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

P1/2, N=36, Not yet recruiting, Alx Oncology Holdings Inc.

Nanoprodrugs orchestrate a sophisticated cascade of immune activation through four synergistic mechanisms: 1) size-switchable disassembly upon glutathione/ cholesterol exposure for deep tumor penetration; 2) redox imbalance driven by reactive nitrogen species accumulation and glutathione depletion via the synergistic action of oxaliplatin, ferrocene, and RRx-001 for ferroptosis augmentation; 3) immunogenic cell death induction via ferroptosis-apoptosis to initiate tumor immunity cycle, promoting T cell infiltration; and 4) T cell function reinvigoration with the downregulation of programmed cell death protein 1 and T-cell immunoglobulin 3 expression through cholesterol depletion in TME. This integrated approach achieved primary and distant tumor growth suppression, established durable immune memory against recurrence, and systemically enhanced the antitumor immunity. By concurrently targeting tumor immunogenicity, TME immunosuppression, and T cell exhaustion, this multidimensional strategy represents a transformative advancement in cancer immunotherapy.

In conclusion, this study systematically characterizes the clinical and immunological associations of CD47 across multiple cancers and highlights its potential role in pancreatic adenocarcinoma, supporting the further investigation of CD47 as a therapeutic target.

DSP216 with an 'active' (DSP216a), but not with an 'inactive' Fc (DSP216i), triggered CD16-signaling in a reporter cell line, and the combination of checkpoint blockade and ADCC by DSP216a potentiated NK-mediated cytotoxicity. These encouraging findings support the continued preclinical evaluation of DSP216.

P1, N=50, Recruiting, FBD Biologics Limited | Trial completion date: Aug 2026 --> May 2027 | Trial primary completion date: Aug 2026 --> Dec 2026

P1/2, N=500, Active, not recruiting, FBD Biologics Limited | Recruiting --> Active, not recruiting | N=150 --> 500

P1, N=80, Recruiting, FBD Biologics Limited | N=60 --> 80

This challenge was underscored by a pivotal setback in the field: the Phase III trial of Magrolimab, the first anti-CD47 therapy to reach this stage, which failed to meet its primary endpoint and ultimately led to the discontinuation of its development program...Furthermore, we summarize the major clinical challenges, including safety concerns, resistance mechanisms, and diagnostic complexities. By synthesizing these key findings, this review provides valuable insights for optimizing future drug design, refining combination regimens, and guiding patient selection strategies, thereby offering a crucial reference for overcoming current limitations and fully realizing the therapeutic potential of this promising axis.