As reported on PharmaBiz, a combination of Imfinzi (durvalumab) and Imdelltra (tarlatamab) has delivered significant improvements in survival outcomes for patients with extensive-stage small cell lung cancer (ES-SCLC), according to interim findings from the phase III DeLLphi-305 trial.
The study evaluated the addition of tarlatamab to maintenance treatment with durvalumab in patients whose disease had not progressed after first-line induction therapy consisting of durvalumab plus platinum-based chemotherapy and etoposide. Investigators reported that the combination achieved a statistically significant and clinically meaningful improvement in overall survival (OS) compared with durvalumab maintenance alone.
The regimen also met key secondary endpoints, demonstrating notable gains in progression-free survival (PFS) and objective response rate (ORR).
Addressing a Major Unmet Need
Small cell lung cancer remains one of the most aggressive forms of lung cancer, characterized by rapid growth, early metastasis, and frequent relapse. Approximately two-thirds of patients are diagnosed with extensive-stage disease, where cancer has already spread beyond the lung. Although the introduction of immune checkpoint inhibitors such as durvalumab has improved outcomes, many patients still experience disease progression within a relatively short period, and median survival remains around one year.
Against this backdrop, the DeLLphi-305 results suggest that intensifying maintenance therapy may offer a meaningful opportunity to extend survival earlier in the treatment journey, when patients are most likely to benefit.
Expert Perspectives
Susan Galbraith, Executive Vice President of Oncology Hematology R&D at AstraZeneca, described the findings as a potentially transformative advance for patients with extensive-stage disease. She noted that the results further reinforce durvalumab’s role as a key immunotherapy backbone in small cell lung cancer treatment.
Commenting on the data, Jacob Sands, MD, of the Dana-Farber Cancer Institute, emphasized the importance of improving outcomes in the first-line setting, as many patients with ES-SCLC deteriorate rapidly and never reach subsequent lines of therapy. He characterized the survival benefit observed in DeLLphi-305 as among the most impressive reported in this patient population and suggested the results could alter expectations for long-term outcomes.
Safety Profile Remains Consistent
Investigators reported that the safety profile of the durvalumab-tarlatamab combination aligned with the known adverse-event profiles of the individual agents. No new safety concerns were identified during the analysis.
Detailed efficacy and safety findings are expected to be presented at an upcoming scientific meeting and submitted to regulatory agencies worldwide.
About DeLLphi-305
The global, randomized, open-label phase III study enrolled 563 patients with ES-SCLC who had completed induction treatment with durvalumab, platinum chemotherapy, and etoposide without disease progression. Participants were randomized to receive either durvalumab plus tarlatamab or durvalumab alone as maintenance therapy until disease progression or unacceptable toxicity occurred.
The trial’s primary endpoint is overall survival, with progression-free survival serving as a key secondary endpoint.
How Tarlatamab Works
Tarlatamab is a first-in-class bispecific T-cell engager designed to target DLL3, a protein expressed on the surface of the vast majority of small cell lung cancer cells but largely absent from healthy tissue. The therapy simultaneously binds DLL3 on tumor cells and CD3 on T cells, activating the immune system to recognize and destroy DLL3-expressing cancer cells.
Durvalumab’s Established Role in SCLC
Durvalumab is already approved in multiple regions, including the United States, Europe, Japan, and China, for the treatment of both extensive-stage and limited-stage small cell lung cancer. Its approvals are supported by the phase III CASPIAN and ADRIATIC studies, which helped establish immunotherapy-based approaches as standards of care in this disease.
With positive interim results from DeLLphi-305, the addition of tarlatamab to durvalumab maintenance therapy may represent an important next step in improving outcomes for patients with extensive-stage small cell lung cancer, a disease that continues to carry one of the poorest prognoses in oncology.
