A combination of tarlatamab-dlle (Imdelltra; Amgen) and durvalumab (Imfinzi; Amgen) produced a statistically significant and clinically meaningful improvement in overall survival (OS) compared with durvalumab alone as first-line maintenance therapy for extensive-stage small cell lung cancer (ES-SCLC), according to topline results from a phase 3 trial.
DeLLphi-305 Trial Details
The DeLLphi-305 study (NCT06211036) tested tarlatamab, a DLL3xCD3 bispecific T-cell engager (BiTE) developed by Amgen, in patients with ES-SCLC whose disease had not progressed after induction treatment with durvalumab, platinum-based chemotherapy, and etoposide. The trial randomized 563 patients 1:1 to receive tarlatamab plus durvalumab or durvalumab alone until disease progression or unacceptable toxicity.
In addition to meeting its primary OS end point at a prespecified interim analysis, the combination showed statistically significant and clinically meaningful improvements in progression-free survival (PFS) and objective response rate, the trial’s secondary end points.
First BiTE to Show Benefit in Maintenance Setting
This is the first phase 3 trial of a BiTE therapy to demonstrate an OS benefit in first-line maintenance treatment of ES-SCLC, an aggressive cancer that accounts for 13% to 15% of the more than 2.6 million lung cancer cases diagnosed worldwide each year. Despite advances in frontline therapy, outcomes remain poor: median survival is approximately 1 year from the start of first-line maintenance treatment, and only about 40% of patients go on to receive second-line therapy.
DeLLphi-305 was designed to build on that earlier-line evidence, evaluating tarlatamab in combination with an anti-PD-L1 checkpoint inhibitor even earlier in the treatment course. Amgen said it plans to present detailed DeLLphi-305 data at an upcoming medical congress and to share the results with regulatory authorities.
Aggressive Disease Requires Early Intervention
“Given the aggressive nature of small cell lung cancer, many patients quickly relapse on current therapy and never reach second-line treatment,” said Jacob Sands, MD, associate chief of the Lowe Center for Thoracic Oncology at Dana-Farber Cancer Institute, in a statement. “These patients do not have time to wait, making substantial progress in the first-line setting critically important. In my career treating people with extensive-stage small cell lung cancer, these are among the most compelling survival results I have seen, indicating the potential to reshape the natural history of small cell lung cancer. DeLLphi-305 represents an unprecedented milestone and suggests we may be entering a new era where meaningfully longer survival is possible for more patients.”
Safety Profile Consistent With Known Risks
The safety profile of tarlatamab plus durvalumab was consistent with the known safety profiles of the individual agents, and no new or unexpected safety signals emerged in DeLLphi-305. Per the study protocol, patients were monitored in a health care setting for 1 to 2 hours after tarlatamab infusions on cycle 1, day 1, and cycle 1, day 8 (6 to 8 hours in certain regions, including Europe). Tarlatamab carries a boxed warning for cytokine release syndrome and neurologic toxicity, including immune effector cell-associated neurotoxicity syndrome.
Tarlatamab is already approved in the US for adults with ES-SCLC whose disease has progressed on or after platinum-based chemotherapy, a label the FDA converted from accelerated to traditional approval in November 2025 based on the phase 3 DeLLphi-304 trial, in which tarlatamab reduced the risk of death by 40% and extended median OS by more than 5 months compared with chemotherapy in the second-line setting.
