Tarlatamab plus durvalumab cut death risk 58% in first-line small cell lung cancer

Tarlatamab (Imdelltra), which already has accelerated FDA approval for previously treated extensive-stage small cell lung cancer, reduced the risk of death by 58% when combined with durvalumab (Imfinzi) as first-line maintenance in the Phase 3 DeLLphi-305 trial, Amgen announced. The data were shown during the ESMO 2026 Presidential Symposium and published in The New England Journal of Medicine.

DeLLphi-305 was a global, randomized, open-label Phase 3 trial that enrolled 563 patients with extensive-stage small cell lung cancer whose disease had not progressed after induction therapy with durvalumab, a platinum drug, and etoposide. Participants were assigned equally to receive tarlatamab plus durvalumab or durvalumab by itself, continuing treatment until progression or unacceptable toxicity. The primary outcome measure was overall survival.

After roughly 16 months of median follow-up, median overall survival was 21.1 months in the combination group versus 12.7 months in the durvalumab-alone group (hazard ratio 0.42; 95% confidence interval 0.32 to 0.54). At 12 months, about 80% of patients in the combination arm were still alive, compared with 53% in the durvalumab-alone arm. The trial also reported a median progression-free survival of 7.4 months with the combination and 1.9 months with durvalumab alone, representing a 66% lower risk of disease progression or death (hazard ratio 0.34; 95% CI 0.28 to 0.42); this analysis used a median follow-up of 13.9 months. The objective response rate was 26.4% with the combination and 4.1% with durvalumab alone.

The survival improvements were seen in all the protocol-defined patient subgroups that were examined, such as those with brain or liver metastases. Treatment-related side effects of grade 3 or above were reported in 20.9% of patients on the combination and 10.8% of those on durvalumab alone. Cytokine release syndrome was reported in 49.6% of patients who received tarlatamab; most events were grade 1 (41.8%) or grade 2 (7.4%), with one grade 3 event and no grade 4 or higher events. Immune effector cell-associated neurotoxicity syndrome occurred in 1.1% of tarlatamab-treated patients, with no grade 3 or higher events. Patients were observed in a clinical facility for one to two hours after the first two tarlatamab infusions, and for six to eight hours in selected regions such as Europe.

Amgen also reported longer follow-up data from its DeLLphi-303 and DeLLphi-304 trials. In DeLLphi-303, with a median follow-up of 30.8 months, the median overall survival from the beginning of first-line maintenance was 37.9 months for tarlatamab plus standard anti-PD-L1 therapy, and 58.1% of patients were alive at two years. In DeLLphi-304, with 23 months of follow-up, patients treated with tarlatamab lived a median of 13.6 months versus 8.4 months with chemotherapy, a 38% reduction in the risk of death.

The Clinical Trial Vanguard noted that these Phase 3 overall survival results put regulatory submissions for the first-line maintenance indication in a different position. Amgen said it plans to submit the results to regulators worldwide without delay.

Update, October 25, 2026

Amgen's release also lists the most frequent grade 3 or higher treatment-related adverse events in the combination arm: fall in neutrophil count (3.2%), reduced appetite (2.1%), neutropenia (2.1%), asthenia (1.8%) and weight loss (1.8%). For the one-year survival estimate, the company gives confidence intervals of 74.2 to 83.7 percent with tarlatamab plus durvalumab and 47.3 to 59.0 percent for durvalumab alone. The trial enrolled patients with treated or untreated asymptomatic brain metastases at baseline. Amgen sponsored the study, and AstraZeneca supplied partial funding and durvalumab.

For DeLLphi-303, the confidence interval for the 37.9-month median overall survival was 22.5 months to not estimable. DeLLphi-304's updated analysis had a hazard ratio of 0.62 with a 95 percent confidence interval of 0.51 to 0.76. Amgen R&D chief Jay Bradner said the company is moving quickly to provide the data to regulators worldwide. Amgen will discuss the results on an investor call on Oct 24 at 8:30 p.m. CEST.