FDA Approves Imdelltra for Extensive-Stage Small Cell Lung Cancer

The Food and Drug Administration (FDA) granted traditional approval to Imdelltra (tarlatamab-dlle) for adult patients with extensive-stage small cell lung cancer (ES-SCLC) with disease progression on or after platinum-based chemotherapy.

Efficacy was studied in the DeLLphi-304 trial, which took place at multiple centers and included patients with small cell lung cancer whose disease had grown after earlier treatment with platinum-based chemotherapy, with or without an anti–PD-(L)1 immunotherapy.

Median overall survival was 13.6 months for patients who received Imdelltra and 8.3 months for those who received standard chemotherapy. Median progression-free survival was 4.2 months in the Imdelltra group and 3.2 months in the standard chemotherapy group. The trial also showed an improvement in shortness of breath at week 18 for patients who received Imdelltra.

In addition, data from the phase 3 DeLLphi-304 trial were presented at the European Society for Medical Oncology (ESMO) 2025 Congress in Berlin, Germany.

“DeLLphi-304 is the first randomized phase 3 trial to demonstrate superior OS with [Imdelltra] compared with standard chemotherapy. Importantly, this survival benefit extended to patients with platinum-resistant disease,” Dr. Pedro F. Simoes da Rocha, of Vall d’Hebron University Hospital and Vall d’Hebron Institute of Oncology in Barcelona, Spain, stated in the presentation. “These findings reinforce the use of [Imdelltra] as a standard of care in second-line SCLC, including those patients with worse prognosis, such as [those] with platinum-resistant disease.”

The studies end goals included overall survival, along with key secondary measures such as progression-free survival, which reflects how long patients lived without their cancer growing. Doctors assessed this using standard RECIST guidelines, and the study also included select patient-reported outcomes.

In DeLLphi-304, 509 patients were randomly assigned in a 1-to-1 ratio to receive either Imdelltra or the doctor’s choice of standard chemotherapy, which could be topotecan, lurbinectedin or amrubicin. Patients stayed on treatment until their cancer grew again or the side effects became too hard to manage.

The recommended dose of Imdelltra is 1 milligram (mg) on the first day of the first treatment cycle, followed by 10 mg on days 8 and 15, and then every two weeks after that. Treatment continues until the cancer grows again or the side effects become too difficult to manage.

The prescribing information for Imdelltra includes a boxed warning because it can cause life-threatening or fatal cytokine release syndrome and neurologic side effects, including a condition called immune effector cell-associated neurotoxicity syndrome. It also carries warnings about low blood counts, infections, liver problems, allergic reactions and risks to an unborn baby.

This review was conducted through Project Orbis, a program from the FDA Oncology Center of Excellence that allows several countries to review cancer treatments at the same time. For this review, the FDA worked with regulatory agencies in Australia, Canada and the United Kingdom. Reviews of the application are still ongoing in those countries.

The FDA also used the Real-Time Oncology Review program, which allowed the agency to evaluate data earlier than usual, along with the Assessment Aid, a voluntary tool that helps organize information for review. The FDA approved this application one month before its planned decision date.

This application received priority review, and Imdelltra was granted breakthrough designation. These designations are part of the FDA’s efforts to speed the development and review of treatments for serious conditions.

Priority review is a faster FDA review process for treatments that may offer meaningful improvements for serious conditions, while breakthrough designation is granted to treatments that show early signs of substantial benefit and allows for more guidance and quicker development.

References

1. “FDA grants traditional approval to tarlatamab-dlle for extensive stage small cell lung cancer,” by U.S. FDA. News; Nov. 19, 2025.
2. “Imdelltra Improves Survival For Some With Small Cell Lung Cancer.” CURE; Oct. 18, 2025.

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