November 3rd, 2026
Summary by Catlin Nalley
Patients with previously treated small cell lung cancer (SCLC) who received tarlatamab continued to experience improved survival compared with those treated with chemotherapy, according to extended follow-up findings from the phase III DeLLphi-304 trial presented during the 2026 European Society for Medical Oncology (ESMO) Congress in Madrid (Abstract 3808O). The findings were simultaneously published in Annals of Oncology.
“With extended follow-up, tarlatamab demonstrated a durable survival benefit with a manageable safety profile versus chemotherapy, with no new safety signals, reinforcing its role as the standard of care treatment in pts with SCLC after first-line platinum-based chemotherapy, including those with high-risk disease,” noted lead study author Charles M. Rudin, MD, PhD, at Memorial Sloan Kettering Cancer Center, New York, and colleagues.
Study Overview
DeLLphi-304 was a randomized phase III trial comparing tarlatamab with investigator-selected chemotherapy in patients with SCLC previously treated with first-line platinum-based chemotherapy. A total of 509 patients were included in the reported efficacy analysis, with 254 assigned to tarlatamab and 255 to chemotherapy.
The chemotherapy options were topotecan, lurbinectedin, or amrubicin, the latter available as an option in Japan. Patients with asymptomatic brain metastases, whether previously treated or untreated, were eligible to participate.
The primary endpoint was overall survival and secondary endpoints included progression-free survival (PFS), disease control (DC), duration of response (DOR), and safety.
In the initial analysis, conducted at the first planned interim analysis, median OS was 13.6 months with tarlatamab compared with 8.3 months with chemotherapy, after median follow-up of 11.2 and 11.7 months, respectively.
The extended analysis had a median follow-up of 23 months, providing additional information on survival outcomes beyond the initial analysis. The investigators also examined outcomes in higher-risk subgroups, including patients with platinum-resistant disease and those with brain metastases at baseline.
Extended Survival & Disease Control Outcomes
The OS benefit with tarlatamab persisted with longer follow-up. Median OS was 13.6 months compared with 8.4 months with chemotherapy (HR: 0.62; 95% CI: 0.51-0.76).
Landmark survival rates also favored tarlatamab. At 12 months, the OS rate was 56% with tarlatamab versus 39% with chemotherapy. At 18 months, the corresponding rates were 42% and 24%.
The benefit was maintained in prespecified high-risk subgroups. Among patients with platinum-resistant disease, defined as a chemotherapy-free interval of less than 90 days, the HR for death was 0.65 (95% CI: 0.48–0.86). Among patients with baseline brain metastases, the HR was 0.52 (95% CI: 0.38–0.70).
Investigators also observed improved PFS with tarlatamab. Median PFS was 4.2 months among patients treated with tarlatamab versus 3.2 months in the chemotherapy group (HR: 0.69; 95% CI, 0.57–0.84). At 12 months, the PFS rate was 21% and 6%, respectively.
Median DOR was 7.1 months with tarlatamab versus 5.5 months with chemotherapy. Among responders, 42% in the tarlatamab arm maintained their response at 12 months, compared with 10% in the chemotherapy group.
The overall disease control rate was 68% with tarlatamab and 64% with chemotherapy. However, sustained disease control lasting at least 52 weeks was observed in 24% of patients receiving tarlatamab versus 4% receiving chemotherapy.
Safety & Long-Term Tolerability
Tarlatamab continued to demonstrate a favorable safety profile compared with chemotherapy. Grade 3 or higher treatment-related adverse events occurred in 28% of patients receiving tarlatamab versus 63% of those receiving chemotherapy. Treatment discontinuation due to treatment-related adverse events was also less frequent with tarlatamab (3% versus 7%).
Rudin reported that median treatment exposure was longer with tarlatamab than with chemotherapy, at approximately 18 months versus 10 months, respectively. Despite the longer exposure, no new safety signals emerged, and treatment-related toxicities generally decreased over time.
Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), adverse events of particular interest with T-cell-engaging therapies, occurred predominantly early in treatment. These events were generally low grade, with CRS becoming uncommon after the initial treatment cycles and few later ICANS events reported.
Chemotherapy-associated toxicities included hematologic and gastrointestinal adverse events and fatigue. The investigators noted that, unlike the cumulative toxicity often associated with chemotherapy, tarlatamab-related adverse events tended to occur early and diminish with continued treatment.
Clinical Significance
The extended DeLLphi-304 results demonstrate that the survival advantage previously observed with tarlatamab continued at a median follow-up of 23 months. Improvements in OS and PFS were accompanied by more durable responses and sustained disease control, while rates of high-grade treatment-related adverse events and treatment discontinuation remained lower than with chemotherapy.
“Now, at about a 2-year benchmark, the 23-month long-term follow-up of the phase III DeLLphi-304 trial continues to demonstrate durable clinical benefit with tarlatamab versus chemotherapy,” noted Rudin, while emphasizing the persistence of survival benefit and the durability of disease control as well as a safety profile that “continues to reassure us that this is safe and preferable, frankly, to chemotherapy.”
Concluding his ESMO presentation, Rudin said, “Extended follow-up of what we’ve seen here, and also in the DeLLphi-305 trial, really reinforces tarlatamab as the standard-of-care choice after first-line platinum-based chemotherapy for patients with extensive-stage small cell lung cancer."