Amgen's IMDELLTRA Cuts Death Risk 58% in Small-Cell Lung Cancer Study

Key Points

• IMDELLTRA plus IMFINZI reduced the risk of death by 58% versus IMFINZI alone in the Phase III DeLLphi-305 trial for extensive-stage small-cell lung cancer, with a statistically significant overall-survival hazard ratio of 0.42.
• The combination also improved progression-free survival, extending median time from 1.9 to 7.4 months, and raised the response rate from 4% to 26%. Benefits were observed across analyzed subgroups, including patients with brain or liver metastases.
• Adverse events increased but were generally manageable, with no fatal treatment-related events reported. Amgen plans to submit the results to regulators globally and is evaluating IMDELLTRA in additional treatment settings and cancers expressing DLL3.

Amgen NASDAQ: AMGN presented Phase III data at the European Society for Medical Oncology Congress 2026 showing that its DLL3-targeting BiTE therapy IMDELLTRA, when added to durvalumab maintenance treatment, improved survival outcomes for patients with extensive-stage small-cell lung cancer whose disease had not progressed after initial chemoimmunotherapy.

The DeLLphi-305 study compared IMDELLTRA plus AstraZeneca’s IMFINZI, or durvalumab, against IMFINZI alone in the first-line maintenance setting. Patients were randomly assigned after completing four cycles of induction chemotherapy and immunotherapy and had stable disease or better at enrollment. The primary endpoint was overall survival.

Charles Rudin, director of Memorial Sloan Kettering Cancer Center, said the trial showed an overall-survival hazard ratio of 0.42, representing a 58% reduction in the risk of death for the combination versus IMFINZI alone. The result had a P value of less than 0.001, according to the presentation.

“The survival benefit really extends to all subgroups analyzed, including those patients with brain metastases, liver metastases, and irrespective of the chemotherapy combination used in induction,” Rudin said. He characterized the results as “practice-changing data.”

Progression-Free Survival and Response Results

Progression-free survival was also improved in DeLLphi-305. Median progression-free survival was 7.4 months for patients receiving the IMDELLTRA combination, compared with 1.9 months for those receiving IMFINZI alone. The progression-free survival hazard ratio was 0.34, reflecting a 66% reduction in the risk of disease progression or death, with a P value below 0.001.

The overall response rate in the maintenance setting was 26% for the combination, compared with 4% for IMFINZI alone. More than half of responding patients in the combination group remained in response one year later, Rudin said. At the data cutoff, 44% of patients on the combination remained on treatment, versus 11% in the control group.

The study enrolled patients with treated or untreated asymptomatic brain metastases. About 20% of enrolled patients had brain metastases and roughly one-third had liver metastases, with baseline characteristics described as balanced between the treatment arms.

The findings were presented during an ESMO presidential symposium and were published concurrently in The New England Journal of Medicine, according to Rudin.

Safety Profile

Rudin said adverse events increased with the addition of a second therapy but were manageable. Treatment-related adverse events resulting in treatment discontinuation or treatment holds occurred in 3% of patients for each of the two medicines in the combination arm. No fatal events attributable to treatment were reported for the combination.

Two key potential toxicities associated with BiTE therapies are cytokine release syndrome, or CRS, and immune effector cell-associated neurotoxicity syndrome, or ICANS. In DeLLphi-305, there was one Grade 3 CRS event in the combination arm and no Grade 3 or higher ICANS events, Rudin said.

Jean-Charles Soria, Amgen’s senior vice president of oncology global development, said the maintenance setting was selected in part because patients had already undergone tumor reduction with induction chemoimmunotherapy. He said this approach was expected to support both efficacy and tolerability.

Broader IMDELLTRA Development

IMDELLTRA is already approved in more than 15 markets for second-line or later extensive-stage small-cell lung cancer, Amgen said. The company reported that more than 18,000 patients have been treated since launch. In the U.S., the therapy is available at more than 2,000 sites of care, with over 65% of sites that have used the medicine located in community settings.

Amgen said it plans to rapidly submit the DeLLphi-305 data to regulators globally. The company is also studying IMDELLTRA in first-line induction and maintenance therapy in the Phase III DeLLphi-312 study and after concurrent chemoradiotherapy for limited-stage disease in the Phase III DeLLphi-306 trial.

Other company-sponsored work includes studies of alternative dosing schedules, subcutaneous administration and combinations with antibody-drug conjugates. Soria said Amgen also plans to evaluate the treatment in neuroendocrine cancers and other malignancies that express DLL3.

Kaveh Niksefat, Amgen’s senior vice president of global marketing and access, said the median treatment duration in DeLLphi-305 was 46 weeks, compared with 18 weeks in the company’s second-line DeLLphi-304 trial. He also cited reduced monitoring requirements, including one to two hours of monitoring in DeLLphi-305, as a potential factor supporting expanded access if the therapy moves into earlier treatment settings.

About Amgen (NASDAQ:AMGN)

Amgen Inc is a biotechnology company that discovers, develops, manufactures and delivers medicines for serious illnesses. Its research focuses on areas including oncology, cardiovascular disease, inflammation, bone health, nephrology and neuroscience.

The company's products include biologic and specialty medicines such as Enbrel for inflammatory diseases, Prolia and Evenity for osteoporosis, Xgeva for skeletal-related complications, Repatha for cardiovascular risk reduction, Otezla for inflammatory conditions, Tezspire for severe asthma, Blincyto for certain blood cancers, and Lumakras for specific cancers.

Founded in 1980, Amgen is headquartered in Thousand Oaks, California.

This instant news alert was generated by narrative science technology and financial data from MarketBeat in order to provide readers with the fastest reporting and unbiased coverage. Please send any questions or comments about this story to contact@marketbeat.com.