DeLLphi-305: tarlatamab plus durvalumab maintenance more than halved the hazard of death in ES-SCLC

Design

Phase 3, international, open-label randomised trial, interim analysis (DeLLphi-305)

Population

563 patients with ES-SCLC without progression after chemoimmunotherapy

Primary outcome

Overall survival from start of maintenance

Effect

Median OS 21.1 vs 12.7 months; HR 0.42 (95% CI 0.32–0.54); PFS 7.4 vs 1.9 months

DeLLphi-305 was an international, open-label phase 3 trial in 563 patients with extensive-stage small-cell lung cancer who had not progressed after first-line chemoimmunotherapy. They were randomised to maintenance tarlatamab, a DLL3 × CD3 bispecific T-cell engager, plus durvalumab, or durvalumab alone.

At this prespecified interim analysis (median follow-up about 16 months), median overall survival was 21.1 months with the combination against 12.7 months (HR 0.42, 95% CI 0.32 to 0.54). Progression-free survival was 7.4 against 1.9 months (HR 0.34). Grade 3 or worse adverse events were 46.8% against 40.6%. Cytokine release syndrome occurred in nearly half of those on tarlatamab, mostly grade 1 or 2.

An overall survival gain of this size is rare in extensive-stage SCLC. Selection matters: these were patients still responding after induction and fit for maintenance. Tarlatamab requires monitoring for cytokine release syndrome and neurotoxicity, particularly with early doses, which has service implications. Its regulatory status and availability in India should be checked locally.

• Consider tarlatamab-durvalumab maintenance for patients without progression after first-line chemoimmunotherapy, where available.
• Plan monitoring for cytokine release syndrome, which affected nearly half of patients.
• Watch for neurological toxicity, a recognised effect of T-cell engagers.
• Note that benefit applies to patients who reached maintenance, not all diagnosed with ES-SCLC.
• Check regulatory approval and access before discussing this option with patients.

Why it matters

It moves a bispecific T-cell engager into first-line maintenance in a cancer where survival gains have been small.

Don't overread it

This is an interim analysis of an open-label trial in patients selected for no early progression; final results are pending.

The statistics, in plain English

A hazard ratio of 0.42 means the risk of death at any point was about 58% lower. The upper limit of the survival interval for the combination could not yet be estimated, because too few events had occurred.

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