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214TiP Tarlatamab after chemoradiotherapy in limited-stage small cell lung cancer (LS-SCLC): DeLLphi-306 (NCT06117774)

Year: 2024

Type: article

Abstract: SCLC is an aggressive disease with poor survival. Despite initial response to chemoradiation, most patients with LS-SCLC relapse. Between 85-96% of patients with SCLC have tumor expression of Delta-like ligand 3 (DLL3), a Notch ligand aberrantly expressed on the surface of SCLC cells with minimal expression in healthy cells, making DLL3 an attractive therapeutic target. In the phase II DeLLphi-301 study, tarlatamab, a bispecific T cell engager (BiTE®) immunotherapy targeting DLL3 and T cell co-receptor CD3, demonstrated antitumor activity and a manageable safety profile in patients with previously treated extensive stage-SCLC: 40% objective response and a 6-month overall survival (OS) rate (KM estimate) of 73% at 10 mg Q2W (NEJM 2023;389:2063). DeLLphi-306 is a randomized (1:1), double-blind, placebo-controlled Phase 3 trial examining tarlatamab (10 mg Q2W in 28-day cycles) clinical activity and safety in ≈ 400 patients with LS-SCLC following concurrent chemoradiation. Key patient inclusion criteria include age ≥ 18 years, histologically/cytologically confirmed LS-SCLC, completion of platinum-based chemotherapy with concurrent radiotherapy without progression, ECOG PS ≤ 1, chemoradiotherapy-attributed toxicities resolved to grade ≤ 1 excluding alopecia, and life expectancy ≥ 12 weeks. Key exclusion criteria include transformed NSCLC; interstitial lung disease; active pneumonitis; non-concurrent chemotherapy and thoracic radiotherapy during chemoradiation; prior DLL3 pathway-selective inhibitor therapy; and history of severe/life-threatening events from immune-mediated therapy. Primary endpoint is progression-free survival (PFS) per blinded independent central review (RECIST 1.1) with OS as a key secondary endpoint. Additional secondary endpoints include investigator-assessed PFS, objective response, disease control, duration of response, time to progression, pharmacokinetics, tarlatamab immunogenicity, and safety/tolerability. NCT06117774. Medical writing support was provided by William W Stark, Jr, PhD, Amgen Inc. Amgen. Amgen.

Source: ESMO Open

DOI: 10.1016/j.esmoop.2024.102787