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Tarlatamab for Previously Treated Small-Cell Lung Cancer
Tarlatamab is a bispecific T-cell engager that targets delta-like ligand 3 and CD3. In the industry-funded, phase 2 DeLLphi-301 study, researchers evaluated the activity and safety of tarlatamab in 220 patients with advanced small-cell lung cancer (SCLC) previously treated with two or more lines of therapy. In the open-label trial, patients received either 10 mg or 100 mg of tarlatamab every 2 weeks.
At a median follow-up of approximately 10 months, the objective response rate – the primary endpoint — among the 188 evaluable patients was 40% in the 10-mg group and 32% in the 100-mg group. Among 68 patients with an objective response, the duration of response was ≥6 months in 59%. The estimated overall survival rate at 9 months was 68% in the 10-mg group and 66% in the 100-mg group.
The most common treatment-emergent adverse event was cytokine release syndrome (CRS), which occurred in 51% of the 10-mg group and 61% of the 100-mg group. Most cases occurred during the first treatment cycle and were grade 1 or 2 severity. Grade 3 CRS occurred in 1% of the 10-mg group and 6% of the 100-mg group. Immune effector cell-associated neurotoxicity syndrome and associated neurologic events occurred in 8% of the 10-mg group and 28% of the 100-mg group and were grade ≥3 in 0% and 5%, respectively. No deaths were related to treatment.
The authors concluded that tarlatamab at a dose of 10 mg every 2 weeks was appropriate to move forward for additional study. Second-line treatment options for SCLC thus far have been characterized by low response rates and short durations of response. Tarlatamab represents a new treatment approach that is targeted at overcoming the immunosuppressive microenvironment in SCLC. Further study is needed to assess the long-term durability of response, long-term survival benefits, and feasibility of treatment in broader populations.
Ahn M-J et al.
Title: Tarlatamab for patients with previously treated small-cell lung cancer.
Source: N Engl J Med 2023 Oct 20; [e-pub]. (Abstract/FREE Full Text)