Amgen and AstraZeneca combo cuts lung cancer death risk by 58 percent in Phase 3 trial

Extensive-stage small cell lung cancer has long been the most unforgiving diagnosis in thoracic oncology. The disease has usually spread well beyond the lung by the time it is found, it responds quickly to chemotherapy and then returns quickly, and for decades patients and clinicians have measured the benefit of new treatments in weeks rather than years. Platinum chemotherapy paired with etoposide was the backbone of first-line care for a generation, and the arrival of immunotherapy added months, not years, to the median.

That baseline is what makes the numbers released on October 24, 2026 worth examining closely. Amgen and AstraZeneca disclosed full results from DeLLphi-305, a Phase 3 trial testing two immunotherapies together as maintenance treatment for patients whose cancer had not progressed after standard induction. The data were presented in a Presidential Symposium at the European Society for Medical Oncology Congress 2026 in Madrid and published simultaneously in the New England Journal of Medicine.

The two medicines work through entirely different mechanisms. Tarlatamab, sold by Amgen as Imdelltra, is a bispecific T cell engager that binds DLL3 on tumor cells and CD3 on T cells, physically drawing immune cells into contact with cancer cells. Durvalumab, AstraZeneca's Imfinzi, blocks PD-L1. Neither is a conventional chemotherapy, and DeLLphi-305 is one of the clearest tests yet of whether two immune approaches can be layered in this disease without unacceptable toxicity.

Amgen already sells Imdelltra in later lines of treatment. The drug posted $288 million in sales in the second quarter, up 115% year over year, and $627 million in global sales in 2025. DeLLphi-305 is the company's attempt to move the medicine earlier in the treatment sequence, where far more patients can be reached and where the commercial prize is considerably larger.

Key Facts

CNBC reported on October 24, 2026, that adding Imdelltra to Imfinzi cut the risk of death by 58% in extensive-stage small cell lung cancer and extended median overall survival to 21.1 months, compared with 12.7 months for Imfinzi alone. Nearly 80% of patients who started both drugs were alive at one year, versus 53% of those receiving Imfinzi by itself.

Amgen announced on October 24, 2026, that the interim analysis produced a hazard ratio for death of 0.42, with a 95% confidence interval of 0.32 to 0.54 and a P value below 0.001, at a median follow-up of about 16 months. The company described the gain as an improvement of more than eight months in median survival. Amgen's chief medical officer, Dr. Paul Burton, said the data could almost convert the disease into a chronic condition.

OncLive reported on October 24, 2026, that DeLLphi-305 randomized 563 patients in a 1:1 ratio, 282 to the combination and 281 to durvalumab alone, after four cycles of platinum chemotherapy plus etoposide and durvalumab. Median age was 65.0 years, 19.5% of combination patients had current or prior brain metastases versus 19.9% on the control arm, and 31.2% versus 33.8% had liver metastases. The interim analysis was triggered at 243 deaths, and at the July 7, 2026 data cutoff, 43.6% of combination patients remained on treatment versus 11.4% of those on durvalumab alone.

AstraZeneca said on October 24, 2026, that the combination reduced the risk of disease progression or death by 66%, with a hazard ratio of 0.34 and a confidence interval of 0.28 to 0.42. Median progression-free survival was 7.4 months versus 1.9 months, and 38% of combination patients were alive without progression at one year versus 10%. Confirmed objective response was 26.4% versus 4.1%, and median duration of response was 12.7 months versus 5.6 months.

Safety data were consistent with the known profiles of both drugs. Grade 3 or higher treatment-related adverse events occurred in 20.9% of combination patients versus 10.8% of those on durvalumab alone. Cytokine release syndrome occurred in 49.6% of Imdelltra patients versus 1.4%, and it was mostly grade 1 (41.8%) or grade 2 (7.4%), with one grade 3 event and none grade 4 or higher. Patients on the combination received tarlatamab 10 mg every two weeks plus durvalumab 1500 mg every four weeks.

Analysis

The headline number is dramatic, but the detail that carries the most weight is the shape of the survival curve rather than its median. A one-year survival rate of roughly 79% against 53% means the separation between the arms appears early and holds, and a progression-free survival of 7.4 months against 1.9 months suggests the combination is doing real work in the maintenance setting rather than simply shifting a few patients later into the calendar. AstraZeneca described the result as the longest benefit ever reported in extensive-stage disease in a Phase 3 trial.

What this really means is that small cell lung cancer, a disease that has resisted almost every attempt to extend survival beyond the first year, now has a credible candidate for a new first-line maintenance standard, and the effect size is large enough that payers, regulators and clinicians will all have to take it seriously. The consistency of benefit across subgroups matters here. Dr. Jacob Sands, associate chief of the Lowe Center for Thoracic Oncology at Dana-Farber Cancer Institute and the trial's lead investigator, said the benefit held in patients whose cancer had spread to the brain or liver, the two sites that most often define a poor prognosis.

The caveats are real and should not be buried. This is an interim analysis, not a final one, and the confidence interval around the survival hazard ratio, while well below 1, still spans a meaningful range. Follow-up sits at roughly 16 months, which is enough to see a median but not enough to know whether the tail of the curve flattens or decays. The trial also enrolled patients with ECOG performance status of 0 to 1 whose disease had not progressed after induction, a fitter population than the full extensive-stage universe, so the results cannot be generalized without care to patients who struggle through initial chemotherapy.

Toxicity is the second constraint. Cytokine release syndrome appeared in about half of patients exposed to tarlatamab, even if almost all of it was low grade, and grade 3 or higher treatment-related events roughly doubled from 10.8% to 20.9%. That is manageable in centers that know the drug, and Imdelltra has been used in later lines long enough for those protocols to exist, but a maintenance regimen given to a broad first-line population demands monitoring discipline that smaller hospitals may struggle to reproduce immediately.

Why It Matters

Small cell lung cancer has absorbed a long series of disappointments, and the bar for excitement should be set high. On the measures that regulators and clinicians actually use, DeLLphi-305 clears that bar. A 58% reduction in the risk of death, with 12-month survival moving from 53% to about 79%, is a magnitude of benefit rarely seen in this indication, and it arrives in a treatment that is added to an existing immunotherapy backbone rather than replacing it.

The strategic consequences for both companies are substantial. AstraZeneca's Imfinzi keeps its place at the center of first-line therapy and gains a partner that appears to amplify it, while Amgen gets a route into the maintenance setting, where duration of treatment and patient volume are far larger than in relapsed disease. With Imdelltra at $627 million in 2025 global sales and growing 115% year over year in the second quarter, the combination gives Amgen a defensible argument for earlier use.

For patients, the practical change is the possibility of a maintenance phase that meaningfully extends time without progression. Progression-free survival of 7.4 months against 1.9 months is not a cure, and no one involved is claiming one, but it changes what a patient can plan for after finishing induction chemotherapy. That is the measure many people with this diagnosis care about most.

Next Up

The next data points to watch are the final analysis of DeLLphi-305 and the separate DeLLphi-303 follow-up, which showed a median overall survival of 37.9 months from the start of first-line maintenance, with 58.1% of patients alive at two years. If that kind of tail is confirmed in the randomized setting, the case for the combination becomes considerably stronger. Regulatory submissions and pricing decisions will follow the published data, and both companies will need to address the monitoring burden that comes with cytokine release syndrome.

Dr. Sands said the outcomes support the combination as a new standard of care in this setting. Whether the oncology community adopts that framing quickly will depend less on the survival curve, which is striking, than on how reliably community practices can deliver a two-drug immune regimen with a known risk of cytokine release. The ESMO presentation and the New England Journal of Medicine paper give clinicians the material to start that debate now.