gocatamig (MK-6070)

P1/2, N=170, Recruiting, Merck Sharp & Dohme LLC | Not yet recruiting --> Recruiting

This study systematically characterized three clinical-stage CD3×DLL3 BsAbs, Tarlatamab (AMG757), BI764532 and HPN328, via structural modeling, T-cell activation assays, cytokine profiling, and tumor cytotoxicity tests. BI764532 demonstrated a balanceed efficacy (ORR 18% in SCLC), while Tarlatamab achieved an ORR range of 13-40% across clinical trials. IS distance and epitope binding are strongly correlated with efficacy and safety of DLL3-targeted BsAbs, providing a critical framework for optimizing T-cell engager design in cancer immunotherapy.

P1/2, N=242, Recruiting, Merck Sharp & Dohme LLC | Trial completion date: Aug 2029 --> Feb 2030

P1/2, N=232, Active, not recruiting, Harpoon Therapeutics, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA) | Recruiting --> Active, not recruiting

P1/2, N=170, Not yet recruiting, Merck Sharp & Dohme LLC

MK-6070 also demonstrates antitumor activity in mixed tumors, affecting DLL3-negative prostate cancer cells after engagement with surrounding DLL3-expressing tumor cells, supporting a potential bystander effect. Overall, these data demonstrate the promising activity of MK-6070 in NEPC preclinical models including heterogeneous tumors, supporting the clinical development of MK-6070.

MK-6070 also demonstrates anti-tumor activity in mixed tumors, impacting DLL3-negative prostate cancer cells after engagement with surrounding DLL3-expressing tumor cells, supporting a potential bystander effect. Overall, these data demonstrate promising activity of MK-6070 in NEPC preclinical models including heterogeneous tumors, supporting the clinical development of MK-6070.

P1/2, N=242, Recruiting, Merck Sharp & Dohme LLC | N=138 --> 242

The 2024 FDA approval of tarlatamab-a bispecific T-cell engager (BiTE) targeting DLL3 and CD3-marks a pivotal advancement, demonstrating improvement in survival in refractory disease. This review examines three key advances reshaping SCLC management: (1) mechanistic links between DLL3-driven tumorigenesis and PD-L1-mediated immunosuppression, (2) clinical progress in antibody-drug conjugates (ADCs) with next-generation payloads (e.g., FZ-AD005), multispecific BiTEs (e.g., HPN328), and engineered CAR-T/NK cells with enhanced metabolic resilience, and (3) precision strategies combining liquid biopsy for dynamic DLL3 profiling with immuno-PET imaging using [89Zr]Zr-DFO-SC16. Emerging synergies, such as combining DLL3-targeted BiTEs with ICIs to amplify T-cell infiltration or reprogramming CAR-T mitochondrial metabolism, further underscore the potential of multimodal approaches. Together, these developments signal a transformative era in SCLC treatment, where molecular diagnostics and engineered immunotherapies converge to address unmet clinical needs.

P1/2, N=138, Recruiting, Merck Sharp & Dohme LLC | Trial completion date: Oct 2028 --> Aug 2029 | Trial primary completion date: Oct 2028 --> Aug 2029

P1/2, N=232, Recruiting, Harpoon Therapeutics, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA) | Trial completion date: Jun 2027 --> Nov 2027 | Trial primary completion date: Jun 2027 --> Nov 2027

P1/2, N=138, Recruiting, Merck Sharp & Dohme LLC | Not yet recruiting --> Recruiting