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.

P3, N=198, Not yet recruiting, ImmuneOnco Biopharmaceuticals (Shanghai) Inc.

P2, N=90, Recruiting, Kahr Bio Australia Pty Ltd | Not yet recruiting --> Recruiting

In this study, we propose a Gas-Metal Synergy Strategy, which integrates immune activation and biosafety, by engineering a pH-responsive manganese-based zeolitic imidazolate framework (named MRPH) nanoplatform co-loaded with the nitric oxide (NO) donor RRX-001...Both in vitro and in vivo studies demonstrate that MRPH significantly enhances gas-amplified metalloimmunotherapy. This work pioneers a low-toxicity paradigm that integrates gas therapy and metal-based immunotherapy, offering a transformative approach to solid tumor immunotherapy.

Investigational agents targeting CD47, such as magrolimab, aim to induce phagocytosis of tumor cells by TAMs...Compared to relatively low CD47 expression in primary CRC tumors, CRC liver metastases had very high CD47 expression. Quantification of TAM signatures and CD47 expression represent key biomarkers to monitor in patient samples during exploration of CD47-blockade agents in the clinic.

P1, N=20, Terminated, Chia Tai Tianqing Pharmaceutical Group Nanjing Shunxin Pharmaceutical Co., Ltd. | N=43 --> 20 | Trial completion date: Feb 2026 --> Jun 2025 | Recruiting --> Terminated | Trial primary completion date: Oct 2025 --> Jun 2025; This study was closed due to business reasons. Closure was not prompted by any safety or efficacy concerns.

P3, N=780, Not yet recruiting, Groupe Oncologie Radiotherapie Tete et Cou

P1, N=86, Completed, Bio-Thera Solutions | Recruiting --> Completed | N=42 --> 86

P2, N=90, Not yet recruiting, Kahr Bio Australia Pty Ltd

CD47-targeted combinations demonstrate encouraging early phase efficacy and manageable safety in hematologic malignancies, with signals of benefit in higher-risk MDS, TP53-mutant AML, relapsed/refractory DLBCL, and rituximab-refractory iNHL. However, recent Phase III trials in newly diagnosed AML Daver et al. [27], and Zeidner et al. [26] did not confirm this benefit, underscoring that CD47 blockade remains investigational and requires validation in rigorously designed randomized studies.

Hu5F9-G4 demonstrates potential as a therapeutic agent in CRC by promoting M2d-to-M1 macrophage polarization, suppressing tumor progression, and influencing the autophagy pathway. These findings highlight CDKN1A and MAP1LC3B as promising targets for CRC therapy.

P1, N=25, Terminated, Kahr Medical | N=36 --> 25 | Trial completion date: Jun 2025 --> Oct 2025 | Active, not recruiting --> Terminated; Slow enrolment