Future Directions With Tarlatamab in Small Cell Lung Cancer

Watch the first part of the interview with Dr Paulson.

Clinical data from the phase 1b DeLLphi-303 study investigating tarlatamab (Imdelltra) plus anti–PD-L1 agnets atezolizumab (Tecentriq) or durvalumab (Imfinzi) in extensive-stage small cell lung cancer (ES-SCLC) were presented at the IASLC 2025 World Conference on Lung Cancer. In the cohort presented by Kelly Paulson, MD, the combination therapy was used as a first-line maintenance treatment for patients whose cancer hadn't progressed after initial chemotherapy. The treatment showed an unprecedented overall survival rate, with patients living a median of 25.3 months after starting the regimen. The therapy was found to have an acceptable safety profile. The most common adverse effect was cytokine release syndrome, which was mild in most cases and decreased over time.

These results suggest that combining tarlatamab with anti–PD-L1 therapy could be a promising new strategy for treating ES-SCLC, and the larger phase 3 DeLLphi-305 is now underway to further evaluate this approach.

Paulson notes that while the findings of DeLLphi-303 were encouraging, unanswered questions persist. First, a randomized controlled trial is needed to confirm the findings. Therefore, there is great anticipation for the results of the phase 3 DeLLphi-305 trial.

Second, DeLLphi-303 raised questions about the optimal timing for administering tarlatamab. While the current trial evaluated it as a maintenance therapy, future presentations of the DeLLphi-303 trial will provide data on starting tarlatamab earlier—specifically, with the second cycle of chemoimmunotherapy—to see if this results in even better outcomes.

Finally, Paulson wonders whether combination immunotherapy should be used in the relapsed/refractory setting. While tarlatamab is currently approved as a monotherapy in this setting, the new data demonstrate that it can be safely given in combination with other immunotherapies for maintenance, which suggests a need to explore this combined approach for patients with relapsed disease.

Read the full interview with Dr Paulson.