Tarlatamab Plus Durvalumab Significantly Improves Overall Survival in Patients With Extensive-Stage Small Cell Lung Cancer
Clinical Summary:
- Design/Population: The phase 3 DeLLphi-305 trial evaluated tarlatamab plus durvalumab versus durvalumab alone as first-line maintenance therapy in patients with extensive-stage small cell lung cancer (ES-SCLC) who had not experienced disease progression following induction treatment with durvalumab, platinum-based chemotherapy, and etoposide.
- Key Outcomes: Tarlatamab plus durvalumab significantly improved overall survival, progression-free survival, and objective response, reducing the risk of death by 58% and the risk of disease progression or death by 66% compared with durvalumab alone. Cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome were predominantly low grade.
- Clinical Relevance: These findings support the addition of tarlatamab to durvalumab as a potential new first-line maintenance strategy for ES-SCLC, demonstrating substantial survival benefits following induction chemoimmunotherapy.
Results from the phase 3 DeLLphi-305 trial demonstrated that tarlatamab plus durvalumab significantly improved overall survival (OS), progression-free survival (PFS), and objective response compared with durvalumab alone as first-line maintenance therapy for patients with extensive-stage small cell lung cancer (ES-SCLC), supporting the combination as a potential new treatment standard.
These findings were presented by Jacob Sands, MD, Dana-Farber Cancer Institute, Boston, Massachusetts, during a Presidential Symposium at the European Society for Medical Oncology (ESMO) Congress.
In this trial, 563 patients with ES-SCLC who had not experienced disease progression following first-line durvalumab plus platinum-based chemotherapy and etoposide were randomized 1:1 to receive either tarlatamab plus durvalumab (n = 282) or durvalumab alone (n = 281) until disease progression or unacceptable toxicity.
Patients in the combination arm received 1 mg of tarlatamab intravenously on cycle 1, day 1, followed by 10 mg on days 8 and 15 and every 2 weeks thereafter. Durvalumab was administered at 1500 mg intravenously every 4 weeks in both treatment arms.
The primary end point was OS. Key secondary end points included investigator-assessed PFS, objective response rate (ORR), and safety. Survival outcomes were measured from randomization.
At analysis, median OS was 21.1 months in the tarlatamab plus durvalumab arm and 12.7 months in the durvalumab monotherapy arm. The addition of tarlatamab reduced the risk of death by 58% (hazard ratio [HR], 0.42; 95% confidence interval [CI], 0.32 to 0.54; P < .001). The 12-month OS rates were 79.4% and 53.3%, respectively.
Median PFS was 7.4 months in the tarlatamab plus durvalumab arm and 1.9 months in the durvalumab monotherapy arm, reducing the risk of disease progression or death by 66% (HR, 0.34; 95% CI, 0.28 to 0.42; P < .001). The ORR was 26.4% and 4.1%, respectively (P < .001).
Overall safety findings were consistent with the known profiles of the individual agents. Grade ≥3 treatment-emergent adverse events were reported in 46.8% of patients receiving tarlatamab plus durvalumab and 40.6% of patients receiving durvalumab monotherapy. Adverse events of any grade were reported in 99.6% and 92.8% of patients, respectively.
Cytokine release syndrome (CRS) occurred in 49.6% of patients receiving tarlatamab plus durvalumab and 1.4% of patients receiving durvalumab monotherapy. Grade ≥3 CRS occurred in 0.4% of patients in the combination arm, with no grade ≥3 events reported in the control arm.
Immune effector cell-associated neurotoxicity syndrome (ICANS) occurred in 1.1% of patients receiving tarlatamab plus durvalumab and was not reported among patients receiving durvalumab monotherapy. No grade ≥3 ICANS events were reported.
No fatal CRS or ICANS events occurred in either treatment arm. Although CRS was more frequent with the addition of tarlatamab, events were predominantly low grade.
“These results establish tarlatamab plus durvalumab as a new standard of care first-line maintenance therapy for ES-SCLC,” concluded Dr Sands.
Source:
Sands J, et al. Tarlatamab plus durvalumab (durva) vs durva as 1L maintenance (1LM) therapy following durva, platinum, and etoposide (1L durva + EP) in extensive-stage small cell lung cancer (ES-SCLC): Primary analysis of the phase 3 DeLLphi-305 trial. Presented at ESMO Congress. October 23-27, 2026; Madrid, Spain. LBA3.
