi-305 Study
DeLLphi-305 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, according to Amgen. The randomized, open-label, global study is sponsored by Amgen, with partial funding and durvalumab supplied by AstraZeneca.
The trial enrolled 563 patients who had completed initial treatment with durvalumab, platinum-based chemotherapy and etoposide without disease progression. Participants were randomized 1:1 to receive either the IMDELLTRA Imfinzi combination or durvalumab alone until disease progression or unacceptable toxicity. Notably, the study population included patients with both treated and untreated asymptomatic brain metastases at baseline, broadening its relevance to real-world ES-SCLC populations. The table below summarizes the core design elements as disclosed in Amgen’s announcement.
| Trial Element | Detail |
|---|---|
| Study name | DeLLphi-305 (Phase 3, randomized, open-label) |
| Sponsor | Amgen, with partial funding and durvalumab supplied by AstraZeneca |
| Patients randomized | 563, in a 1:1 ratio |
| Treatment arms | IMDELLTRA + durvalumab vs. durvalumab alone |
| Setting | First-line maintenance, extensive-stage small cell lung cancer |
| Prior therapy required | Durvalumab, platinum-based chemotherapy and etoposide, without progression |
| Primary endpoint | Overall survival (OS) |
| Secondary endpoints | Progression-free survival (PFS); objective response rate (ORR) |
| Brain metastases | Treated and untreated asymptomatic cases included at baseline |
| Registry identifier | ClinicalTrials.gov NCT06211036 |
Amgen did not disclose specific hazard ratios, median survival figures, or percentage-point improvements for OS, PFS, or ORR in the September 8 announcement; the company said detailed data will be presented at an upcoming international medical congress and shared with regulatory authorities.
Building on the earlier DeLLphi-303 trial, which showed encouraging efficacy and tolerability when IMDELLTRA was combined with anti-PD-L1 checkpoint inhibitors in first-line ES-SCLC, DeLLphi-305 was designed to test the IMDELLTRA Imfinzi combination even earlier in the disease course, where a larger pool of patients could potentially benefit.
IMDELLTRA Imfinzi Combination Safety Profile and Monitoring Protocol
Because IMDELLTRA carries a boxed warning for cytokine release syndrome (CRS) and neurologic toxicity, including immune effector cell-associated neurotoxicity syndrome (ICANS), Amgen’s release reiterated the monitoring steps built into DeLLphi-305. Patients were observed in a healthcare setting following the Cycle 1 Day 1 and Cycle 1 Day 8 infusions, for one to two hours in most regions and six to eight hours in certain regions such as Europe.
In IMDELLTRA’s broader pooled safety population of 473 patients across the DeLLphi-300, DeLLphi-301 and DeLLphi-304 trials, CRS occurred in 57% of patients, and neurologic toxicity occurred in 65%, with Grade 3 or higher neurologic events in 7%. The table below lists the most common adverse reactions reported at the approved monotherapy dose, drawn from IMDELLTRA’s prescribing information as referenced in Amgen’s materials.
| Adverse Reaction (Pooled Safety Population, n=473) | Incidence (All Grades) |
|---|---|
| Cytokine release syndrome (CRS) | 57% |
| Fatigue | 48% |
| Decreased appetite | 38% |
| Dysgeusia (taste alteration) | 34% |
| Pyrexia (fever) | 33% |
| Constipation | 31% |
| Musculoskeletal pain | 31% |
| Nausea | 25% |
Amgen’s release stresses that IMDELLTRA must be administered by a qualified healthcare professional equipped to manage severe reactions, with recommended step-up dosing, pre- and post-infusion concomitant medications, and extended observation windows of 22 to 24 hours following the first two infusions to reduce CRS and ICANS risk.
IMDELLTRA Imfinzi Combination Expert and Clinical Reaction
Jacob Sands, MD, Associate Chief of the Lowe Center for Thoracic Oncology at Dana-Farber Cancer Institute, called the DeLLphi-305 findings among the most compelling survival results he has observed in treating ES-SCLC, given how quickly patients with this aggressive cancer often relapse before reaching second-line therapy. He described the data as an unprecedented milestone that could reshape the natural history of small cell lung cancer, suggesting more patients may achieve meaningfully longer survival with the IMDELLTRA Imfinzi combination than with durvalumab alone.
That urgency reflects the underlying disease burden. SCLC accounts for roughly 13% to 15% of the more than 2.6 million lung cancer cases diagnosed worldwide each year, and outcomes in extensive-stage disease remain poor despite recent treatment advances.
| SCLC Disease Burden Metric | Reported Figure |
|---|---|
| Share of global lung cancer cases that are SCLC | Approximately 13%–15% |
| Annual global lung cancer cases (all types) | More than 2.6 million |
| Median survival from start of first-line maintenance | Approximately one year |
| Patients who reach second-line therapy | Only about 40% |
| DLL3 expression on SCLC tumor cells | Approximately 85%–96% of patients |
IMDELLTRA Imfinzi Combination: Next Steps, Pipeline and Disease Burden
IMDELLTRA is a first-in-class targeted immunotherapy engineered by Amgen to bind DLL3 on tumor cells and CD3 on T cells, activating T cells to kill DLL3-expressing SCLC cells through a cytolytic synapse. DLL3 is expressed on the surface of SCLC cells in an estimated 85% to 96% of patients but only minimally on healthy tissue, a profile Amgen says makes it an attractive treatment target. IMDELLTRA already holds FDA approval for adults with ES-SCLC whose disease progressed on or after platinum-based chemotherapy, and the DeLLphi-305 results are aimed at extending the IMDELLTRA Imfinzi combination into earlier lines of care.
Tarlatamab, the active compound in IMDELLTRA, is being studied across a wide-ranging DeLLphi program spanning monotherapy and combination regimens, second-line and first-line settings, and both intravenous and subcutaneous dosing formats.
Amgen said it plans to present detailed data from DeLLphi-305 at an upcoming international medical congress and to share the results with regulatory authorities, a step that typically precedes any regulatory filing to expand a drug’s approved indications. For now, the IMDELLTRA Imfinzi combination remains investigational in the first-line maintenance setting, and Amgen cautioned that any scientific information in its announcement relating to new indications is preliminary and not part of the FDA-approved labeling.
Amgen, which helped establish the biotechnology industry more than 45 years ago from its Thousand Oaks headquarters, is one of the 30 companies in the Dow Jones Industrial Average and is also part of the Nasdaq-100 Index. The company said its broader pipeline spans oncology, inflammatory conditions, rare diseases, heart disease, and obesity and obesity-related conditions.
