medwireNews: Patients with small-cell lung cancer (SCLC) who have progressed on platinum-based chemotherapy derive a significant overall survival (OS) benefit from treatment with tarlatamab rather than chemotherapy, shows the DeLLphi-304 trial.
The bispecific T-cell engager, which targets both DLL3 and CD3, was well tolerated and significantly improved patient-reported symptoms of dyspnea and cough, reported study author Charles Rudin (Memorial Sloan Kettering Cancer Center, New York, USA) at the 2025 ASCO Annual Meeting in Chicago, Illinois, USA.
He said: “Taking the efficacy and safety data together, I think these data clearly support tarlatamab as a preferable therapy for patients in the second-line setting for small-cell lung cancer.
“Beyond redefining the standard of care for these patients, this study also establishes a new paradigm for the use of bispecific T-cell engager immunotherapies in our patients with lung cancer.”
The phase 3 trial, the results of which were published simultaneously in The New England Journal of Medicine, included 509 patients with SCLC who had received one prior line of platinum-based chemotherapy, either with or without a PD-1- or PD-L1-directed immunotherapy.
The primary endpoint of OS was significantly prolonged among the 254 participants who were randomly allocated to receive tarlatamab relative to their 255 counterparts who instead received single-agent chemotherapy (topotecan, lurbinectedin, or amrubicin), at a median of 13.6 versus 8.3 months, and a hazard ratio (HR) for death of 0.60.
Rudin pointed out that the median follow-up was only 11.2 months in the tarlatamab arm and 11.7 months in the chemotherapy arm, “so it will be interesting to continue to follow these curves out,” but the estimated 1-year OS rates were 53% and 37%, respectively.
Tarlatamab was also associated with better progression-free survival (PFS) than chemotherapy, with a significant HR for progression or death of 0.71.
The median PFS duration was “only modestly improved” with the use of tarlatamab, at 4.2 versus 3.7 months, said the presenter. But he added that although the curves “were almost superimposed” initially, there was “a clear separation at about 6 months that continues to widen over time,” with estimated 1-year PFS rates of 20% and 4%, respectively.
Patients who were treated with tarlatamab reported significant improvements in dyspnea at 18 weeks from baseline on the European Organisation for Research and Treatment of Cancer quality of life questionnaire–core 30 and 13-item lung cancer module, with a least squares mean improvement from baseline of 1.94 points compared with a worsening of 7.20 points for those given chemotherapy.
Similarly, 16.1% of participants in tarlatamab group reported improvements in cough versus 9.0% of those in the chemotherapy group, a significant difference.
The investigator told the audience that “tarlatamab also had a more favorable safety profile relative to chemotherapy,” with treatment-related adverse events (TRAEs) of at least grade 3 occurring in 27% and 62% of patients, respectively.
Fewer patients in the tarlatamab than chemotherapy arm had TRAEs that led to dose interruptions and/or reductions, at respective rates of 19% and 55%, and this was also the case for discontinuations due to TRAEs, at 3% and 6%.
Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome are AEs that “are of concern for patients who are receiving T-cell engagers,” but “events were consistent with tarlatamab’s established safety profile,” and were “generally manageable,” highlighted Rudin.
The discussant – Catherine Meador (Massachusetts General Hospital, Boston, USA) – described the OS benefit as “impressive” and believes that “tarlatamab should now be the standard of care for second-line therapy” in SCLC.
But she stressed the need for further work to optimize administration of tarlatamab, such as monitoring protocols for CRS.
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2025 ASCO Annual Meeting; Chicago, Illinois, USA: 30 May–3 June
N Engl J Med 2025; doi:10.1056/NEJMoa2502099