First survival boost beyond immunotherapy alone in extensive-stage small cell lung cancer

Clinical takeaway: Adding tarlatamab to durvalumab may eventually offer a more effective maintenance option for patients whose cancer has not progressed after initial durvalumab, platinum chemotherapy, and etoposide. The combination is not yet approved for this use, and full efficacy and safety data are needed before practice changes.

Extensive-stage small cell lung cancer often responds initially to treatment but returns quickly. Some patients deteriorate so rapidly after progression that they never receive second-line therapy, making more effective treatment before relapse an important clinical goal.

In the phase 3 DeLLphi-305 trial, 563 patients whose cancer had not progressed after initial treatment with durvalumab, platinum chemotherapy, and etoposide were randomly assigned to receive maintenance therapy with durvalumab plus tarlatamab or durvalumab alone.

At a planned interim analysis, adding tarlatamab significantly improved overall survival, the study’s primary endpoint. The combination also delayed disease progression and increased tumor response rate. However, median survival, hazard ratios, and detailed safety results have not yet been released, so the clinical significance of the improvements cannot yet be fully evaluated.

Tarlatamab is a targeted immunotherapy that connects immune T cells to DLL3, a protein found on most small cell lung cancer cells, helping the immune system attack the cancer. It is already FDA-approved on its own for adults whose extensive-stage disease has progressed during or after platinum-based chemotherapy. These findings suggest that using it earlier—before the cancer progresses—could help more patients benefit.

The study included patients with treated or untreated brain metastases that were not causing symptoms, a common clinical concern in this disease. No new safety signals were reported. Still, tarlatamab can cause serious cytokine release syndrome and neurologic toxicity, requiring step-up dosing and monitoring.

Detailed findings will be presented at an upcoming medical meeting and shared with regulatory authorities.

“These are among the most compelling survival results I have seen, indicating the potential to reshape the natural history of small cell lung cancer,” said Jacob Sands, MD, of Dana-Farber Cancer Institute.

Source: AstraZeneca. (2026 Sep 8). Imfinzi plus Imdelltra demonstrated a statistically significant and highly clinically meaningful improvement in overall survival and progression-free survival in 1st-line extensive-stage small cell lung cancer