Interim results from the global phase 3 DeLLphi-305 trial, presented on October 24, 2026, at the European Society for Medical Oncology Congress 2026 in Madrid, Spain, and published in the New England Journal of Medicine, show that adding tarlatamab-dlle (Imdelltra; Amgen) to durvalumab (Imfinzi; AstraZeneca) as first-line maintenance therapy significantly prolonged median overall survival in patients with extensive-stage small-cell lung cancer (ES-SCLC) by over 8 months.
According to the study, the combination regimen resulted in a median overall survival of 21.1 months, surpassing the typical 12 to 13 months seen with first-line chemoimmunotherapy. The authors highlight the importance of optimizing first-line maintenance therapy for ES-SCLC patients, as many are unable to proceed to second-line therapy. As noted, “Many patients are unable to proceed to second-line therapy; therefore, improving first-line therapy represents an opportunity to improve outcomes.”
Study Design and Demographics
Between June 2024 and September 2025, a total of 563 patients were randomly assigned to either the tarlatamab-durvalumab combination (n = 282) or durvalumab alone (n = 281) at 175 sites across 29 countries. To be eligible, patients had to have an Eastern Cooperative Oncology Group performance status of 0 or 1, with no disease progression after 4 cycles of platinum-etoposide, including at least 3 cycles given with durvalumab. Patients with asymptomatic treated or untreated brain metastases were also allowed to participate. The primary endpoint was overall survival from randomization, while progression-free survival was the key secondary endpoint.
The study population lacked diversity, with Black patients underrepresented compared to their presence in the overall US population and among those with ES-SCLC. According to federal data, 8% of US patients with this type of lung cancer are Black. Similarly, Hispanic patients, who account for 2.3% to 3% of patients with ES-SCLC, were also underrepresented. In the combination group, the population was 57.8% White (163 patients), 38.7% Asian (109 patients), 1.4% Black (4 patients), and 1.8% other (5 patients), while the durvalumab group consisted of 64.4% White (181 patients), 32.7% Asian (92 patients), 1.4% Black (4 patients), and 1.4% other (4 patients).
The trial included never smokers, reflecting recent trends in clinical trials. In the combination arm, 19.1% of patients were current smokers (54 patients), 9.2% were never smokers (26 patients), and 71.3% were former smokers (201 patients), with 1 patient having missing data (0.4%).
The restriction to patients who did not progress after initial chemoimmunotherapy highlights the need to evaluate tarlatamab earlier in the treatment course. This is being addressed in the separate phase 3 DeLLphi-312 trial (NCT07005128), which is testing tarlatamab with durvalumab, carboplatin, and etoposide in untreated ES-SCLC and has already completed enrollment.
Regulatory Status and Monitoring Requirements
The FDA approved tarlatamab for adults with extensive-stage small-cell lung cancer who have progressed after chemotherapy. The agency granted full approval based on the DeLLphi-304 trial, which showed a median overall survival of 13.6 months compared to 8.4 months with chemotherapy.
Administration requires a 60-minute intravenous infusion. The first dose is 1 mg, followed by 10 mg on days 8 and 15 and then every two weeks. The label carries a boxed warning for cytokine release syndrome and neurologic toxicity.
Monitoring requirements were updated in September 2026. This change supports the use of outpatient administration.
Safety Profile
Grade 3 or higher adverse events were reported in 46.8% of patients receiving the combination, compared to 40.6% of those receiving durvalumab alone. Serious adverse events occurred in 41.8% of the combination group and 31.7% of the durvalumab group. Fatal adverse events were similar across both arms, affecting 4.6% and 4.7% of patients, respectively.
Cytokine release syndrome was the most common treatment-related issue, affecting 49.6% of patients receiving tarlatamab. However, most cases were mild, with 41.8% being grade 1 events and 7.4% being grade 2 events. Only one grade 3 event was reported, and no fatal events were linked to this side effect. The median onset of symptoms was 22.5 hours after infusion.
Immune effector cell–associated neurotoxicity syndrome (ICANS) was rare, affecting 1.1% of patients in the combination arm, with no instances of grade 3 or higher severity. Dysgeusia, or a change in taste, was reported by 48.9% of patients. Adverse events led to discontinuation of tarlatamab in 5.7% of patients.
Regulatory Path and Future Directions
In September 2026, the FDA shortened the recommended monitoring period after the first two doses from 22 to 24 hours to 6 to 8 hours, based on safety data from the DeLLphi-305 trial.
Amgen officials stated that they are moving with urgency to share these results with global regulatory authorities. The companies estimate that a first-line maintenance indication could benefit approximately 23,000 patients in the United States. They also noted that the shorter monitoring protocol could support outpatient administration of the medication.
As of mid-November, Amgen had not announced a regulatory submission for the combination. The trial’s open-label design and restriction to patients who did not progress after induction therapy may be considered by regulators. However, a statistically significant overall survival benefit at a prespecified interim analysis provides a strong foundation for a filing. Meanwhile, the phase 3 DeLLphi-312 trial continues to test the combination in untreated patients.
