Combining the targeted immunotherapy Imdelltra with Imfinzi reduced the risk of death by 58% compared to Imfinzi alone when used as a first-line maintenance treatment for patients with extensive-stage small cell lung cancer (ES-SCLC). The findings from the Phase III DeLLphi-305 clinical trial were presented on Saturday, October 24, 2026, at the European Society for Medical Oncology (ESMO) Congress in Madrid, Spain, and simultaneously published in The New England Journal of Medicine, according to Dana-Farber Cancer Institute and Reuters.

Led by international coordinating investigator Dr. Jacob Sands, Associate Chief of the Lowe Center for Thoracic Oncology at Dana-Farber Cancer Institute, the multicenter study evaluated whether adding Amgen's Imdelltra (tarlatamab) to AstraZeneca's Imfinzi (durvalumab) could extend survival in patients whose cancer had not progressed after initial chemotherapy and immunotherapy. Patients receiving the two-drug maintenance regimen lived a median of 21.1 months, compared to 12.7 months for those receiving Imfinzi alone, extending median survival by more than eight months for one of the most aggressive forms of lung cancer.

Inside the DeLLphi-305 Trial Results

The open-label, randomized Phase III DeLLphi-305 trial enrolled 563 patients with extensive-stage small cell lung cancer. Prior to entering the maintenance phase tested in the study, all participants had completed standard initial induction therapy—consisting of Imfinzi, platinum-based chemotherapy (carboplatin or cisplatin), and etoposide—without their disease progressing.

At a median follow-up of approximately 16 months, the planned interim analysis demonstrated a statistically significant improvement in overall survival, with a hazard ratio of 0.42, according to AstraZeneca. In clinical trial reporting, this hazard ratio translates to a 58% relative reduction in the risk of death during the follow-up period rather than a guarantee that an individual patient's chance of death drops by that exact percentage.

One-year survival rates showed a clear separation between the two treatment groups. Reuters reported that about 80% of patients in the combination arm were alive at one year, while AstraZeneca put the figure at an estimated 79%, compared to 53% in the Imfinzi-alone group, and CancerNetwork reported specific estimates of 79.4% versus 53.3%.

The combination also met its secondary goal of delaying cancer growth. At a median follow-up of 13.9 months, adding Imdelltra to Imfinzi reduced the risk of disease progression or death by 66% compared to Imfinzi alone. Median progression-free survival more than tripled, reaching 7.4 months for the combination group versus 1.9 months for the control group. At the one-year mark, an estimated 38% of patients on the dual therapy remained alive and progression-free, compared to 10% of those taking Imfinzi by itself.

Furthermore, the confirmed objective response rate was six times higher with the combination therapy at 26.4%, compared to 4.1% for Imfinzi alone. Among patients who responded to treatment, the median duration of response lasted 12.7 months in the combination arm versus 5.6 months in the control arm.

Why Extensive-Stage Small Cell Lung Cancer Is Difficult to Treat

Small cell lung cancer is a fast-growing malignancy that tends to spread to other organs much earlier than non-small cell lung cancer. According to Dana-Farber Cancer Institute, roughly 80% of patients diagnosed with small cell lung cancer already have extensive-stage disease by the time it is detected, meaning the tumor has spread widely throughout the lungs or to distant parts of the body.

For years, treatment advances in the initial frontline setting have been modest. Standard care begins with chemotherapy combined with an immune checkpoint inhibitor like Imfinzi, which helps the immune system recognize and attack tumor cells. Even with this regimen, median overall survival has historically hovered between 12 and 13 months, and tumors frequently relapse quickly during the maintenance phase.

Imdelltra belongs to a newer class of medications known as bispecific T-cell engagers. It works by binding simultaneously to the body's T-cells and to proteins on the surface of small cell lung cancer cells, bringing the immune cells directly into contact with the tumor to destroy it. While the U.S. Food and Drug Administration had previously approved Imdelltra as a later-line treatment for patients whose cancer returned after earlier therapies, DeLLphi-305 is the first Phase III trial to show an overall survival benefit when using a bispecific T-cell engager earlier, in the first-line maintenance setting.

"This trial is positive in every way. We have seen substantial improvement in median progression-free survival, substantial improvement in median overall survival, and we're improving the time of disease control substantially for a broader group of patients than what we've seen from any prior study and any prior treatment," Dr. Sands said in the Dana-Farber release. "This immunotherapy combination sets a new standard of care with tarlatamab plus durvalumab in the maintenance setting after induction chemotherapy plus durvalumab."

What This Means for Patients and Care Teams

One of the most clinically meaningful findings from the DeLLphi-305 study is that the survival benefit held steady across all prespecified patient subgroups. Importantly, this included patients whose cancer had already spread to the brain or liver—populations that typically face the steepest treatment hurdles and poorest prognoses.

"For a disease where durable survival has remained extremely difficult to achieve, the magnitude and consistency of benefit in DeLLphi-305 are striking," Dr. Sands stated in the AstraZeneca announcement. "Importantly, the benefit was seen across clinically relevant groups, including patients with brain metastases."

For patients and families navigating an extensive-stage small cell lung cancer diagnosis, it is helpful to understand how this regimen fits into the treatment timeline. The DeLLphi-305 trial did not replace initial chemotherapy. Instead, it tested the drug combination solely among patients who had already completed their initial rounds of platinum chemotherapy, etoposide, and Imfinzi without their disease worsening.

How is the Imdelltra and Imfinzi combination used in treatment?

The combination is used as a first-line maintenance therapy, not as the very first treatment given at diagnosis. Patients first receive standard induction therapy consisting of platinum chemotherapy, etoposide, and Imfinzi. If their cancer does not progress during that initial phase, Imdelltra is added alongside Imfinzi to help maintain disease control and delay relapse.

Does this benefit apply to every person diagnosed with ES-SCLC?

Because the study only randomized patients whose tumors remained stable or shrank during initial induction chemoimmunotherapy, the exact survival numbers apply specifically to patients who reach the maintenance phase without disease progression. It does not establish the same outcomes for patients whose cancer progresses during initial chemotherapy or those who cannot tolerate Imfinzi.

What questions remain as researchers track the data?

While AstraZeneca reported the primary survival metrics from the planned interim analysis and Reuters noted the presentation and publication of the dataset, oncologists will continue monitoring longer-term follow-up to see how durable the survival advantage remains over several years. Physicians and patients will also weigh detailed safety data, quality-of-life metrics, and potential side effects—such as immune-related reactions—when determining how to incorporate the maintenance regimen into clinical practice and updated treatment guidelines.

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