Durvalumab Combo Improves Survival in First-Line Extensive-Stage SCLC

Durvalumab (Imfinzi) plus tarlatamab-dlle (Imdelltra) demonstrated a statistically significant and clinically meaningful improvement in overall survival (OS) vs durvalumab alone as first-line maintenance treatment for patients with extensive-stage small cell lung cancer (ES-SCLC), according to a planned interim analysis of the phase 3 DeLLphi-305 trial (NCT06211036) announced by AstraZeneca.¹

The trial enrolled patients who had not progressed following standard induction treatment with durvalumab plus platinum-based chemotherapy and etoposide. Developers stated that this is the first immunotherapy combined with a bispecific T-cell engager to show a survival benefit in this setting.

What did the DeLLphi-305 trial show?

The combination met its primary end point, demonstrating a statistically significant and highly clinically meaningful improvement in OS vs durvalumab alone. Durvalumab plus tarlatamab also produced statistically significant and clinically meaningful improvements in the secondary end points of progression-free survival (PFS) and objective response rate (ORR).

The safety and tolerability profile of the combination was consistent with the known profiles of the individual agents, with no new safety signals identified. Detailed results will be presented at an upcoming medical meeting and shared with global regulatory authorities.

“Given the aggressive nature of [SCLC], 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 the news release.¹ “In my career treating [patients] with [ES-SCLC], these are among the most compelling survival results I have seen, indicating the potential to reshape the natural history of [SCLC]. DeLLphi-305 represents an unprecedented milestone and suggests we may be entering a new era where meaningfully longer survival is possible for more patients.”

What is the DeLLphi-305 trial design?

DeLLphi-305 is a global, randomized, open-label phase 3 trial evaluating durvalumab plus tarlatamab vs durvalumab alone as first-line maintenance treatment in patients with ES-SCLC who had not progressed following induction with durvalumab plus platinum-based chemotherapy and etoposide. A total of 563 patients who completed induction were randomly assigned 1:1 to receive either the combination or durvalumab alone until disease progression or unacceptable toxicity. The trial included patients with both treated and untreated asymptomatic brain metastases at baseline. Following tarlatamab infusions on cycle 1, day 1 and cycle 1, day 8, patients were monitored in a health care setting for 1 to 2 hours or 6 to 8 hours in certain regions, including Europe.

The primary end point was OS. PFS was a key secondary end point. Additional secondary end points included ORR, disease control rate, duration of response, and time to progression.² Patients 18 years and older with 3 to 4 prior cycles of platinum-etoposide chemotherapy with concurrent durvalumab as frontline treatment for ES-SCLC, an ECOG performance status of 0 or 1, and a minimum life expectancy of more than 12 weeks were eligible for enrollment on the trial.

What are durvalumab and tarlatamab?

Durvalumab is a human monoclonal antibody that binds to PD-L1 and blocks its interaction with PD-1 and CD80, countering tumor immune evasion. Tarlatamab is a first-in-class bispecific T-cell engager that binds both DLL3 on tumor cells and CD3 on T cells, activating T cells to kill SCLC cells that express DLL3, which is seen on the surface of SCLC cells in approximately 85% to 96% of patients with SCLC but is minimally expressed on healthy cells.

What is the regulatory context for these agents in SCLC?

Previously, tarlatamab earned traditional FDA approval for patients with relapsed ES-SCLC whose disease progressed on or after platinum-based chemotherapy in November 2025 based on data from the phase 3 DeLLphi-304 trial (NCT05740566).³ Tarlatamab subsequently received European Commission approval as a treatment for those with ES-SCLC in June 2026.⁴

Durvalumab is approved in the US, EU, Japan, China, and other countries as a standard-of-care treatment for ES-SCLC and limited-stage SCLC, based on the phase 3 CASPIAN (NCT03043872) and ADRIATIC trials (NCT03703297), respectively. DeLLphi-305 extends the evaluation of tarlatamab into the first-line maintenance setting in combination with durvalumab.

References

1. Imfinzi plus Imdelltra demonstrated a statistically significant and highly clinically meaningful improvement in overall survival and progression-free survival in 1st-line extensive-stage small cell lung cancer. News release. AstraZeneca. September 8, 2026. Accessed September 9, 2026. https://tinyurl.com/fy6erm5p
2. Study comparing tarlatamab and durvalumab versus durvalumab alone in first-line extensive-stage small-cell lung cancer (ES-SCLC) following platinum, etoposide and durvalumab (DeLLphi-305). ClinicalTrials.gov. Updated December 17, 2025. Accessed September 9, 2026. https://tinyurl.com/bjpweytr
3. FDA grants traditional approval to tarlatamab-dlle for extensive stage small cell lung cancer. News release. FDA. November 19, 2025. Accessed September 9, 2026. https://tinyurl.com/yc7b96fw
4. European Commission approves Amgen’s Imdylltra® for the treatment of extensive-stage small cell lung cancer. News release. Amgen. June 1, 2026. Accessed September 9, 2026. https://tinyurl.com/mtndpuma