Phase 2 study of tarlatamab, a DLL3-targeting, half life-extended, bispecific T-cell engager (HLE BiTE) immuno-oncology therapy, in relapsed/refractory small cell lung cancer (SCLC).

TPS8603 Background: SCLC is characterized by rapid growth and early development of metastases. Platinum-based first-line chemotherapy is associated with a high initial response rate; however, disease recurrence is common. Delta-like ligand 3 (DLL3) is a Notch ligand that is upregulated and aberrantly expressed on the cell surface in most SCLC, making it a compelling therapeutic target. Tarlatamab is an HLE BiTE immuno-oncology therapy designed to bind DLL3 on target cancer cells and CD3 on T cells, forming a cytolytic synapse inducing T cell activation and expansion and T cell-dependent killing of tumor cells. Interim results of an ongoing first-in-human study in patients with relapsed/refractory SCLC (NCT03319940) show preliminary evidence for tarlatamab efficacy in pretreated patients with confirmed partial responses in 20% of patients and duration of response of 8.7 months (Owonikoko TK, et al. Abstract 8510. Presented at: ASCO Annual Meeting, June 4–8, 2021; Virtual). Grade ≥ 3 treatment-related AEs (TRAEs) occurred in 27% of patients and TRAEs resulted in discontinuation in 5% of patients. This promising efficacy/safety profile supports further study of tarlatamab in SCLC. Methods: NCT05060016 is a phase 2, open-label study evaluating tarlatamab in patients with relapsed/refractory SCLC after two or more lines of prior treatment. Part 1 is a dose characterization phase in which subjects will be randomized 1:1 to two active doses of tarlatamab. Part 2 will continue enrollment for the selected target dose only based on interim analysis of Part 1. Key eligibility criteria include adults with histologically or cytologically confirmed SCLC whose disease progressed/recurred after two or more lines of prior treatment including at least 1 platinum-based regimen (including a PD-L1 inhibitor, if standard of care, with certain exceptions per protocol), treated brain metastases, ECOG performance status ≤1, and life expectancy ≥ 12 weeks in the opinion of the investigator. The primary endpoint for the primary analysis is ORR per RECIST 1.1 as assessed by blinded independent central review. Secondary objectives are to evaluate antitumor activity by additional measures (duration of response, progression-free survival, disease control rate and duration, overall survival), safety and tolerability, immunogenicity, and pharmacokinetics. Sites in North America, Asia and Europe are participating in the trial with subjects already enrolled and enrollment ongoing. Clinical trial information: NCT05060016.