DeLLphi-303 trial

In this video, Prof Mariana Brandao, medical oncologist at the Institut Jules Bordet in Brussels, and Prof Sebahat Ocak, thoracic oncologist at the CHU UCL in Namur, discuss the results of one of the most anticipated studies presented during WCLC 2025: DeLLphi-303.

DeLLphi-303 is a phase 1b study in which the bispecific T-cell engager tarlatamab is evaluated as add-on therapy in the maintenance treatment of patients with extensive-stage small-cell lung cancer (ES-SCLC).

ES-SCLC patients were eligible for this study if they had completed 4 to 6 cycles of first line platinum-etoposide chemotherapy plus an anti-PD-L1 agent (if available). Within 8 weeks from the start of the last chemo-immunotherapy cycle, patients without disease progression received tarlatamab (10 mg IV Q2W) with either atezolizumab (1680 mg IV Q4W) or  durvalumab (1500 mg IV Q4W) as first line maintenance therapy until disease progression. 

The study included a total of 88 patients with a median age of 64 years. The overall survival (OS) data presented in this study were impressive, with a median of 25.3 months and a 1-year OS rate of 82%. Furthermore, tarlatamab + anti-PD-L1 maintenance induced a response in 24% of patients, with a disease control rate of 60%. For Prof Ocak, this high response rate is especially striking given the fact that these patients already received 4-6 cycles of chemotherapy. The disease control obtained with this strategy was also durable, with 36% of patients having a sustained disease control for more than a year.

In terms of toxicity, the DeLLphi-303 study did not reveal any new safety signals relative to previous studies with this agent. No dose limiting toxicities were encountered, nor did the study reveal any treatment-related fatalities. Overall, the incidence of adverse events leading to discontinuation of tarlatamab was low at only 6%. In their discussion of the safety data, Prof Ocak and Prof Brandao underscored that most adverse events occurred during the first 3 months of the treatment, after which their incidence dropped. The incidence of cytokine release syndrome (56%) and ICANS (6%) was in line with previous reports, and these adverse events rarely exceeded grade 1 or 2 in severity.

In conclusion, the addition of tarlatamab to anti-PD-L1 as first line maintenance therapy for ES-SCLC demonstrates a manageable safety profile, sustained disease control, and an unprecedented overall survival. As such, these findings identify tarlatamab as a very promising agent in this setting and spur the enthusiasm for ongoing phase III studies evaluating this agent in patients with ES-SCLC (e.g., DeLLphi-305, DeLLphi-312).