Moving beyond immune checkpoint inhibitors (ICI), targeting DLL3 with tarlatamab in previously treated ES-SCLC generated an unprecedented response...Due to tumor heterogeneity and plasticity, rational combinations pursuing broader cancer cell vulnerabilities are likely necessary in the future to prevent relapse. Better tools for response monitoring are urgently needed to gauge progress.

Early monitoring and prompt supportive management during initial treatment cycles are essential. These findings broaden current knowledge of tarlatamab safety in real-world practice and support prospective studies to pharmacovigilance-based signal stratification and monitoring strategies.

P1, N=9, Recruiting, Cancer Institute and Hospital, Chinese Academy of Medical Sciences | Not yet recruiting --> Recruiting

P1, N=69, Active, not recruiting, Boehringer Ingelheim | Trial completion date: Jul 2027 --> Apr 2027

P1, N=55, Active, not recruiting, Boehringer Ingelheim | Trial completion date: Apr 2027 --> Dec 2027 | Trial primary completion date: Feb 2027 --> Oct 2027

Tarlatamab, a representative agent in this class, has been approved for clinical use, and multiple TCE agents are currently under clinical development. Although DLL3-TCE shows promising prospects in the clinical management of SCLC, as a novel therapeutic modality, many clinicians still lack an in-depth understanding of their mechanisms of action, appropriate patient populations, and clinical management. To standardize the clinical application of DLL3-TCE in China, the Small Cell Lung Cancer Expert Committee of the Chinese Society of Clinical Oncology convened a consensus panel to develop the Chinese Expert Consensus on Delta-like Ligand 3-T Cell Engager Therapy for SCLC based on evidence-based medicine and expert practical experience, with the aim of providing standardized guidance for the clinical use of DLL3-TCE agents..

In a predominantly Hispanic, heavily pre-treated real-world population with high CNS disease burden, Tarlatamab demonstrated feasible administration, manageable immune-mediated toxicity, and clinically meaningful antitumor activity.

Consequently, to date, only one classical TCE developed for solid tumors - tarlatamab - has been granted a marketing approval...Furthermore, HER2×CD2 induced markedly lower cytokine release than a HER2×CD28 bispecific while mediating comparable improvement in anti-tumor cytotoxicity. These findings establish our novel CD2-targeted costimulatory bispecific antibody approach as a promising and potentially safe way to expand and enhance TCE immunotherapy for solid tumors.

P3, N=430, Not yet recruiting, PrECOG, LLC.

P1, N=55, Active, not recruiting, Boehringer Ingelheim | Recruiting --> Active, not recruiting

P1, N=150, Recruiting, Innovent Biologics (Suzhou) Co. Ltd. | Not yet recruiting --> Recruiting

From approval of immune checkpoint inhibitors and lurbinectedin, a newer chemotherapy agent, to novel immunotherapies such as tarlatamab, a DLL3-CD3 bispecific T-cell engager, and other upcoming promising drugs, the therapeutic armamentarium for SCLC is steadily expanding. In this study, we review the current landscape of both systemic therapy as well as radiation therapy for SCLC, with a focus on major developments over the past decade, current standards of care, and novel therapeutics that are expected to revolutionize the treatment of this aggressive malignancy.