In the phase II DeLLphi-301 trial—presented at the European Society for Medical Oncology (ESMO) Congress 2023 (Abstract LBA92) and reported by Ahn et al in The New England Journal of Medicine—tarlatamab, a bispecific T-cell engager targeting delta-like ligand 3 and CD3, exhibited activity in patients with previously treated small cell lung cancer.
Study Details
In the open-label trial, 176 patients enrolled at sites in 17 countries between December 2021 and May 2023 were randomly assigned to receive tarlatamab at 10 mg (n = 88) or 100 mg (n = 88) via intravenous infusion. Patients received a step dose of 1 mg of tarlatamab on day 1 of cycle 1, followed by either 10 mg or 100 mg on day 8 and day 15 of cycle 1 and every 2 weeks thereafter in 28-day cycles. After a prespecified interim analysis, 12 additional patients were enrolled in the 10-mg group (n = 100). Patients had received a median of two prior lines of treatment. The primary endpoint was objective response on blinded independent central review.
Responses
Median follow-up was 10.6 months (95% confidence interval [CI] = 9.2–11.3 months) in the 10-mg group and 10.3 months (95% CI = 9.2–11.5 months) in the 100-mg group.
Objective response occurred in 40 of 100 patients (40%, 97.5% CI = 29%–52%) in the 10-mg group, with a complete response in 1 (1%). Median duration of response was not estimable (95% CI = 5.9 months to not estimable). Objective responses were ongoing at data cutoff in 22 responders (55%). The disease control rate was 70%. Median progression-free survival was 4.9 months (95% CI = 2.9–6.7 months). Estimated overall survival rate at 9 months was 68%.
Objective response was observed in 28 of 100 patients (32%, 97.5% CI = 21%–44%) in the 100-mg group, with a complete response in 7 (8%). Median duration of response was not estimable (95% CI = 6.6 months to not estimable). Objective responses were ongoing at data cutoff in 16 responders (57%). The disease control rate was 63%. Median progression-free survival was 3.9 months (95% CI = 2.6–4.4 months). Estimated overall survival rate at 9 months was 66%.
Adverse Events
Grade ≥ 3 adverse events occurred in 59% of patients in the 10-mg group and 64% of those in the 100-mg group. Serious adverse events occurred in 59% vs 71% of patients. Adverse events led to discontinuation of treatment in 7% vs 7% of patients. Any-grade cytokine-release syndrome occurred in 49% (grade ≥ 3 in 0%) vs 61% (grade ≥ 3 in 6%) of patients; immune effector cell–associated neurotoxicity syndrome and associated neurologic events occurred in 7% (grade ≥ 3 in 0%) vs 28% (grade ≥ 3 in 5%). Adverse events led to death in 3% vs 6% of patients, with no deaths considered related to treatment.
The investigators concluded: “Tarlatamab, administered as a 10-mg dose every 2 weeks, showed antitumor activity with durable objective responses and promising survival outcomes in patients with previously treated small cell lung cancer. No new safety signals were identified.”
Luis Paz‑Ares, MD, PhD, of Hospital Universitario 12 de Octubre, Complutense University and Ciberonc, Madrid, is the corresponding author of The New England Journal of Medicine article.
Disclosure: The study was funded by Amgen. For full disclosures of the study authors, visit nejm.org.
