195MO Tarlatamab in previously treated small cell lung cancer (SCLC): DeLLphi-300 phase I study long-term outcomes and intracranial activity

Tarlatamab, a bispecific T cell engager (BiTE®) immunotherapy targeting delta-like ligand 3 (DLL3), showed durable antitumor activity and manageable safety in previously treated SCLC. Here we report long-term outcomes and intracranial activity from the DeLLphi-300 phase I study. Tarlatamab was evaluated in patients (pts) with previously treated SCLC. Pts with treated, stable brain metastases were eligible. Primary endpoint was safety. Secondary endpoints included objective response rate (ORR) per mRECIST 1.1 by investigator, duration of response (DOR), progression-free survival (PFS), and overall survival (OS). In retrospective exploratory analyses, CNS tumor sum of diameters (SOD) was assessed per mRANO-BM by BICR in pts with ≥ 1 brain lesion at baseline. This report, with data cutoff (DCO) 14.5 months (mos) beyond Paz-Ares, J Clin Oncol 2023, includes fully enrolled cohorts of pts treated with clinically relevant doses (≥ 10 mg) of tarlatamab. 152 pts were treated with tarlatamab ≥ 10 mg (follow-up range 0.2–34.3 mos; median 12.1 mos). Across cohorts, ORR was 25.0% with mDOR of 11.2 mos (table). 25 pts had treatment duration ≥ 52 weeks (range 52–150), including 8 pts treated ≥ 104 weeks. mPFS and mOS were 3.5 mos and 17.5 mos, respectively, with PFS and OS estimates at 12 mos of 16.7% and 57.9%. Of 16 pts with a baseline CNS lesion ≥ 10 mm, CNS tumor SOD decreased ≥ 30% in 10 pts (62.5%). Of 8 pts who completed brain radiotherapy (RT) ≥ 50 days before tarlatamab initiation, 3 pts (37.5%) had ≥ 30% decrease in CNS tumor SOD. No new safety signals were identified. Table: 195MOORRmDORmPFSmOS% (95% CI)mos (95% CI)Tarlatamab (N = 152)a25.0 (18.3, 32.7)11.2 (6.6, 22.3)3.5 (2.7, 3.8)17.5 (11.4, NE)10 mg (n = 17)b35.3 (14.2, 61.7)14.9 (3.0, NE)4.0 (1.6, 11.0)20.3 (5.1, NE)30 mg (n = 8)b12.5 (0.3, 52.7)3.8 (NE, NE)1.8 (1.1, NE)7.2 (1.5, NE)100 mg (n = 76)b19.7 (11.5, 30.5)22.3 (5.6, NE)3.7 (1.9, 4.5)17.5 (11.7, NE)100 mg (eIV) (n = 32)c37.5 (21.1, 56.3)6.5 (3.5, 11.2)3.8 (1.7, 5.7)12.6 (7.9, NE)Other (n = 19)d21.1 (6.1, 45.6)NE (6.8, NE)2.8 (2.1, 3.5)NE (6.0, NE)aDCO 2 Oct 2023 b1-step dosing: 1 mg (Day 1); target dose: Days 8, 15, then Q2W cCohorts: 30 mg eIV → 100 mg Q2W; 100 mg eIV → 100 mg Q2W dCohorts: 1 → 25 → 100 mg Q2W; 1 → 100 → 200 mg Q3W; 1 → 100 mg D1/D8 eIV, extended IV; NE, not estimable Open table in a new tab aDCO 2 Oct 2023 b1-step dosing: 1 mg (Day 1); target dose: Days 8, 15, then Q2W cCohorts: 30 mg eIV → 100 mg Q2W; 100 mg eIV → 100 mg Q2W dCohorts: 1 → 25 → 100 mg Q2W; 1 → 100 → 200 mg Q3W; 1 → 100 mg D1/D8 eIV, extended IV; NE, not estimable In longer follow-up of DeLLphi-300, tarlatamab demonstrated durable responses and unprecedented survival outcomes in previously treated SCLC. While limited to analyses of treated, stable brain metastases, CNS tumor shrinkage following tarlatamab therapy and long after RT supports further study of intracranial efficacy of tarlatamab.