Tarlatamab is a delta-like ligand 3 (DLL3)-targeted bispecific T-cell engager (BiTe) currently approved in the second-line setting for treating patients with small cell lung cancer (SCLC).
Per the standard approved schedule, a 10-mg dose of tarlatamab is administered as a one-hour intravenous infusion once every two weeks. To improve treatment convenience and reduce treatment burden without compromising efficacy and safety, several clinical trials are exploring extended-interval dosing regimens of tarlatamab, including the phase 1b DeLLphi-303 and the ongoing phase III DeLLphi-312 studies.
Additionally, during the 2026 World Conference on Lung Cancer, Jonathan Goldman, MD, presented findings from the phase II DeLLphi-309 trial comparing extended-interval dosing regimens to the approved dosing schedule for tarlatamab as second-line treatment in patients with SCLC.
From Discovery to Practice in SCLC: Redefining Standards of Care and the Next Generation of Targeted Therapies
Tarlatamab Extended-Interval Dosing Regimens in Patients With SCLC
Registered WCLC 2026 attendees can watch this session with on-demand access to WCLC recordings via the virtual platform. WATCH NOW
“Extended-interval tarlatamab dosing regimens may improve patient flexibility as well as allow co-treatment with other agents, such as chemo-immunotherapy,” said Dr. Goldman, Professor of Medicine at the University of California, Los Angeles.
In DeLLphi-309, 252 patients with SCLC whose disease had progressed on or recurred after frontline treatment with platinum-based chemotherapy were randomly assigned in a 1:1:1 ratio to receive either 10 mg tarlatamab once every two weeks (10 mg Q2W), 20 mg tarlatamab once every three weeks (20 mg Q3W), or 30 mg tarlatamab once every four weeks (30 mg Q4W).
Notably, outpatient administration of tarlatamab was allowed for all dosing regimens.
Dr. Goldman noted imbalances in prognostic factors across groups. More patients in the 30 mg Q4W arm had an Eastern Cooperative Oncology Group (ECOG) performance status of 1, liver metastases at baseline, and higher disease burden, as indicated by a higher sum of target lesion diameters.
Pharmacokinetic analyses demonstrated comparable geometric mean steady-state troughs for tarlatamab, indicating similar treatment exposures across the three dosing schedules.
The primary endpoint, objective response rate (ORR) by Blinded Independent Committee Review (BICR), was comparable across dosing regimens. The ORRs were 39.8%, 31%, and 27.1% in the 10 mg Q2W, 20 mg Q3W, and 30 mg Q4W cohorts.
The responses were durable, with a median duration of response of 8.3 months, 5.6 months, and not estimable in the 10 mg Q2W, 20 mg Q3W, and 30 mg Q4W arms, respectively. Dr. Goldman said a higher proportion of patients in the 30 mg Q4W group ended treatment before their first post-baseline imaging assessment.
Median progression-free survival (PFS) was 4.2, 4.1, and 2.7 months in the 10 mg Q2W, 20 mg Q3W, and 30 mg Q4W arms, with corresponding 6-month PFS point estimates of 34%, 31%, and 24%.
Dr. Goldman said overall survival (OS) was favorable across the three regimens.
With a median follow-up of nine months, the median OS was 11.2 months in the 10 mg Q2W arm, and not estimable in the 20 mg Q3W and 30 mg Q4W arms, with corresponding 6-month OS point estimates of 85%, 72%, and 69%, respectively.
The overall safety profile was comparable across arms, with similar rates of treatment-emergent adverse events (TEAEs), ≥ grade 3 adverse events (AEs), and AEs leading to treatment interruptions. The rates of serious AEs and AEs leading to discontinuation were numerically higher in the extended-interval dosing arms, compared to the currently approved tarlatamab dosing.
Dr. Goldman said that while the incidence of treatment-related cytokine release syndrome was higher with extended-interval tarlatamab dosing, a majority were of grade 1 or 2. Treatment-related immune effector cell-associated neurotoxicity syndrome (ICANS) events were higher in the 30 mg Q4W arm, 11.8% versus 6% in the other two arms.
“The extended-interval [tarlatamab] dosing regimens provided durable objective responses and maintained the OS seen with the approved dosing schedule,” Dr. Goldman said. “Although there were some increases in specific AEs, the overall safety profiles were similar and comparable across the dosing regimens, and manageable.”
