DeLLphi-309: Extended-Interval Tarlatamab Dosing Shows Comparable Activity in Relapsed SCLC
核心洞察
Phase II DeLLphi-309 found that tarlatamab given every 3 or 4 weeks produced efficacy and safety consistent with the approved every-2-week regimen in relapsed small cell lung cancer (搜索).
BICR-confirmed objective response rates were 40% with 10 mg every 2 weeks, 31% with 20 mg every 3 weeks, and 27% with 30 mg every 4 weeks.
Six-month overall survival reached 85% in the 20-mg every-3-week arm versus 72% and 69% in the every-2-week and every-4-week arms, with median OS not yet estimable.
Extended-interval dosing of intravenous tarlatamab at 20 mg every 3 weeks or 30 mg every 4 weeks produced efficacy and safety consistent with the approved tarlatamab regimen in patients with small cell lung cancer (搜索) (SCLC), according to results from the randomized 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 (搜索).
Tarlatamab administered at 10 mg every 2 weeks has previously demonstrated superior overall survival compared with chemotherapy in patients with previously treated SCLC. DeLLphi-309 evaluated whether less frequent dosing could maintain comparable clinical activity while offering greater treatment flexibility.
Study Design and Population
The phase II study enrolled adults whose SCLC had progressed on or recurred after first-line platinum-based therapy. Patients were randomly assigned to receive intravenous tarlatamab at 10 mg every 2 weeks (n = 83), 20 mg every 3 weeks (n = 84), or 30 mg every 4 weeks (n = 85), all following a 1-mg step dose.
The primary endpoint was confirmed objective response rate by blinded independent central review (BICR). No formal statistical hypotheses were prespecified, and results were presented descriptively. As of May 7, 2026, 252 patients had been randomized.
Response and Survival Outcomes
BICR-confirmed objective response rates were 40% (95% confidence interval [CI] = 29%–51%) in the standard 10-mg every-2-weeks arm, 31% (95% CI = 21%–42%) with 20 mg every 3 weeks, and 27% (95% CI = 18%–38%) with 30 mg every 4 weeks. Investigator-assessed objective response rates were 36%, 37%, and 31% in the 10-mg, 20-mg, and 30-mg groups, respectively.
Median duration of response was 8.3 months in the control arm and 5.6 months in the 20-mg every-3-weeks arm; median duration of response was not estimable in the 30-mg every-4-weeks arm despite longer follow-up.
By BICR, 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, overall survival rates were 72%, 85%, and 69% for the 10-mg, 20-mg, and 30-mg groups, respectively. Median overall survival was not yet estimable in the investigational arms after approximately nine months of median follow-up, compared with 11.2 months in the standard dosing arm.
Safety and Pharmacokinetics
Treatment-emergent and treatment-related adverse event rates were similar across treatment arms, including rates of grade 3 or higher events, with no evidence of new or unexpected safety signals. Treatment-emergent adverse events leading to treatment discontinuation were reported in one patient in the standard dosing arm, six patients in the 20-mg every-3-weeks arm, and 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 (CRS) occurred in 60.2% of patients in the standard dosing arm, 70.2% in the 20-mg every-3-weeks arm, and 64.7% in the 30-mg every-4-weeks arm, with most cases grade 1 or 2. Any-grade immune effector cell–associated neurotoxicity syndrome (ICANS) was reported in 6% to 12% of patients across the three groups. Incidence of any-grade treatment-related CRS and ICANS was numerically higher in the extended-interval dosing regimens.
Steady-state geometric mean Ctrough values were comparable across the three treatment arms, supporting the pharmacokinetic consistency of the alternative schedules.