Subcutaneous Tarlatamab Matches IV Exposure With Low-Grade Toxicity in Phase 1b ES-SCLC Trial
核心洞察
Phase 1b DeLLphi-308 found 15 mg subcutaneous tarlatamab achieved serum exposures comparable to the approved 10 mg intravenous dose given every two weeks in ES-SCLC.
Cytokine-release syndrome (搜索) was predominantly grade 1 or 2, with no grade 3 or higher events and no dose interruptions or discontinuations required.
The 15 mg subcutaneous dose produced a preliminary objective response rate of 30%, versus 20% in the 10 mg group.
Subcutaneous administration of tarlatamab was well tolerated and produced preliminary antitumor activity in patients with previously treated extensive-stage small cell lung cancer (搜索) (ES-SCLC), according to phase 1b DeLLphi-308 findings presented at the International Association for the Study of Lung Cancer (IASLC) 2026 World Conference on Lung Cancer (WCLC; Abstract MO15.07).
The trial is the first investigation of subcutaneous delivery of the approved bispecific T-cell engager (搜索) (BiTE®) immunotherapy, an approach intended to lower adverse events and offer patients a more convenient option than intravenous administration. Delayed, lower peak serum concentrations with subcutaneous dosing could potentially affect the incidence or severity of adverse events such as cytokine-release syndrome (搜索) (CRS).
"The findings from DeLLphi-308 suggest that [the] 15-mg subcutaneous tarlatamab dose can achieve serum exposures comparable to the approved 10-mg intravenous dosing administered every 2 weeks while maintaining a favorable safety profile," said lead study author Pedro Rocha, MD, of Hospital Universitari Vall d'Hebron in Barcelona, Spain. "The predominantly low-grade cytokine-release syndrome (搜索) events and preliminary antitumor activity support continued investigation of this more convenient route of administration."
Trial Design and Dosing
The open-label, multicenter trial enrolled patients with ES-SCLC whose disease had progressed or recurred after at least one platinum-based therapy. It consisted of two parts.
In part 1, subcutaneous tarlatamab was administered with a step-up dose of 1 mg on day 1, followed by target doses of either 10 mg or 15 mg on days 8 and 15 and every two weeks thereafter. Patients were monitored 24 hours after dose administration on days 1 and 8. In part 2, patients received the selected 15 mg subcutaneous dose every two weeks, and post-dose monitoring was reduced to one to two hours and later eliminated.
The primary endpoint was safety and tolerability of the subcutaneous treatment, with secondary endpoints including pharmacokinetics, immunogenicity, and preliminary efficacy.
Pharmacokinetics and Exposure
A total of 20 patients received subcutaneous tarlatamab at 10 mg and 40 received the 15 mg dose. Subcutaneous administration at 10 mg demonstrated about 75% bioavailability relative to the intravenous dose, while the 15 mg subcutaneous dose demonstrated comparable exposure to the approved intravenous dose. The 15 mg dose was selected as the target dose for part 2.
Safety Findings
As of the March 5, 2026, data cutoff, treatment-related adverse events occurred in 85% of patients in the 15 mg group, with 10% experiencing a grade 3 or higher treatment-related adverse event.
The most common all-grade treatment-related adverse events were dysgeusia (50% with 10 mg and 45% with 15 mg), CRS (35% and 38%, respectively), decreased appetite (35% and 20%), and injection-site reactions (35% and 50%). Two grade 4 events were reported — lymphopenia (搜索) and pleural effusion (搜索) — both in the 10 mg group. No grade 5 events were reported.
CRS was mostly grade 1 (25% in the 10 mg group and 28% in the 15 mg group) or grade 2 (10% in each group). No grade 3 or higher CRS events occurred, and no events required dose interruption or discontinuation. Immune effector cell–associated neurotoxicity syndrome was reported in 15% of patients in the 10 mg group and 3% of the 15 mg group, all grade 1 events.
Preliminary Efficacy
The preliminary objective response rate was 20% in the 10 mg group and 30% in the 15 mg group.
Investigators concluded that subcutaneous tarlatamab was well tolerated and that the observed safety profile, pharmacokinetic findings, and preliminary antitumor activity, together with the potential convenience of subcutaneous administration, support further investigation. Updated data from the latest data cutoff were scheduled to be shared in an oral presentation on September 15.