DLL3-Targeted Bispecific T-Cell Engager Therapy in Relapsed or Refractory Small-Cell Lung Cancer: A Mini Systematic Review of the DeLLphi Clinical Trials
DOI:
https://doi.org/10.55136/apsj513Keywords:
Tarlatamab, Bispecific T-Cell Engager Therapy, BiTE Therapy, Small-Cell Lung Cancer , Relapsed Small-Cell Lung Cancer, Refractory Small-Cell Lung Cancer, Oncology , Immunotherapy , Targeted Therapy , Cancer Pharmacotherapy, Precision Oncology , Cytokine Release SyndromeAbstract
Background: Small-cell lung cancer (SCLC) is associated with poor prognosis following relapse. Delta-like ligand 3 (DLL3)-tar-
geted bispecific T-cell engagers (BiTEs) such as tarlatamab represent a promising therapeutic innovation.
Aim: To systematically evaluate the efficacy, safety, and clinical relevance of the DLL3-targeted bispecific T-cell engager tarlat-
amab in adults with relapsed or refractory SCLC.
Data Sources: A systematic search of Ovid MEDLINE (2018-October 2025) and manual searching of Google Scholar and ref-
erence lists identified clinical studies evaluating tarlatamab in adult SCLC.
Study Selection: Prospective full-text phase 1-3 clinical trials evaluating tarlatamab in adults with relapsed or refractory
small-cell lung cancer and reporting efficacy and/or safety outcomes were included Risk of bias was assessed using ROBINS-I
(non-randomised) and RoB 2 (Randomised Controlled Trials).
Results: Three studies (n = 836) were included. DeLLphi-300 (Phase 1) reported an objective response rate (ORR) of 23.4%,
median overall survival (mOS) of 13.2 months, and manageable cytokine-release syndrome (CRS). DeLLphi-301 (Phase 2) con-
firmed efficacy at 10 mg Q2W (ORR 40%, mOS 14.3 months). DeLLphi-304 (Phase 3) demonstrated superior survival compared
with chemotherapy (13.6 vs 8.3 months, HR, 0.60) and fewer grade ≥3 adverse events.
Conclusion: Tarlatamab demonstrates consistent, durable responses and survival benefits with manageable toxicity, supporting
further investigation of DLL3-targeted BiTE therapy as a promising treatment option for relapsed/refractory SCLC. Further
trials should define long-term safety, optimal sequencing, and biomarker-guided use.
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