In vivo, RRx-001 significantly inhibits tumor growth, enhances T-cell infiltration, promotes M1 macrophage polarization, downregulates PD-L1 expression, and strengthens anti-tumor immunity through T cell-related pathways. With both metabolic and immunomodulatory effects, RRx-001 provides a basis for novel HCC therapies, and future research could explore its synergistic effects with immune checkpoint inhibitors.

Although the sample size is small, these findings support the clinical benefit of zanidatamab treatment for HER2-positive SGC.

P1/2, N=47, Active, not recruiting, M.D. Anderson Cancer Center | Trial primary completion date: Mar 2026 --> Mar 2028 | Trial completion date: Mar 2026 --> Mar 2028

P1, N=106, Terminated, Shattuck Labs, Inc. | Completed --> Terminated; Development discontinued

P1/2, N=80, Recruiting, ALX Oncology Inc. | Not yet recruiting --> Recruiting

P2, N=120, Active, not recruiting, Akeso | Recruiting --> Active, not recruiting | Trial completion date: Dec 2026 --> Jun 2027 | Trial primary completion date: Jul 2025 --> Dec 2026

P1, N=128, Recruiting, D3 Bio (Wuxi) Co., Ltd | Trial completion date: Mar 2026 --> Dec 2028 | Trial primary completion date: Mar 2026 --> Dec 2028

P1/2, N=154, Active, not recruiting, Akeso | Recruiting --> Active, not recruiting | N=114 --> 154 | Trial completion date: Feb 2024 --> Jun 2027 | Trial primary completion date: Feb 2023 --> Dec 2026

P3, N=999, Recruiting, Akeso | Not yet recruiting --> Recruiting

P1/2, N=154, Completed, Akeso | N=250 --> 154 | Trial completion date: Jun 2026 --> Dec 2025 | Trial primary completion date: May 2025 --> Nov 2025 | Active, not recruiting --> Completed

Despite the clinical success of anti-CD20 monoclonal antibodies (mAbs) such as rituximab in the treatment of B-cell lymphoma, therapeutic resistance and relapse remain significant challenges, particularly in tumors with low or heterogeneous CD20 expression resulting from antigen loss or phenotypic shifts. In vivo, CO-005 triggered robust intratumoral PCCD and remodelled the tumor microenvironment, characterized by increased macrophage and neutrophil infiltration, thereby enhancing innate immune activation and supporting a dual-mechanism mode of action that couples direct cancer cell killing with myeloid engagement. These findings position CO-005 as a mechanistically distinct and immunologically active therapeutic with the potential to overcome limitations of both CD20- and CD47-directed therapies and expand treatment options for B-cell lymphoma.

P2/3, N=310, Not yet recruiting, Groupe Oncologie Radiotherapie Tete Cou