KEY TAKEAWAYS
- The phase 1 DeLLphi-303 trial aimed to investigate the efficacy and safety of tarlatamab plus PD-L1 inhibitor as 1LM in patients with ES-SCLC.
- The primary endpoints were to determine DLTs, TEAEs, TRAEs.
- Researchers noticed that tarlatamab plus a PD-L1 inhibitor showed promising safety and efficacy; further investigation is ongoing.
Current first-line maintenance (1LM) therapies for extensive-stage small cell lung cancer (ES-SCLC) offer limited benefit, highlighting the need for innovative treatments to enhance patient outcomes. Tarlatamab, a bispecific T-cell engager (BiTE®) immunotherapy, targets delta-like ligand 3 (DLL3)-positive cancer cells, showing durable responses and significant survival benefits in previously treated patients with SCLC.
Sally Lau and the team aimed to assess the safety and efficacy of tarlatamab plus a PD-L1 inhibitor as 1LM therapy in patients with ES-SCLC, following prior chemo-immunotherapy.
They performed an inclusive analysis of patients with ES-SCLC who had not progressed after completing 4-6 cycles of first-line (1L) platinum-etoposide with a PD-L1 inhibitor, when available. Within 8 weeks of finishing the last cycle of chemo-immunotherapy, patients received tarlatamab (10 mg IV every 2 weeks) in combination with either atezolizumab (1680 mg IV every 4 weeks) or durvalumab (1500 mg IV every 4 weeks) until disease progression.
The study’s primary endpoints included dose-limiting toxicities (DLTs) and treatment-emergent and treatment-related adverse events (TEAEs, TRAEs). Secondary endpoints assessed progression-free survival (PFS), overall survival (OS), and disease control rate (DCR).
About 88 patients (male: 62.5%, median age: 64.0 years; number of prior 1L platinum-etoposide cycles: 4, 86.4%; 5, 5.7%; 6, 8.0%) received tarlatamab with atezolizumab or durvalumab. The median follow-up was 10.0 months (range: 1.4-20.4). No DLTs were observed. The most common all-grade treatment-emergent adverse events (TEAEs) were cytokine release syndrome (CRS; 53.4%), dysgeusia (47.7%), and fatigue (34.1%).
The most common grade ≥ 3 TEAEs were hyponatremia (10.2%), neutropenia (6.8%), and anemia (6.8%). CRS predominantly occurred in cycle 1 and was mainly grade 1-2; grade 3 CRS occurred in 1 patient. Immune effector cell-associated neurotoxicity syndrome and associated neurological events occurred in 11.4%/2.3%/0% (any grade/grade 3/grade 4) of patients.
The median time from initiation of 1L chemo-immunotherapy to the start of 1LM was 3.6 months (range: 2.9-5.8). From the start of 1LM, the median PFS was 5.6 months (95% CI: 3.6-9.0), and the median OS was immature due to insufficient follow-up time; the Kaplan-Meier estimate for OS at 9 months was 88.9%. The DCR was 62.5% (95% CI: 51.5-72.6), with a median duration of disease control of 9.3 months (95% CI: 5.6-not estimable).
The study concluded that tarlatamab in combination with a PD-L1 inhibitor as 1LM therapy for ES-SCLC demonstrated a manageable safety profile, durable disease control, and notable survival outcomes. No new or unexpected toxicities were identified, supporting the continuation of tarlatamab’s investigation in the ongoing phase 3 DeLLphi-305 randomized controlled study (NCT06211036).
The trial was sponsored by the Amgen.
Source: https://cattendee.abstractsonline.com/meeting/20598/presentation/3222
Clinical Trials: https://clinicaltrials.gov/study/NCT05361395
https://clinicaltrials.gov/study/NCT06211036
Lau S, Ahn M.J, Moskovitz M, et al. (2024). “Tarlatamab with a PD-L1 Inhibitor as First-Line Maintenance after Chemo-immunotherapy for ES-SCLC: DeLLphi-303 Phase 1b Study.” Presented at IASLC-WCLC 2024, September 8, 2024; Singapore.
