Dr Marron on the Evolving Role of Tarlatamab in SCLC

“Tarlatamab is currently our preferred second-line therapy [in extensive-stage small cell lung cancer]. Most patients receive induction chemoimmunotherapy followed by immunotherapy maintenance, but the majority ultimately experience recurrence. We [have observed] not only amazing response rates but [also notable] durability of response [with tarlatamab]."

Thomas Marron, MD, PhD, director of the Early Phase Trials Unit at the Tisch Cancer Institute and a tenured professor of medicine at Mount Sinai, discussed how emerging data from the phase 1b DeLLphi-303 trial (NCT05361395) have informed the evolving role of tarlatamab (Imdelltra) in the treatment paradigm for extensive-stage small cell lung cancer (SCLC).

DeLLphi-303 evaluated tarlatamab, a DLL3-directed bispecific T-cell engager, in combination with frontline chemoimmunotherapy or in the maintenance setting following induction therapy. Initial data readouts during the International Association for the Study of Lung Cancer 2025 World Conference on Lung Cancer demonstrated that adding tarlatamab to maintenance durvalumab (Imfinzi) or atezolizumab (Tecentriq) improved survival vs maintenance anti–PD-L1 therapy alone, with a median OS of 25.3 months (n = 88; 95% CI, 20.3-not evaluable). The disease control rate (DCR) was 60%, which exceeded historical expectations for extensive-stage SCLC, according to Marron.

Updated results from the frontline chemoimmunotherapy cohort shared at the 2025 ESMO Congress demonstrated an ORR of 71% (95% CI, 61%-80%), with a complete response rate of 5% and a partial response rate of 66%, with the regimen at a median follow-up of 13.8 months (95% CI, 12.5-15.0).

Based on these findings, tarlatamab has become the preferred second-line therapy for patients who progress after induction chemoimmunotherapy and maintenance immunotherapy. Marron emphasized that tarlatamab not only induces meaningful response rates but also demonstrates durable benefit, contributing to a survival “tail” that suggests a subset of patients may achieve long-term disease control.

However, he noted that the current data have not yet been compared with standard-of-care therapy in randomized trials and that the relative contribution of individual components within combination regimens have yet to be fully understood.

Ongoing and future studies informed by DeLLphi-303 will therefore be critical to confirm the optimal role for tarlatamab in both the front and second lines in SCLC, Marron explained. Mature findings will help clarify sequencing strategies, define the populations most likely to benefit, and guide where the SCLC treatment paradigm should advance next, he concluded.