Tarlatamab in Small Cell Lung Cancer and Extrapulmonary Small Cell Carcinoma: A Single-Centre Retrospective Cohort Study of Routine-Practice Outcomes
Ayrton Bangolo, Lili Zhang, Jiahe Zhao, Behzad Amoozgar, Sarvarinder Gill, Shibhani Rajanna, Shareif Abdelwahab, Andres Molina, Tanner Robinson, Umangpreet Gill, Andrea Torres, Akhil Akula, Mahe Tahniyat, Maamoun Seklawi, Tri Vo, Thilini Suriyaarachchi, Oriana Castillo-Briceno, Sujeewa Kalubowila, Tori Salorenzo, Darya Klechykava, Avery Kellman, Kaushik Roy, Victor H. Villarreal, Alia Ramzan, Hamza Haq, Rajendra Gunti, Soroush Abaresh, Gurmanjot Kaur, Jonathan Montalvo, Zhongxuan-Jonathan Wang, Aanya Srivastava, Lipi Gudiboina, Benjamin S. Feuer, Vennela Talla, Rajin Persaud, Winnie Noe, Shalini Subramanian, Simcha Weissman, Martin Gutierrez, Miguel Gonzalez-VelezBackground: Tarlatamab, a Delta-like ligand 3 (DLL3)-targeting bispecific T-cell engager (BiTE), has demonstrated significant efficacy in relapsed small cell lung cancer (SCLC) in clinical trials. However, real-world clinical outcomes and its efficacy in extrapulmonary small cell carcinoma (EPSCC) remain sparsely characterized. Methods: We conducted a retrospective, single-institution cohort study of 24 adult patients with moderately pretreated advanced SCLC (n = 19) or EPSCC (n = 5) who received standard-of-care tarlatamab. Endpoints included objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and safety. Results: Patients had received a median of two prior lines of therapy, and 38% had baseline brain metastases. The overall intent-to-treat (ITT) ORR was 25.0%. Among response-evaluable patients (n = 18), the ORR was 33.3%. Efficacy was notably discordant between histologies: the SCLC cohort achieved an ITT ORR of 31.6% (46.2% in evaluable patients), whereas 100% of EPSCC patients experienced progressive disease. Systemic responses were observed in patients with baseline brain metastases (ORR 33.3%). The safety profile was manageable; any-grade CRS and ICANS occurred in 58% and 29% of patients, respectively. Severe (Grade ≥ 3) toxicities were rare, and tocilizumab was utilized therapeutically in 50% of patients for low-grade toxicity. Conclusions: These real-world data are consistent with tarlatamab’s systemic efficacy and tolerability in SCLC. The lack of clinical benefit observed in this small EPSCC cohort raises a hypothesis that requires prospective biomarker-correlated evaluation.