Adding tarlatamab to durvalumab as first-line maintenance therapy in patients with extensive-stage small cell lung cancer improved overall survival by more than 8 months.

Patients who received the combination had a median overall survival of 21.1 months compared with 12.7 months with durvalumab alone, according to new data from a the phase 3 DeLLphi-305 trial.

The findings establish tarlatamab plus durvalumab in the maintenance setting as “a new standard of care in the treatment of extensive-stage small cell lung cancer,” reported Jacob Sands, MD, of Harvard University in Boston, at the European Society for Medical Oncology Annual Meeting 2026 in Madrid. 

Sands’ presentation of the open-label DeLLphi-305 randomized clinical trial prompted loud applause from the audience. The findings were published simultaneously in the New England Journal of Medicine.

Invited discussant Stephen Liu, MD, of Georgetown University in Washington, DC, called the results “remarkable,” with reported 12-month survival rates that “far surpass” previous standards.

Small cell lung cancer (SCLC) often relapses following a robust initial response to chemotherapy, and outcomes in such cases are poor.

Tarlatamab previously was shown to boost survival in patients with relapsed disease compared with chemotherapy alone, and consequently was approved for treatment after progression in both the United States and Europe. The drug has not been approved for first-line maintenance in extensive-stage small cell lung cancer (ES-SCLC) in patients who have not progressed after induction with chemoimmunotherapy. 

Previously, the longest median overall survival seen with first-line treatment of ES-SCLC was 13.2 months, when lurbinectedin was added to atezolizumab maintenance in the phase 3 IMforte trial, according to a statement from ESMO.

In DeLLphi-305, Sands and colleagues randomly assigned 563 patients to receive tarlatamab–durvalumab or durvalumab alone following induction with four cycles of platinum-etoposide and durvalumab.

On the first day of cycle 1 of maintenance therapy, patients received 1 mg of tarlatamab IV. On day 8 and 15, they received 10 mg IV, followed by 10 mg IV every 2 weeks until progression or unacceptable toxicity. Durvalumab was given at 1500 mg IV every 4 weeks. 

The median follow-up of about 16 months was “not the final median overall survival,” said Sands.

New phase 3 trial data showed that receiving the combination cut the risk of death by 58% compared to taking durvalumab alone, significantly extending how long patients lived (P < .001).

At 12 months, 79.4% of patients on tarlatamab and durvalumab were alive, compared with 53.3% of those receiving durvalumab alone. Median progression-free survival was 7.4 vs 1.9 months, respectively, and objective response rates were 26.4% and 4.1%. 

“Across all subgroups, there appears to be benefits from [adding] tarlatamab with durvalumab,” Sands told the conference.

Grade 3 or higher treatment-emergent adverse events occurred in 46.8% of patients on the combination vs 40.6% with durvalumab alone. There were 13 deaths in each group, with two fatalities deemed related to treatment in the durvalumab arm. 

Immune-effector cell-associated neurotoxicity syndrome (ICANS) occurred in three patients on the combination (1.1%) but did not lead to discontinuation of the drug. Half of the patients receiving tarlatamab developed cytokine-release syndrome (CRS), but only one case was grade 3 or above. 

One patient discontinued tarlatamab due to CRS. Most CRS cases were resolved with supportive care and antipyretics.

Liu called the safety data “reassuring,” and noted that a change to the package insert “eliminates one of the major barriers to delivery and improves access to this important drug.”

Until recently, an observation period of 22-24 hours following the first two tarlatamab infusions was recommended, vs the current 6-8 hours monitoring time. It is shorter during later cycles, Liu explained.

Expressing enthusiasm about the treatment regimen, he said, “These data do more than show us a better way to treat patients with small cell lung cancer. They provide our patients with real, credible hope in a disease where hope has been in short supply.”

The trial was sponsored by Amgen. Sands and Liu both reported financial ties to the company.