Tarlatamab Plus Durvalumab Improves Survival as First-Line Maintenance Therapy in Extensive-Stage Small Cell Lung Cancer

Clinical Summary:

• Design/Population: This open-label, phase 3 trial evaluated tarlatamab plus durvalumab as first-line maintenance therapy in patients with extensive-stage small cell lung cancer whose disease had not progressed following initial durvalumab, platinum-based chemotherapy, and etoposide.
• Key Outcomes: Tarlatamab plus durvalumab significantly improved overall survival, meeting the primary end point at a prespecified interim analysis. The combination also significantly improved progression-free survival and objective response, with no new or unexpected safety signals.
• Clinical Relevance: These findings support moving DLL3-directed T-cell engagement into the first-line maintenance setting and position tarlatamab plus durvalumab as a potentially practice-changing strategy for patients with extensive-stage small cell lung cancer who have not progressed after initial chemoimmunotherapy. 

Topline results from the phase 3 DeLLphi-305 study demonstrated that tarlatamab plus durvalumab significantly improved overall survival (OS) compared with durvalumab alone as first-line maintenance treatment for patients with extensive-stage small cell lung cancer (ES-SCLC) whose disease had not progressed following initial chemoimmunotherapy. 

In this open-label trial, 563 patients were randomized 1:1 to receive either tarlatamab plus durvalumab or durvalumab alone until disease progression or unacceptable toxicity. Patients with treated and untreated asymptomatic brain metastases were eligible for enrollment. 

The primary end point was OS. Key secondary end points included progression-free survival (PFS), objective response rate (ORR), and safety. 

At a prespecified interim analysis, tarlatamab plus durvalumab produced a statistically significant and clinically meaningful improvement in OS compared with durvalumab alone, meeting the study’s primary end point. The combination also demonstrated statistically significant and clinically meaningful improvements in PFS and ORR. 

Detailed efficacy results, including the magnitude of the OS and PFS benefits, were not reported in the topline announcement and are planned for presentation at an upcoming international medical congress.

The overall safety profile of tarlatamab plus durvalumab was consistent with the known established safety profiles of the individual agents, with no new or unexpected safety signals identified in DeLLphi-305. 

The study incorporated luded healthcare-setting monitoring following tarlatamab administration on cycle 1, days 1 and 8. Patients were monitored for 1 to 2 hours following infusion, with longer monitoring periods used in certain regions. 

Tarlatamab is a DLL3-directed bispecific T-cell engager designed to simultaneously bind DLL3 on SCLC cells and CD3 on T cells, activating T cells to induce tumor cell lysis. The agent is currently FDA approved for adults with ES-SCLC whose disease has progressed on or after platinum-based chemotherapy.

DeLLphi-305 therefore evaluates tarlatamab earlier in the treatment course, before disease progression following first-line chemoimmunotherapy. According to the reported findings, this is the first phase 3 study incorporating a bispecific T-cell engager to demonstrate an OS benefit in the first-line maintenance setting for ES-SCLC.

The results could have particular clinical relevance given the aggressive course of ES-SCLC and the potential for patients to experience disease progression before receiving subsequent lines of therapy. If supported by the complete data and regulatory review, the findings could move DLL3-directed therapy from the post-progression setting into first-line maintenance treatment.

Amgen plans to present detailed DeLLphi-305 findings at an upcoming international medical congress and discuss the results with regulatory authorities.

Source:

PRNewswire. Imdelltra® in combination with imfinzi® demonstrated landmark improvement in overall survival in first-line extensive stage small cell lung cancer. Accessed on: September 10, 2026. https://www.prnewswire.com/news-releases/imdelltra-in-combination-with-imfinzi-demonstrated-landmark-improvement-in-overall-survival-in-first-line-extensive-stage-small-cell-lung-cancer-302872305.html