DeLLphi-301: Tarlatamab phase 2 trial in small cell lung cancer (SCLC)—Efficacy and safety analyzed by presence of brain metastasis.
Anne‐Marie C. Dingemans, Myung‐Ju Ahn, Fiona Blackhall, Martin Reck, Horst-Dieter Hummel, Suresh S. Ramalingam, Melissa L. Johnson, Hiroaki Akamatsu, Juergen Wolf, Jacob Sands, Taofeek K. Owonikoko, Hossein Borghaei, Sujoy Mukherjee, Shuang Huang, Pablo Martínez, Luis Paz‐Ares
Abstract
8015 Background: Brain metastases affect 40%–70% of patients with SCLC. Tarlatamab, a BiTE (bispecific T-cell engager) immunotherapy targeting delta-like ligand 3, demonstrated durable responses and promising survival outcomes in patients with previously treated SCLC (10 mg Q2W) (DeLLphi-301; NCT05060016; Ahn M-J, N Engl J Med 2023). Here, tarlatamab efficacy and safety in patients with baseline brain metastases from DeLLphi-301 are reported. Methods: The DeLLphi-301 study design has been published. Patients with treated, stable, asymptomatic brain metastases were included. Subgroup analyses for efficacy (blinded independent central review [BICR] assessments) and safety by presence or absence of baseline brain metastases were performed. Intracranial activity was assessed. Post enrollment, brain imaging was performed if clinically indicated. Results: As of 27 June 2023, 186 patients had received tarlatamab (ECOG PS: 0–1; median prior lines of therapy: 2; median follow-up: 13.6 months). 29% of patients (54/186) had treated and stable brain metastases at baseline. Most patients (91%) with brain metastases had received prior local radiotherapy; 6% each had received surgery only or both radiotherapy and surgery. Overall systemic objective response rate (ORR; RECIST 1.1) was 45.3% in patients with brain metastases and 32.6% in patients without brain metastases (Table). Any grade immune effector cell associated neurotoxicity syndrome and associated neurological events occurred in 24.1% of patients with brain metastases and in 13.6% of patients without brain metastases; grade ≥ 3 events occurred in the 100 mg group only: 9.4% and 1.8%, respectively, and did not lead to tarlatamab discontinuation in any patient with brain metastases. Analysis of intracranial activity will be presented. Conclusions: Tarlatamab showed promising efficacy and a favorable benefit-risk profile in patients with previously treated SCLC and stable brain metastases. Clinical trial information: NCT05060016 . [Table: see text]