155TiP Phase II study of tarlatamab, a half-life extended bispecific T-cell engager (HLE BiTE®) immuno-oncology therapy targeting DLL3, in third-line or later small cell lung cancer (SCLC)

Abstract

SCLC is an aggressive cancer with a high response rate to platinum-based first-line chemotherapy. Disease recurrence is common in limited-stage and inevitable in extensive-stage becoming progressively resistant to subsequent therapies. There is no approved third-line therapy. The Notch ligand, delta-like ligand 3 (DLL3), is a promising target because it is highly expressed on the cell membrane in SCLC and minimally so in normal tissue. Tarlatamab is a DLL3-targeting HLE BiTE® immuno-oncology therapy designed to bind DLL3 on target cancer cells and CD3 on T cells, forming a cytolytic synapse and resulting in T cell activation/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 (objective response rate [ORR]: 20%) with an acceptable safety profile. These findings support further study of tarlatamab in SCLC in this area of unmet clinical need. 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 following 1 platinum-based regimen (including a PD-L1 inhibitor, if standard of care, with certain exceptions per protocol) and at least 1 other line of therapy, treated brain metastases, and ECOG performance status ≤1. The primary endpoint for the primary analysis is ORR per RECIST 1.1 as assessed by blinded independent central review (BICR). 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. Enrollment has begun. NCT05060016. Medical writing support for this poster was provided by Eugene Gillespie, PhD, of Amgen, Inc. Amgen Inc.