Tarlatamab shows promise for previously treated SCLC

medwireNews: The bispecific T-cell engager tarlatamab has demonstrated durable antitumor activity and acceptable safety in previously treated patients with extensive-stage small-cell lung cancer (SCLC) in the DeLLphi-301 trial. The findings were presented at the ESMO Congress 2023 in Madrid, Spain, by Luis Paz-Ares (Hospital Universitario 12 de Octubre, Madrid) and published simultaneously in The New England Journal of Medicine. The researchers explain that tarlatamab is an immunotherapy that targets both delta-like ligand 3 (DLL3) and CD3 and has shown “encouraging antitumor activity” in a phase 1 dose-exploration study in pretreated SCLC patients. The current phase 2 trial recruited 222 individuals who had received two or more lines of therapy; of these, 176 received intravenous tarlatamab at a dose of either 10 mg or 100 mg in the dose-comparison part 1 of the study, while 12 received the selected 10 mg dose in part 2 and 34 in part 3 (a substudy evaluating the safety when inpatient monitoring in the first cycle was reduced from 48 to 24 hours). In all three parts, tarlatamab was initially given at a dose of 1 mg on day 1 of the first cycle, followed by the target dose on days 8 and 15, after which the drug was given every 2 weeks. Among the 188 participants evaluable for efficacy, the objective response rate as per blinded independent central review was 40% among the 100 who received tarlatamab 10 mg and 32% among the 88 given the 100 mg dose. Participants were followed up for a median of 10.6 and 10.3 months, respectively. The objective response rate “far exceeded the historical control benchmark of 15% for the primary end point,” point out Paz-Ares and colleagues. The median duration of response was not reached in either the 10 or 100 mg dose group. But among the 68 responders, 59% had a response that lasted at least 6 months and 29% had a response that lasted at least 9 months. Progression-free survival was a median of 4.9 months in the 10 mg group and 3.9 months in the 100 mg group, while the respective durations of median overall survival were 14.3 months and unreached. The investigators comment: “Results from this trial can be viewed favorably in the context of real-world studies of drugs for third-line use and beyond, in which objective responses occurred in 14 to 21% of the patients, median response durations were less than 3 months, and median overall survival durations were less than 6 months.” Safety was assessed in all 220 participants, and treatment-related adverse events (TRAEs) of at least grade 3 were observed in 26% of patients who received the 10 mg dose and 33% of those given the 100 mg dose. A total of 13% of patients in the 10 mg group required a dose interruption or reduction or both due to TRAEs, as did 29% of those in the 100 mg group, while 3% in each group discontinued treatment as a result. One death in a patient who received tarlatamab 10 mg was deemed related to the study drug by the investigator. Paz-Ares and associates also report on certain AEs of interest, namely cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome (ICANS) in light of the mechanism of action of tarlatamab. The former occurred in 51% of the 10 mg group and 61% of the 100 mg group, but events were “predominantly grade 1 or 2 in severity” and “generally managed with supportive care, such as acetaminophen, intravenous hydration, and glucocorticoids, alone or in combination,” say the researchers. ICANS and associated neurologic events were experienced by 8% of patients given the 10 mg dose and 28% of those who received the 100 mg dose, with grade 3 or worse events occurring in none and 5% of patients, respectively. “Tarlatamab represents a new immunotherapeutic approach for small-cell lung cancer, a tumor type that is characterized by an immunosuppressive microenvironment,” conclude Paz-Ares et al. They acknowledge the lack of a standard care comparator therapy as a limitation of the trial but note that the ongoing phase 3 DeLLphi-304 study addresses this concern. medwireNews is an independent medical news service provided by Springer Healthcare Ltd. © 2023 Springer Healthcare Ltd, part of the Springer Nature Group ESMO Congress 2023; Madrid, Spain: 20–24 October N Engl J Med 2023; doi:10.1056/NEJMoa2307980

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Tarlatamab shows promise for previously treated SCLC

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