November 2nd, 2026
Summary by Warren Froelich
Adding the bispecific T-cell engager drug tarlatamab to durvalumab (durva) as first-line maintenance following initial therapy helped patients with extensive-stage small cell lung cancer (ES-SCLC) better control their disease, manage side effects and live longer, according to a global DeLLphi-305 patient study.
Specifically, the drug combination extended survival among these patients beyond 8 months while more than tripling progression-free survival when compared to those given durva alone. Some 38% of patients on tarlatamab and durva were still controlling their disease at 1 year, compared to just 10% on durva alone.
The findings, presented during the European Society for Medical Oncology (ESMO) Congress 2026 meeting from October 23–25 in Madrid, Spain, and simultaneously published in the New England Journal of Medicine, were characterized by the researchers as “unprecedented” and “remarkable,” representing a new standard of care for these patients.
“With an unprecedented improvement in both overall survival and median progression-free survival, along with a manageable toxicity profile, I expect that the data from this trial will change the standard of care to incorporate tarlatamab with durvalumab in the maintenance setting treatment for first-line extensive-stage small cell lung cancer,” said study principal investigator Jacob Sands MD, Associate Chief of the Lowe Center for Thoracic Oncology at the Dana-Farber Cancer Institute in Boston.
“In a disease where progress has been very limited and responses often do not last, this is incredibly encouraging,” he added in an interview.
According to the National Institutes of Health, SCLC accounts for about 10%–15% of all lung cancers, with the remainder of cases characterized as a generally less aggressive non-small cell lung cancer. In the U.S. alone, an estimated 30,000 new cases of SCLC will be diagnosed this year, with predicted deaths reaching 16,249 people.
Approximately two-thirds of patients with SCLC are diagnosed with extensive-stage SCLC, with a median survival between 10–13 months. This subset of lung cancer is an aggressive, fast-growing form of the disease that has spread beyond one side of the chest to the other lung and/or distant organs (such as the brain, liver, or bone), or fluid surrounding the lung or heart.
Chemotherapy remained the standard to treat ES-SCLC for decades, though several years ago immunotherapy—through checkpoint inhibitors—were introduced, an important step forward. But many patients still fail to experience long-term benefit, remaining too sick for further therapy once the disease has returned.
Prompted by a high “unmet need” for these patients, a worldwide search continues for a more effective early treatment. Among those efforts is the Phase 3 DeLLphi-305 study, sponsored by Amgen with partial funding by AstraZeneca.
At the heart of the trial is tarlatamab—a “bi-specific T-cell engager” that’s designed to bind to CD3 proteins on immune T-cells and to DLL3 (Delta-like ligand 3) found on the cell surfaces of about 85% patients with SCLC. These DLL3 proteins are restricted largely to tumor cells, with minimal presence in normal adult tissues, making it an attractive drug target.
Durvalumab, the study’s partner drug, is an immunotherapy that blocks the programmed death ligand 1 (PD-L1) on tumor cells, reactivating T cells to recognize and destroy cancer cells and slow tumor growth.
As outlined, some 563 ES-SCLC patients who completed initial treatment with durva, platinum-based chemotherapy and etoposide were enrolled in the DeLLphi-305 study and randomly selected 1:1 to receive the drug combination tarlatamab plus durva or just durva alone as first-line maintenance therapy until disease progression or unacceptable toxicity. Patients with brain and liver metastases, historically linked to poorer outcomes, also were included in the study.
Nearly 80% of patients on the drug combination were alive 1 year following the start of therapy versus 53% given only durva. At a median follow-up of 13.9 months, tarlatamab plus durva reduced the risk of disease progression or death by 66% compared to the control, with a median progression-free survival of 7.4 months versus 1.9 months.
Median overall survival was 21.1 months for the drug combination compared to 12.7 months for durva alone. More patients experienced tumor shrinkage, with an objective response rate of 25.4% with the combination, compared to 4.1% with durva alone. Overall and progression-free survival benefits were observed across pre-specified subgroups, including patients with brain or liver metastases.
“Importantly, the treatment did not appear to add substantially more toxicity and was consistent with, if not less than, the side effects already seen with tarlatamab, which is generally more manageable than many chemotherapy-based approaches,” Sands said.
Side effects from the combination therapy were consistent with those experienced with individual agents, though some were more frequent in the combination. About 21% of patients on the combination therapy experienced grade 3 or high adverse events compared to about 11% for those given durva alone. The most common grade 3 or greater diagnoses included low neutrophil count, decreased appetite, fatigue, and weight loss.
Nearly half of the patients given the drug combination experienced mild cytokine release syndrome (CRS), frequently seen as a side effect of immunotherapy. Only 1.1% of patients on the drug combination experienced mild immune effector cell-associated neurotoxicity syndrome (iCANS).
“The median progression-free survival was surprisingly long to me.” Sands said, when asked if he was surprised by any other results. “We are not just seeing a modest improvement measured in months. We are seeing a meaningful extension of disease control, with a substantial subset of patients still benefiting at 1 year.”
Sands added the “most important next step” is to continue to follow patients longer to better understand the durable effects of the drug combination. A second important step is to better understand who benefits most and why some cancers eventually stop responding.
“Finally, these results support moving effective therapy earlier in the course of the disease,” Sands said. “Many patients with small cell lung cancer never make it to second-line treatment, so bringing a treatment like tarlatamab into the first-line maintenance setting could have a major impact.
“The next step is to build on the progress so that more patients not only respond, but experience disease control that lasts for years.”
Warren Froelich is a contributing writer.