Tarlatamab for patients (pts) with previously treated small cell lung cancer (SCLC): Primary analysis of the phase II DeLLphi-301 study

Tarlatamab, a bispecific T-cell engager (BiTE), represents a new immunotherapeutic approach for SCLC. It binds to both delta-like ligand 3 (DLL3) on SCLC cells and CD3 on T cells, resulting in T-cell mediated tumor lysis. A phase 1 study demonstrated encouraging safety and efficacy (median duration of response (mDoR): 12.3 mo; median overall survival (mOS): 13.2 mo) in previously treated SCLC. Here, the phase 2 data from the DeLLphi-301 study are presented. Pts with SCLC who relapsed after 1 platinum-based regimen (± checkpoint inhibitor) and at least 1 other prior line of therapy received 10 mg or 100 mg tarlatamab Q2W. The primary endpoint was objective response rate (ORR) by blinded independent central review (RECIST 1.1). Other endpoints were DoR, progression-free survival (PFS), OS, and treatment-emergent adverse events (TEAEs). Overall, 220 pts received tarlatamab. The median follow-up was 10.6 mo for efficacy outcomes (Table). At the 10 mg dose, ORR was 40.0%, mPFS was 4.9 mo, mOS was 14.3 mo, and mDoR was not reached, with 57.5% of responders experiencing ≥ 6 mo of response and 55.0% still with an ongoing response. The most common TEAE was cytokine release syndrome (CRS; 51.1%, 10 mg; 60.9%, 100 mg), primarily occurring in cycle 1, and was mostly grade 1 or 2. Incidence of grade 3 CRS (0.8%, 10 mg; 5.7%, 100 mg) and grade 3 immune effector cell-associated neurotoxicity syndrome (ICANS) and associated neurologic events was low (0%, 10 mg; 4.6%, 100 mg), with no grade 4 or 5 events. Discontinuations due to treatment-related AEs were infrequent (3.0%, 10 mg; 3.4%, 100 mg). Similar safety profiles were seen with 24h or 48h inpatient monitoring.Table: LBA9210 mg (n = 100)*100 mg (n = 88)*ORR, % (97.5% CI)40.0 (29.1–51.7)31.8 (21.1–44.1) Complete response, n (%)1 (1.0)7 (8.0) Partial response, n (%)39 (39.0)21 (23.9) Stable disease, n (%)30 (30.0)27 (30.7) Progressive disease, n (%)20 (20.0)13 (14.8) Not evaluable, n (%)2 (2.0)4 (4.5) Death before post-baseline scan, n (%)6 (6.0)13 (14.8) No post-baseline scan, n (%)2 (2.0)3 (3.4)mDoR, mo (95% CI)NE (5.9–NE)NE (6.6–NE)Disease control rate % (95% CI)70.0 (60.0, 78.8)62.5 (51.5, 72.6)mOS, mo (95% CI)14.3 (10.8–NE)NE (12.4–NE)mPFS, mo (95% CI)4.9 (2.9–6.7)3.9 (2.6–4.4)*Efficacy analysis set per intention-to-treat (ITT) analysis (Pts in safety substudy (n = 34) not included as data immature). NE = not estimable Open table in a new tab *Efficacy analysis set per intention-to-treat (ITT) analysis (Pts in safety substudy (n = 34) not included as data immature). NE = not estimable Tarlatamab demonstrated impressive antitumor activity with durable responses and promising survival. Tarlatamab showed a favorable benefit-risk profile with no new safety signals, supporting the use of tarlatamab in pts with previously treated SCLC.