Phase 2 study highlights flexible dosing options for tarlatamab in relapsed SCLC

Extended-interval dosing regimens of tarlatamab demonstrated efficacy, safety and pharmacokinetic profiles generally consistent with the established every-two-week regimen in patients with previously treated for small cell lung cancer (SCLC), according to results from the randomized Phase 2 DeLLphi-309 study presented at the International Association for the Study of Lung Cancer (IASLC) 2026 World Conference on Lung Cancer (WCLC).

Tarlatamab administered at 10 mg every two weeks has previously demonstrated superior overall survival compared with chemotherapy in patients with previously treated SCLC. DeLLphi-309 evaluated whether less frequent dosing of 20 mg every three weeks or 30 mg every four weeks could maintain comparable clinical activity while offering greater treatment flexibility.

These data suggest that the tarlatamab 20 mg every-three-week and 30 mg every-four-week regimens may offer treatment flexibility for patients with SCLC and that alternative dosing schedules for bispecific T-cell engagers may achieve outcomes consistent with an established regimen."

Jonathan Goldman, M.D., University of California Los Angeles

Adults whose SCLC progressed or recurred after first-line platinum-based chemotherapy were randomized to intravenous tarlatamab 10 mg every two weeks, 20 mg every three weeks, or 30 mg every four weeks after a 1 mg step dose. The primary endpoint was confirmed objective response rate by blinded independent central review. No formal statistical hypotheses were prespecified, and the results were presented descriptively.

As of May 7, 2026, 252 patients had been randomized. BICR-confirmed objective response rates were 40% with 10 mg every two weeks, 31% with 20 mg every three weeks and 27% with 30 mg every four weeks. Investigator-assessed response rates were 36%, 37% and 31%, respectively. Median progression-free survival by blinded independent central review was 4.2, 4.1 and 2.7 months, respectively.

Six-month overall survival rates were 72% with the every-two-week regimen, 85% with the every-three-week regimen and 69% with the every-four-week regimen. Median overall survival was not yet estimable after approximately nine months of median follow-up across the three regimens.

Treatment-emergent and treatment-related adverse event rates were similar across regimens, without evidence of new or unexpected safety signals. Incidence of any-grade treatment-related adverse events of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) were numerically higher in the extended-interval dosing regimens. CRS occurred in 60% to 70% of patients and was predominantly grade 1 or 2. ICANS was observed in 6% to 12% of patients. Steady-state trough concentrations were comparable across the three dosing schedules.