Subcutaneous administration of tarlatamab was well tolerated in patients with extensive-stage small cell lung cancer (ES-SCLC) in the phase IB DeLLphi-308 trial. Investigators were able to eliminate the preplanned post-dose monitoring in the second part of the study due to the safety of the subcutaneous dose, according to findings presented at the International Association for the Study of Lung Cancer (IASLC) 2026 World Conference on Lung Cancer (WCLC; Abstract MO15.07).
“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 events and preliminary antitumor activity support continued investigation of this more convenient route of administration.”
Background and Study Methods
The DeLLphi-308 trial represents the first investigation of a subcutaneous administration of the approved bispecific T-cell engager tarlatamab in patients with SCLC to lower adverse events and provide a more convenient option for patients.
The open-label multicenter trial, which consisted of two parts, enrolled patients with ES-SCLC whose disease had progressed or recurred after at least one platinum-based therapy. In part 1, subcutaneous tarlatamab was administered with a step-up dose of 1 mg on day 1, followed by the target doses of either 10 mg or 15 mg on days 8, 15, and every 2 weeks thereafter. Patients were monitored 24 hours post dose administration on days 1 and 8. In part 2, patients received the selected dose of 15-mg subcutaneous tarlatamab every 2 weeks and post-dose monitoring was able to be reduced to 1 to 2 hours and later eliminated.
The primary endpoint was the safety and tolerability of the subcutaneous treatment. Secondary endpoints including pharmacokinetics, immunogenicity, and preliminary efficacy.
Key Findings
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 vs the intravenous dose, while the 15-mg subcutaneous dose demonstrated comparable exposure to the approved intravenous dose.
The most common all-grade treatment-related adverse events were dysgeusia (50% with 10 mg and 45% with 15 mg), cytokine-release syndrome (35% and 38%, respectively), decreased appetite (35% and 20%), and injection-site reactions (35% and 50%). Two grade 4 events were reported, including lymphopenia and pleural effusion, both in the 10-mg group. No grade 5 events were reported.
Cytokine-release syndrome was mostly grade 1 (25% in 10-mg group and 28% in 15-mg group) or grade 2 (10% in each group). No grade 3 or higher events of cytokine- release syndrome were reported, 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 in 3% of the 15-mg group, all grade 1 events.
The preliminary objective response rate was 20% in the 10-mg group and 30% in the 15-mg group.
DISCLOSURES: For full disclosures of the study authors, visit abstractsonline.com.
