Tarlatamab Demonstrates Favorable and Manageable Safety Profile in Small Cell Lung Cancer
Key Clinical Takeaways
- Design/Population: In the phase 3 DeLLphi-304 trial 496 patients with relapsed small cell lung cancer were randomized to tarlatamab, a DLL3-targeting bispecific T-cell engager (n = 252), or standard chemotherapy (topotecan, lurbinectedin, or amrubicin; n = 244). The primary end point was safety.
- Key Outcomes: Hematologic toxicities were markedly lower with tarlatamab vs chemotherapy (anemia 2% vs 27.9%; neutropenia 4.4% vs 22.1%). Grade ≥3 treatment-related adverse events occurred in 17% during month 1, decreasing over time, compared with >38% for chemotherapy. Cytokine release syndrome occurred in 56% (mostly low-grade), and neurologic events in 45%, including dysgeusia (23%) and low-grade immune effector cell-associated neurotoxicity (6%)
- Clinical Relevance: Tarlatamab maintained a predictable, manageable safety profile with lower hematologic toxicity than chemotherapy, supporting its tolerability as a second-line therapy for relapsed SCLC.
Safety analyses from the phase 3 DeLLphi-304 trial show that tarlatamab, a bispecific T-cell engager targeting DLL3, maintained a predictable and manageable safety profile among previously treated patients with small cell lung cancer (SCLC).
These results were presented by Martin Schuler, MD, University Hospital Essen, Germany, at the 2025 European Society for Medical Oncology (ESMO) Congress in Berlin, Germany.
In this study, 496 patients with relapsed SCLC were randomized to receive either tarlatamab (n = 252) or standard chemotherapy with topotecan, lurbinectedin, or amrubicin (n = 244). Patients treated with tarlatamab underwent either 48-hour (n = 209) or 6-to-8-hour (n = 43) monitoring. The primary end point was safety.
At analysis, hematologic and infection treatment-related adverse events included anemia (2% of patients in the tarlatamab arm vs 27.9% of patients in the chemotherapy arm), neutropenia (4.4% vs 22.1%, respectively), thrombocytopenia (0.4% vs 11.8%, respectively), and infection (1.2% vs 8.6%, respectively).
Grade ≥3 tarlatamab treatment-related adverse events, occurred in 17% of patients during the first month, 9% between months 1 to 3, and 12% thereafter, while rates of chemotherapy treatment-related adverse events consistently exceeded 38%. The most frequently reported treatment-related adverse event was cytokine release syndrome, occurring in 56% of patients with rates that were consistent across all subgroups (performance status, presence of liver or brain metastases, prior PD-L1 inhibitor use, and tumor burden). Any grade cytokine release syndrome led to hospitalization on cycle 1 days 1 or 8 in 7.7% of patients in the 48-hour arm and 7% of patients in the 6-to-8-hour arm.
Neurologic treatment-related adverse events occurred in 45% of patients and most frequently included dysgeusia (23%), which appeared after a median of 28 days and lasted a median of 126 days among resolved cases, with no instances requiring treatment discontinuation. Immune effector cell-associated neurotoxicity syndrome was reported in 6% of patients (predominantly grades 1 or 2) and was associated with cytokine release syndrome in 93% of patients.
As Dr Schuler et al concluded, “tarlatamab demonstrated a predictable and manageable safety profile in [second-line] SCLC, with no new safety signals identified.”
Source:
Schuler M, Mountzios G, Cho BC, et al. Detailed safety analysis of DeLLphi-304: The first phase III study to evaluate tarlatamab versus chemotherapy for previously treated small cell lung cancer. Presented at the 2025 ESMO Congress. October 17-21, 2025; Berlin, Germany. LBA100
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