P2/3, N=43, Terminated, CytoDyn, Inc. | Active, not recruiting --> Terminated; FDA required the sponsor to halt enrollment in the trial and transition participants to available therapies for the treatment of their disease. The trial was subsequently terminated once participants were transitioned.

P2/3, N=56, Terminated, CytoDyn, Inc. | Active, not recruiting --> Terminated; FDA required the sponsor to halt enrollment in the trial and transition participants to available therapies for the treatment of their disease. The trial was subsequently terminated once participants were transitioned.

Our findings identify the CCL5/CCR5 axis as a key mediator of tumor-stromal crosstalk driving cisplatin resistance in NEPC. Mechanistically, CAF-derived CCL5 activates AKT signaling in tumor cells by promoting the formation of the CCR5/β-arrestin1/p85 complex. Targeting this pathway with maraviroc in combination with cisplatin offers a promising therapeutic strategy for overcoming drug resistance in NEPC.

P1/2, N=332, Completed, Bristol-Myers Squibb | Phase classification: P1b/2 --> P1/2

P2, N=20, Terminated, CytoDyn, Inc. | Active, not recruiting --> Terminated; FDA required the sponsor to halt enrollment in the trial and transition participants to available therapies for the treatment of their disease. The trial was subsequently terminated once participants were transitioned.

P1/2, N=46, Completed, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial completion date: Sep 2024 --> Feb 2025 | Trial primary completion date: Sep 2024 --> Feb 2025

Translational techniques employing CCR5 antagonists such as Maraviroc, GAG-binding modulators, glycoengineered CCL5 variants, delivery systems, and their integration with immune checkpoint inhibitors (ICIs) and targeted therapies are highlighted for their considerable therapeutic promise. Critical research priorities, encompassing single-cell phenotyping, CRISPR-mediated screening of chemokine pathways, and structural-functional mapping, are outlined to facilitate precise modulation of the CCL5/CCR5 axis in targeted cancer therapy. This review addresses structural biology and tumor immunology to identify the CCL5/CCR5 axis as a multifaceted yet promising biological target for innovative cancer therapeutics.

Therapeutic targeting of CCL4-CCR5 signaling with maraviroc, an FDA-approved antiviral drug, significantly reduced brain metastasis progression without exerting direct cytotoxic effects on tumor cells. These findings highlight a promising therapeutic strategy that focuses on modulating glial communication within the tumor microenvironment. By disrupting the supportive glial niche rather than targeting tumor cells directly, this represents a distinct and potentially less toxic approach for managing brain metastases.

P2/3, N=6, Completed, CytoDyn, Inc. | Active, not recruiting --> Completed | N=25 --> 6

P1/2, N=10, Terminated, CytoDyn, Inc. | N=48 --> 10 | Active, not recruiting --> Terminated; Study terminated prematurely due to business reasons. Participants are no longer examined or receiving intervention.

P2, N=484, Completed, CytoDyn, Inc. | Active, not recruiting --> Completed | Phase classification: P2b --> P2

P2, N=70, Not yet recruiting, Federal University of São Paulo | Phase classification: P=N/A --> P2