Tarlatamab-Durvalumab Maintenance for Extensive-Stage Small-Cell Lung Cancer

Key numbers

• 95% confidence interval
• 95% CI
• 46.8% of the patients who

Background Patients with extensive-stage small-cell lung cancer have poor outcomes, with a median overall survival of approximately 12 to 13 months. Tarlatamab (a bispecific T-cell engager targeting delta-like ligand 3 [DLL3] and CD3) was previously shown to improve survival as second-line therapy. Whether adding tarlatamab to durvalumab (an anti-programmed death ligand 1 agent) after initial chemoimmunotherapy could significantly improve survival in the context of maintenance therapy after first remission has been unclear. Methods In this phase 3, international, open-label, randomized trial, we compared tarlatamab-durvalumab with durvalumab as first-line maintenance therapy in patients with extensive-stage small-cell lung cancer without progression after initial chemoimmunotherapy. Overall survival and progression-free survival were assessed from randomization at the start of maintenance therapy as the primary and key secondary end points, respectively. Results of the prespecified interim analysis (data-cutoff date, July 7, 2026) are reported here. Results A total of 563 patients were randomly assigned to receive tarlatamab-durvalumab (282 patients) or durvalumab (281 patients). At a median follow-up of 15.9 months in the tarlatamab-durvalumab group and 16.1 months in the durvalumab group, the estimated median overall survival was 21.1 months (95% confidence interval [CI], 20.8 to could not be estimated) with tarlatamab-durvalumab and 12.7 months (95% CI, 11.2 to 14.8) with durvalumab (hazard ratio for death, 0.42; 95% CI, 0.32 to 0.54; P<0.001). The median progression-free survival was 7.4 months (95% CI, 5.6 to 9.1) with tarlatamab-durvalumab and 1.9 months (95% CI, 1.9 to 2.0) with durvalumab (hazard ratio for disease progression or death, 0.34; 95% CI, 0.28 to 0.42; P<0.001). Adverse events of grade 3 or higher occurred in 46.8% of the patients who received tarlatamab-durvalumab and in 40.6% of those who received durvalumab alone. Cytokine release syndrome, mainly of grade 1 or 2, was seen in nearly half the patients receiving tarlatamab-durvalumab. Conclusions Tarlatamab-durvalumab maintenance therapy resulted in significantly longer overall survival and progression-free survival than durvalumab alone among patients with extensive-stage small-cell lung cancer. (Funded by Amgen and AstraZeneca; DeLLphi-305 ClinicalTrials.gov number, NCT06211036.).

Maurice Pérol, Tatsuya Yoshida, Myung-Ju Ahn, Carl M Gay, Martin Schuler, Haifeng Liu, Ahmet Sezer, Ahmet Bilici, Ippokratis Korantzis, Sun Min Lim, Kohei Otsubo, Oscar Juan-Vidal, Yuanbin Chen, Gustavo Schvartsman, Haiyong Wang, Anne-Marie C Dingemans, Jeffrey M Clarke, Aakash Desai, Miguel Marigil, Yuqi Chen, Bazle Abidi, Jessie Wang, Jacob Sands, DeLLphi-305 Investigators

Leverage2 / 5

Reusable within one subfield (a technique, dataset, or protocol a few groups will adopt).

10% of this desk’s rubric

Magnitude3 / 5

Large gain: roughly 2x, or a clear new state of the art on a hard, unsaturated problem.

20% of this desk’s rubric

Evidence5 / 5

Definitive: phase 3 randomized evidence on hard endpoints, multi-lab replication, or community verification at scale.

32% of this desk’s rubric

Novelty3 / 5

A genuinely new approach to an open problem.

8% of this desk’s rubric

Trajectory2 / 5

Some room to improve with obvious engineering.

5% of this desk’s rubric

Stakes3 / 5

Meaningful benefit to many people within a few years.

25% of this desk’s rubric

• Citations0 (reference 20, via openalex, Oct 27, 2026, 06:17 UTC)

• Reviewed by heuristic-v10 on Oct 27, 2026, 06:17 UTC. Paper type: clinical.
• Categories: Journal Article
• BRIEF, No.1 in the Medicine edition of October 27, 2026.