Adding tarlatamab to durvalumab maintenance therapy significantly improved progression-free survival and overall survival in patients with extensive-stage small cell lung cancer compared with durvalumab alone, according to results from the phase 3 DeLLphi-305 trial presented at the European Society for Medical Oncology (ESMO) Congress 2026 and published in the New England Journal of Medicine.
The trial demonstrated a 58% reduction in the risk of death and a 66% reduction in the risk of disease progression or death. At a median follow-up of about 16 months, the median overall survival reached 21.1 months in the tarlatamab plus durvalumab group compared with 12.7 months for durvalumab alone. Median progression-free survival was 7.4 months versus 1.9 months.
Study Enrolls 563 Adults with Lung Cancer
The open-label study enrolled 563 adults with extensive-stage small cell lung cancer who had undergone first-line platinum-etoposide chemotherapy with durvalumab induction therapy and experienced no disease progression. Participants were randomized to receive either 10 mg of tarlatamab once every two weeks with 1,500 mg of durvalumab every four weeks, or durvalumab alone.
The study population had a median age of 65 years and was predominantly male (71%) and White (61%). Most participants had a history of smoking (90%) and received carboplatin (84%), while 16% received cisplatin. Approximately 85% achieved a partial response to initial therapy, 33% had current or prior liver metastases, and 20% had current or prior brain metastases.
Investigators Observe Cytokine Release Syndrome in Patients
Investigators observed cytokine release syndrome in 50% of patients receiving the combination therapy, with only one case reaching grade 3 severity. Both progression-free and overall survival benefits remained consistent across prespecified subgroups, including patients with or without brain or liver metastases.
Phase 1b data from the previous year showed a median overall survival of 25.3 months, which was updated at ESMO to 37.9 months, providing the context for evaluating the DeLLphi-305 maintenance regimen.
