In brief
- In the phase 3 DeLLphi-305 trial, adding tarlatamab to durvalumab maintenance after first-line chemoimmunotherapy lengthened median overall survival to 21.1 months, against 12.7 months with durvalumab alone (hazard ratio for death 0.42; P<0.001).
- Median progression-free survival was 7.4 months with the combination and 1.9 months with durvalumab (hazard ratio 0.34; P<0.001).
- A total of 563 patients with extensive-stage small cell lung cancer whose disease had not progressed on initial chemoimmunotherapy were randomised.
- Grade 3 or higher adverse events occurred in 46.8% of patients given the combination and 40.6% of those given durvalumab alone.
- Cytokine release syndrome, mainly grade 1 or 2, occurred in nearly half of the patients who received tarlatamab.
Study at a glance
- Trial: DeLLphi-305 (NCT06211036), phase 3, international, open-label, randomised
- Population: 563 patients with ES-SCLC without progression after initial chemoimmunotherapy
- Treatment: tarlatamab plus durvalumab (n=282) versus durvalumab alone (n=281) as first-line maintenance
- Primary endpoint: overall survival, measured from randomisation at the start of maintenance
- Overall survival: median 21.1 vs 12.7 months; hazard ratio 0.42
- Progression-free survival: median 7.4 vs 1.9 months; hazard ratio 0.34
- Follow-up: median 15.9 and 16.1 months; interim analysis, data cutoff 7 July 2026
- Safety: grade 3 or higher adverse events in 46.8% vs 40.6%
- Funding: Amgen and AstraZeneca
A maintenance question that earlier trials left open
Outcomes in ES-SCLC remain poor. The authors give a median overall survival of approximately 12 to 13 months for the disease, and the durvalumab arm of this trial landed at 12.7 months, in line with that figure.
Tarlatamab is a bispecific T-cell engager that binds delta-like ligand 3 (DLL3) on tumour cells and CD3 on T cells. It had already been shown to improve survival as second-line therapy. DeLLphi-305 moved the drug earlier, into the maintenance phase after a first remission, and asked whether adding it to the anti-PD-L1 antibody durvalumab would lengthen survival at that point.
An 8.4-month gain in median survival at the interim analysis
Among 563 randomised patients, median overall survival was 21.1 months with tarlatamab plus durvalumab and 12.7 months with durvalumab alone, a hazard ratio for death of 0.42 (P<0.001). Median follow-up was 15.9 months in the combination group and 16.1 months in the control group.
Survival was measured from randomisation at the start of maintenance, not from diagnosis. Patients therefore entered the trial having already completed chemoimmunotherapy without progression, and the medians apply to that selected population. The upper confidence limit for median overall survival in the combination arm could not yet be estimated, which reflects the immaturity of the interim data.
Progression-free survival nearly four times longer
The key secondary endpoint moved in the same direction. Median progression-free survival was 7.4 months with the combination and 1.9 months with durvalumab, a hazard ratio for progression or death of 0.34 (P<0.001).
The 1.9-month median in the control arm shows how quickly disease progressed on durvalumab alone once induction had ended. The trial was open-label, so investigators and patients knew the assigned treatment, a point that matters more for progression-free survival than for overall survival.
More severe adverse events and frequent cytokine release syndrome
Adverse events of grade 3 or higher occurred in 46.8% of patients who received tarlatamab plus durvalumab and in 40.6% of those who received durvalumab alone. Cytokine release syndrome was seen in nearly half of the patients in the combination arm, mainly at grade 1 or 2.
The abstract does not break the higher-grade events down by type, and it does not report rates of neurological toxicity or treatment discontinuation. Cytokine release syndrome is a known effect of T-cell engagers, and its frequency here bears on how and where maintenance dosing could be delivered.
Interim results from a trial funded by both drug makers
The authors state their conclusion directly.
“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.”Pérol et al., New England Journal of Medicine (2026)
These are results of a prespecified interim analysis with a data cutoff of 7 July 2026, and longer follow-up will show whether the survival difference holds. The trial was funded by Amgen, which makes tarlatamab, and AstraZeneca, which makes durvalumab.
Sources
- New England Journal of Medicine. Tarlatamab–Durvalumab Maintenance for Extensive-Stage Small-Cell Lung Cancer (2026-10-24). doi.org
Featuring Lung Summit faculty
This study was co-authored by Lung Summit faculty Jacob Sands, Maurice Pérol and Anne-Marie Dingemans.
This article was produced independently by the Lung Summit editorial team, without industry funding or input.
