Key Takeaways From DeLLphi-305 at ESMO 2026

Maintenance tarlatamab-dlle (Imdelltra) plus durvalumab significantly improved OS, progression-free survival (PFS), and objective response rate (ORR) vs durvalumab alone in patients with extensive-stage small cell lung cancer (ES-SCLC) who had not progressed after first-line platinum, etoposide, and durvalumab, according to the primary analysis of the phase 3 DeLLphi-305 trial (NCT06211036) presented by Jacob Sands, MD, of Dana-Farber Cancer Institute, at the 2026 ESMO Congress.

The open-label trial randomized 563 patients 1:1 to tarlatamab (10 mg every 2 weeks) plus durvalumab (1500 mg every 4 weeks; n = 282) or durvalumab alone (n = 281) until progression or unacceptable toxicity. OS was the primary end point and PFS the key secondary end point. Brain metastases were present in about 20% of patients and liver metastases in about one-third.

At a July 7, 2026, data cutoff, the interim OS analysis was conducted after 243 events (61% information fraction), with a median follow-up of about 16 months. Median OS was 21.1 months (95% CI, 20.8-not estimable) with the combination vs 12.7 months (95% CI, 11.2-14.8) with durvalumab alone (HR, 0.42; 95% CI, 0.32-0.54; P < .001); 12-month OS rates were 79% vs 53%. Benefit held across subgroups, including patients with brain metastases (HR, 0.49; 95% CI, 0.26-0.93) and liver metastases (HR, 0.41; 95% CI, 0.28-0.61). Median PFS was 7.4 months vs 1.9 months (HR, 0.34; 95% CI, 0.28-0.42; P < .001), and ORR was 26.4% vs 4.1% (P < .001), with a median duration of response of 12.7 vs 5.6 months.

Grade 3 or higher treatment-emergent AEs occurred in 46.8% of patients receiving the combination vs 40.6% with durvalumab alone; treatment-related grade 3 or higher AEs occurred in 20.9% vs 10.8%. Tarlatamab was discontinued for AEs in 5.7% of patients. There were no treatment-related deaths with the combination vs 2 (0.7%) with durvalumab alone. Cytokine release syndrome occurred in 49.6% of patients receiving the combination, with a single grade 3 event, and immune effector cell–associated neurotoxicity syndrome occurred in 1.1%.

Sands concludes that the DeLLphi-305 outcomes “support tarlatamab plus durvalumab as a new standard of care first-line maintenance therapy in extensive-stage small cell lung cancer.”

REFERENCE

Sands J et al. Tarlatamab plus durvalumab (durva) as 1L maintenance (1LM) therapy following durva, platinum, and etoposide (1L durva + EP) in extensive-stage small cell lung cancer (ES-SCLC): primary analysis of the phase 3 DeLLphi-305 trial. Presented at: 2026 ESMO Congress; October 23-27, 2026; Madrid, Spain. Abstract LBA3.