Imdelltra Improves Survival For Some With Small Cell Lung Cancer

Among patients with small cell lung cancer (SCLC), treatment with Imdelltra (tarlatamab-dlle) was found to improve overall survival (OS) when compared with chemotherapy, regardless of chemotherapy-free interviews (CFIs) or prior administration of anti-PD-(L)1 therapy, trial results have shown.

Data from the phase 3 DeLLphi-304 trial were presented at the European Society for Medical Oncology 2025 Congress in Berlin.

The median OS was 10.9 months in the Imdelltra arm versus 6.4 months in the chemotherapy arm among patients with a CFI of less than 90 days. The 12-month OS rates in this population were 40% versuus 24% with Imdelltra and chemotherapy, respectively.

Among patients with a CFI of 90 days or longer, the median OS was 17.1 months compared with 10.6 months in each arm, with respective 12-month OS rates of 64% and 48. Regarding patients with disease progression within two weeks of their most recent platinum-containing treatment, the Kaplan-Meier estimated six-month OS rates were 55% with Imdelltra and 35% with chemotherapy.

Among patients with prior receipt of anti–PD-(L)1 agents, the median OS was 14.1 months in the Imdelltra arm and 8.3 months in the chemotherapy arm; the respective 12-month OS rates were 53% versus 36%. In the group of patients without prior anti–PD-(L)1 therapy, the median OS was 13.6 months versus 8.3 months, and the 12-month OS rates were 53% versus 40%. Overall, data showed that prior exposure to anti–PD-(L)1 agents did not affect OS benefits with Imdelltra vs chemotherapy.

“In the second line, standard chemotherapies have demonstrated modest survival benefits, especially [in] those patients with platinum-resistant disease, [who] often have a poor prognosis. 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,” presenting author 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.”

In the randomized DeLLphi-304 trial, 509 patients were assigned to receive Imdelltra (254 patients) or investigator’s choice of chemotherapy (255 patients), which included options of topotecan (185 patients), lurbinectedin (47 patients) and amrubicin (23 patients). Investigators stratified patients by prior receipt of anti–PD-(L)1 agents, CFI interval, presence of brain metastases and intended chemotherapy.

In the Imdelltra and chemotherapy arms, respectively, 43% and 45% of patients had a CFI of less than 90 days, and 57% and 55% had a CFI of 90 days or longer. Additionally, 71% of patients in both arms had prior receipt of anti–PD-(L)1 therapy, while 29% from both arms did not. Investigators noted that subgroup baseline characteristics appeared to be balanced between treatment arms.

Across the different CFI and anti–PD-(L)1 subgroups, rates of grade 3 (severe) or higher treatment-related side effects ranged from 24% to 30% in the Imdelltra arm and 58% to 69% in the chemotherapy arm. Any-grade events of cytokine release syndrome (CRS) occurred in 51% to 59% of patients who received Imdelltra across various subgroups, and subgroup status did not impact the risk of CRS.

The FDA granted accelerated approval toImdelltra as a treatment for patients with extensive-stage SCLC following progression on prior platinum-based chemotherapy in May 2024. Supporting data for this indication came from the phase 2 DELLphi-301 trial.

References

1. “Tarlatamab as second-line (2L) treatment for small cell lung cancer (SCLC): Outcomes by chemotherapy-free interval (CFI) and prior PD-(L)1 inhibitor use in the phase 3 DeLLphi-304 trial” by Dr. Pedro F. Simoes da Rocha et al., presented at the European Society for Medical Oncology (ESMO) Congress 2025; October 17-21, 2025; Berlin, Germany. LBA101.
2. “FDA grants accelerated approval to tarlatamab-dlle for extensive stage small cell lung cancer,” news release. https://tinyurl.com/48k34rw5