Faculty Collaboration Database

Tarlatamab in Small-Cell Lung Cancer after Platinum-Based Chemotherapy. N Engl J Med 2025 Jul 24;393(4):349-361

Date

06/02/2025

Pubmed ID

40454646

DOI

10.1056/NEJMoa2502099

Scopus ID

2-s2.0-105012375634 (requires institutional sign-in at Scopus site)   173 Citations

Abstract

BACKGROUND: Tarlatamab, a bispecific delta-like ligand 3-directed T-cell engager immunotherapy, received accelerated approval for the treatment of patients with previously treated small-cell lung cancer. Whether tarlatamab is more effective than chemotherapy in the treatment of patients whose small-cell lung cancer has progressed during or after initial platinum-based chemotherapy is not known.

METHODS: We conducted a multinational, phase 3, open-label trial to compare tarlatamab with chemotherapy as second-line treatment in patients with small-cell lung cancer whose disease had progressed during or after platinum-based chemotherapy. Patients were randomly assigned to receive tarlatamab or chemotherapy (topotecan, lurbinectedin, or amrubicin). The primary end point was overall survival. Key secondary end points were investigator-assessed progression-free survival and patient-reported outcomes. Results of the prespecified interim analysis (data-cutoff date, January 29, 2025) are reported.

RESULTS: A total of 509 patients were randomly assigned to receive tarlatamab (254 patients) or chemotherapy (255 patients). Treatment with tarlatamab resulted in significantly longer overall survival than chemotherapy (median, 13.6 months [95% confidence interval {CI}, 11.1 to not reached] vs. 8.3 months [95% CI, 7.0 to 10.2]; stratified hazard ratio for death, 0.60; 95% CI, 0.47 to 0.77; P<0.001). Tarlatamab treatment also had a significant benefit with respect to progression-free survival and cancer-related dyspnea and cough as compared with chemotherapy. The incidence of adverse events of grade 3 or higher was lower with tarlatamab than with chemotherapy (54% vs. 80%), as was the incidence of adverse events resulting in treatment discontinuation (5% vs. 12%).

CONCLUSIONS: Treatment with tarlatamab led to longer overall survival than chemotherapy among patients with small-cell lung cancer whose disease had progressed during or after platinum-based chemotherapy. (Funded by Amgen; DeLLphi-304 ClinicalTrials.gov number, NCT05740566.).

Author List

Mountzios G, Sun L, Cho BC, Demirci U, Baka S, Gümüş M, Lugini A, Zhu B, Yu Y, Korantzis I, Han JY, Ciuleanu TE, Ahn MJ, Rocha P, Mazières J, Lau SCM, Schuler M, Blackhall F, Yoshida T, Owonikoko TK, Paz-Ares L, Jiang T, Hamidi A, Gauto D, Recondo G, Rudin CM, DeLLphi-304 Investigators

Author

Hui-Zi Chen PhD, MD Assistant Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adult
Aged
Aged, 80 and over
Anthracyclines
Antibodies, Bispecific
Antineoplastic Agents, Immunological
Antineoplastic Combined Chemotherapy Protocols
Carbolines
Cough
Disease Progression
Dyspnea
Female
Heterocyclic Compounds, 4 or More Rings
Humans
Lung Neoplasms
Male
Middle Aged
Severity of Illness Index
Small Cell Lung Carcinoma
Topotecan
Treatment Outcome
Young Adult