Extended-interval dosing of intravenous tarlatamab, at 20 mg every 3 weeks or 30 mg every 4 weeks, demonstrated efficacy and safety that was consistent with the approved tarlatamab dosing regimen in patients with small cell lung cancer (SCLC), according to findings from the phase II DeLLphi-309 study presented at the International Association for the Study of Lung Cancer (IASLC) 2026 World Conference on Lung Cancer (WCLC; Abstract OA05.01).
“These data suggest that the tarlatamab 20-mg every-3-week and 30-mg every-4-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,” said presenting author Jonathan Goldman, MD, of the University of California Los Angeles.
Study Methods
The phase II study enrolled patients with SCLC that had progressed on or recurred after first-line platinum-based therapy. Patients were randomly assigned to receive intravenous tarlatamab at either 10 mg every 2 weeks (n = 83), 20 mg every 3 weeks (n = 84), or 30 mg every 4 weeks (n = 85), all after a 1-mg step dose.
The primary endpoint was confirmed objective response rate, by blinded independent central review.
Key Findings
The objective response rate by blinded independent central review was 40% (95% confidence interval [CI] = 29%–51%) in the standard dosing arm, 31% (95% CI = 21%–42%) in the 20-mg arm, and 27% (95% CI = 18%–38%) in the 30-mg arm. The median duration of response was 8.3 months in the control arm and 5.6 months in the 20-mg arm; the median duration of response was not estimable in the 30-mg arm, despite longer follow-up.
The investigator-assessed objective response rates were 36%, 37%, and 31% in the 10-mg, 20-mg, and 30-mg groups, respectively.
By blinded independent central review, the median progression-free survival was 4.2 months with the standard dosing regimen, 4.1 months with 20 mg every 3 weeks, and 2.7 months with 30 mg every 4 weeks. At 6 months, the overall survival rates were 72%, 85%, and 69% for the 10-mg, 20-mg, and 30-mg groups, respectively. The median overall survival was not yet estimable in the investigational arms, compared with 11.2 months in the standard dosing arm.
Treatment-emergent and treatment-related adverse events rates were similar across treatment arms. Grade 3 or higher treatment-emergent and treatment-related adverse events rates were also similar. Treatment-emergent adverse events leading to treatment discontinuation were reported in one patient in the standard dosing arm, in six patients in the 20-mg every-3-weeks arm, and in five patients in the 30-mg every-4-weeks arm; fatal events were reported in 3.6%, 1.2%, and 7.1% of patients in the 10-mg, 20-mg, and 30-mg arms, respectively.
Treatment-related cytokine-release syndrome occurred in 60.2% of patients in the standard dosing arm, in 70.2% in the 20-mg every-3-weeks arm, and in 64.7% of patients in the 30-mg every-4-weeks arm. Most cases of cytokine-release syndrome were grade 1 or 2. Any-grade immune effector cell–associated neurotoxicity syndrome was reported in 6% to 12% of patients across the three groups.
Steady-state geometric mean Ctrough were comparable across the three treatment arms.
DISCLOSURES: For full disclosures of the study authors, visit abstractsonline.com.
