Jacob Sands MD; ESMO 2026: Tarlatamab Bispecific Antibody Maintenance Therapy Prolongs Life for Patients with Extensive Stage Small Cell Lung Cancer

Tarlatamab Bispecific Antibody Maintenance Therapy Prolongs Life for Patients with Extensive Stage Small Cell Lung Cancer

An interview with:

Jacob Sands MD, Associate Chief, Lowe Center for Thoracic Oncology, Dana-Farber Cancer Institute, Assistant Professor of Medicine, Harvard Medical School, Boston, USA

Speaking at:

European Society for Medical Oncology (ESMO) 2026 Annual Congress

MADRID, Spain—Patients with extensive stage small cell lung cancer now have the green-light to add treatment with the bispecific antibody tarlatamab to their maintenance anti-PD-1 immunotherapy after first line chemo-immunotherapy induction.

Results from the phase 3 DeLLphi-305 trial were reported at the 2026 Annual Congress of the European Society for Medical Oncology showing significantly improved overall and progression-free survival.

Peter Goodwin spoke with study author Jacob Sands MD, Associate Chief of the Lowe Center for Thoracic Oncology at the Dana-Farber Cancer Institute, in Boston, USA, and Assistant Professor of Medicine at Harvard Medical School:

AUDIO JOURNAL OF ONCOLOGY; Jacob Sands MD:

Source: ESMO 2026:

LBA3 - Tarlatamab plus durvalumab (durva) vs 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

Abstract

Background

Adding tarlatamab to 1L ES-SCLC therapy showed encouraging efficacy in the phase 1b DeLLphi-303 study (NCT05361395). We report the primary analysis of the randomized phase 3 DeLLphi-305 trial evaluating tarlatamab + durva vs durva as 1LM therapy for ES-SCLC.

Methods

563 patients (pts) with ES-SCLC without progression after 1L durva + EP were randomized (1:1) to receive either tarlatamab + durva (n = 282) or durva (n = 281) until progression or unacceptable toxicity. Tarlatamab was given 1 mg IV cycle 1 day 1 (C1D1); 10 mg IV C1D8, C1D15, then 10 mg IV Q2W; durva was given 1500 mg IV Q4W. The primary endpoint was overall survival (OS) with key secondary endpoint progression-free survival (PFS) per investigator assessment, each measured from time of randomization. Additional secondary endpoints were objective response rate (ORR) and safety.

Results

With median (m) follow-up time of 15.9 and 16.1 months (mo), respectively, tarlatamab + durva significantly improved OS (HR: 0.42; 95% CI 0.32, 0.54; P <0.001; mOS: 21.1 [95% CI, 20.8 to NE] vs 12.7 mo [95% CI, 11.2 to 14.8]). Tarlatamab + durva significantly improved PFS (HR: 0.34; 95% CI 0.28, 0.42; P < 0.001; mPFS: 7.4 vs 1.9 mo). ORR was 26.4% (95% CI 20.9%, 32.5%) for tarlatamab + durva and 4.1% (95% CI 2.0%, 7.4%) for durva (P < 0.001). Grade ≥ 3 TEAEs occurred in 46.8% (tarlatamab + durva) and 40.6% (durva) of pts. Cytokine release syndrome (CRS) and immune-effector cell-associated neurotoxicity syndrome (ICANS) occurred in 49.6% and 1.1% of tarlatamab + durva pts and were mostly low grade (Table). Table: LBA3

Conclusions

Tarlatamab + durva significantly improved OS, PFS, and ORR in 1LM ES-SCLC. The overall incidence of adverse events was comparable between groups. CRS and ICANS events were primarily low grade and no fatal events occurred. These results establish tarlatamab + durva as a new standard of care 1LM therapy for ES-SCLC.

ESMO Comments:

“The survival gains observed with the addition of tarlatamab to durvalumab first-line maintenance are of a magnitude not previously seen in small cell lung cancer (SCLC),” says Dr Stephen Liu from Georgetown Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, US, commenting on the positive results from the phase III DeLLphi-305 trial presented at today’s Presidential Symposium at the ESMO Congress 2026 (Madrid, 23–27 October) (LBA3 ). As reported, the addition of the bispecific T-cell engager immunotherapy, tarlatamab, to maintenance durvalumab significantly improved the primary endpoint of overall survival (OS) compared with durvalumab alone in patients with extensive-stage SCLC (ES-SCLC).