Amgen Cancer Drug Combination Cuts Death Risk 58% in Phase 3 Trial

Amgen said Saturday that adding its cancer drug Imdelltra to AstraZeneca’s Imfinzi lowered the relative hazard of death by 58% in a Phase 3 study of patients with extensive-stage small cell lung cancer. The result came from a planned interim analysis of DeLLphi-305, which tested the two medicines as maintenance treatment after an initial course of chemotherapy and immunotherapy.

Patients receiving the two-drug regimen had median overall survival of 21.1 months, compared with 12.7 months for those given Imfinzi alone. Estimated survival at one year was 79% with the regimen and 53% in the comparison group, a difference of 26 percentage points. The study involved 563 patients whose cancer had not progressed on their initial treatment.

The 58% figure reflects an overall-survival hazard ratio of 0.42, with a 95% confidence interval of 0.32 to 0.54 and a reported P value below 0.001. It describes the relative rate of death during follow-up, not an absolute 58-percentage-point reduction in deaths. The findings were detailed in Amgen’s October 24 announcement and presented at the European Society for Medical Oncology congress in Madrid, alongside publication in The New England Journal of Medicine.

How the trial tested earlier use of Imdelltra

DeLLphi-305 enrolled patients with extensive-stage disease who had first received Imfinzi, a platinum-based chemotherapy drug and etoposide. Once they completed that initial treatment without their cancer progressing, 282 were assigned to continue with Imfinzi plus Imdelltra and 281 to receive Imfinzi alone. The global study was randomized but open-label, meaning patients and doctors knew which treatment was being given.

That timing is central to the result. Imdelltra, also known as tarlatamab-dlle, has been used in patients whose cancer worsened after chemotherapy. DeLLphi-305 instead investigated whether adding it before such progression could extend the period of disease control and, more importantly, patients’ lives. Overall survival was the primary endpoint, so the study was designed to measure more than a change in scan results.

The trial also met its key progression-free survival endpoint. Median time before disease progression or death was 7.4 months with Imdelltra and Imfinzi, versus 1.9 months with Imfinzi alone. The progression-or-death hazard ratio was 0.34, equivalent to a 66% relative reduction, after a median follow-up of 13.9 months for that endpoint. At one year, an estimated 38% of patients in the two-drug arm remained alive without progression, compared with 10% in the control arm.

Among participants with measurable disease who were evaluated for tumor response, the confirmed response rate was 26.4% with the two medicines and 4.1% with Imfinzi alone. AstraZeneca reported that median duration of response was 12.7 months versus 5.6 months. These response findings support the disease-control results, although they were assessed in a smaller group than the full survival population.

The drugs work through different immune mechanisms. Imdelltra is designed to connect DLL3 on small cell lung cancer cells with CD3 on immune T cells, helping those cells attack the tumor. Imfinzi, or durvalumab, blocks the PD-L1 checkpoint pathway that can dampen immune responses. The trial therefore examined whether T-cell engagement could add benefit to maintenance treatment with an established checkpoint inhibitor.

Amgen reported that the survival advantage extended across prespecified patient subgroups, including people with brain or liver metastases. The study included patients with treated or untreated asymptomatic brain metastases at baseline. Subgroup consistency is encouraging, but the trial’s headline numbers describe the overall eligible population, not a separately proven 58% benefit for every individual subgroup.

Additional toxicity and monitoring requirements

Longer survival came with a higher rate of severe treatment-related side effects. Events graded 3 or higher occurred in 20.9% of patients receiving Imdelltra plus Imfinzi, compared with 10.8% on Imfinzi alone. Among the severe reactions reported with the regimen were reductions in neutrophil counts, reduced appetite, weakness and weight loss. AstraZeneca said there were no treatment-related deaths in the study.

Cytokine release syndrome, an inflammatory reaction associated with T-cell-engaging medicines, was reported in 49.6% of patients given Imdelltra. Most cases were mild or moderate: 41.8% were grade 1 and 7.4% were grade 2. Amgen reported one grade 3 case, representing 0.4% of patients, and no grade 4 or higher cases. Another known risk, immune effector cell-associated neurotoxicity syndrome, occurred in 1.1% of recipients, with no grade 3 or higher cases in this trial.

The study required patients to be observed in a healthcare setting after their first two Imdelltra infusions, normally for one to two hours and for six to eight hours in certain regions, including Europe. That supervision adds a practical consideration beyond the efficacy figures: using the regimen involves infusion capacity and early-treatment monitoring rather than simply continuing the existing maintenance drug.

The safety findings should not be read as eliminating the medicine’s established risks. The U.S. prescribing information for Imdelltra carries boxed warnings for potentially life-threatening cytokine release syndrome and neurological toxicity, including neurotoxicity associated with immune effector cells. DeLLphi-305 also remains an interim, open-label analysis. The reported survival effect is statistically strong, but longer follow-up will provide a fuller picture of the duration of benefit and longer-term tolerability.

The regulatory opportunity is an earlier treatment setting

The new findings could support a broader role for Imdelltra, but they do not themselves authorize the maintenance regimen. The U.S. Food and Drug Administration granted traditional approval in November 2025 for adults with extensive-stage small cell lung cancer whose disease has progressed on or after platinum-based chemotherapy. That decision followed the drug’s accelerated approval in May 2024 and concerned treatment after progression, not the first-line maintenance setting studied in DeLLphi-305.

The 2025 decision was supported by the separate Phase 3 DeLLphi-304 trial, in which Imdelltra was compared with chemotherapy among patients whose disease had already progressed. Median survival in that study was 13.6 months with Imdelltra and 8.3 months with the chemotherapy options. Those results are not directly comparable with DeLLphi-305’s survival figures because the trials enrolled patients at different points in their treatment and used different control regimens.

For Amgen, the commercial significance of DeLLphi-305 lies in the possibility of moving an approved medicine earlier in the course of a difficult-to-treat cancer. First-line maintenance would represent a different use and patient group from the existing U.S. label. Any wider adoption would depend on regulatory decisions, prescribing guidance and the balance of survival benefit against safety and treatment burden. The company has not reported a new drug-sales estimate tied to these findings.

Amgen had already said in September that DeLLphi-305 met its primary overall-survival endpoint at the prespecified interim analysis, without disclosing the detailed survival figures. The October presentation provides the magnitude of the improvement and the accompanying side-effect data. The company said it plans to share the results with regulatory authorities worldwide, but announced no specific submission date or approval timetable for the maintenance use.