Table 4 Overview of compounds inhibiting the CXCL12-CXCR4/ACKR3 interaction in recent in vivo experiments and in completed or ongoing clinical trials
Agent name (company) | Mechanism of action | Targeting diseases | In vivo model/Clinical trials | Results | Ref. |
|---|---|---|---|---|---|
Plerixafor/AMD3100/Mozobil (Genzyme) | CXCR4 antagonist | Cervical cancer | Cervical cancer xenografts | Plerixafor with radiochemotherapy blunted therapy-induced increases in CXCL12 signaling & reduced tumor growth and intestinal toxicity | [266] |
Breast cancer | Triple negative breast cancer murine model | Liposomal-AMD3100 with immunotherapy reduced tumor size & prolonged survival | [267] | ||
Ovarian cancer | Ovarian cancer murine model | Plerixafor with immunotherapy inhibited tumor growth & prolonged survival by preventing multifaceted immunosuppression | [268] | ||
Multiple myeloma | NCT00903968 (Phase I/II: completed) | Plerixafor in combination with bortezomib is safe & the objective response rate is high | [326] | ||
NCT05087212 (Phase IV: recruiting) | Â | Â | |||
Chronic lymphocytic leukemia | NCT00694590 (Phase I: completed) | Plerixafor is well-tolerated, supporting further studies | [272] | ||
Myelodysplastic syndromes | NCT01065129 (Phase I: completed) | Plerixafor with azacytidine chemotherapy is safe & demonstrated encouraging response rates | [273] | ||
Pediatric cancer | NCT01288573 (Phase I/II completed) | Plerixafor with standard G-CSF ± chemotherapy for HSC mobilization was well tolerated & efficacious | [274] | ||
Metastatic pancreatic cancer | NCT04177810 (Phase II: recruiting) | Â | Â | ||
Glioblastoma | NCT03746080 (Phase II: recruiting) | Â | Â | ||
WHIM syndrome | NCT00967785 (Phase I/II: recruiting) | Â | Â | ||
COVID-19 | NCT05411575 (Phase II: ongoing) | Â | Â | ||
NCT04646603 (Phase II: recruiting) | Â | Â | |||
Fanconi anemia | NCT02678533 (Phase I/II: completed) | HSC mobilization with plerixafor is safe & more efficient in younger patients without bone marrow failure | [284] | ||
NCT02931071 (Phase II: completed) | HSC mobilization with plerixafor is safe & efficient in pediatric patients | [285] | |||
Sickle cell disease | NCT03226691 (Phase I: completed) | Safe & sufficient collection of HSCs in most but not all participants. HSC mobilization is impacted by age, bone marrow reserve & disease severity | [286] | ||
NCT02193191 (Phase I: recruiting) | Â | Â | |||
NCT03664830 (Phase I: recruiting) | Â | Â | |||
NCT04817345 (Phase II: recruiting) | Â | Â | |||
NCT05445128 (Phase II: recruiting) | Â | Â | |||
HSC transplantation with matched sibling donors | NCT01696461 (Phase II: completed) | Rapid and safe mobilization of sufficient numbers of HSCs from matched sibling donors. Engraftment was prompt & outcomes in recipients were encouraging | [327] | ||
Chronic granulomatous disease | NCT03547830 (Phase II: recruiting) | Â | Â | ||
Type 1 diabetes | NCT03182426 (Phase I/II: ongoing) | Â | Â | ||
Idiopathic CD4 lymphocytopenia | NCT02015013 (Phase II: recruiting) | Â | Â | ||
Balixafortide/ POL6326 (Polyphor) | CXCR4 antagonist | Breast cancer | NCT03786094 (Phase III: ongoing) | Â | Â |
PTX-9908/CTCE-9908 (TCM Biotech) | CXCR4 antagonist | Hepatocellular carcinoma | NCT03812874 (Phase I/II: recruiting) | Â | Â |
Motixafortide/ BL-8040 (BioLineRx) | CXCR4 antagonist | Healthy volunteers | NCT05293171 (Phase I: ongoing) | Â | Â |
Pancreatic cancer | NCT02826486 (Phase II: ongoing) | BL-8040 with immuno- and chemotherapy increased anti-tumor immune responses | [275] | ||
NCT02907099 (Phase II: ongoing) | Â | Â | |||
NCT04543071 (Phase II: recruiting) | Â | Â | |||
NCT03193190 (Phase I/II: recruiting) | Â | Â | |||
Gastric & esophageal cancer | NCT03281369 (Phase I/II: recruiting) | Â | Â | ||
Acute myeloid leukemia | NCT01838395 (Phase II: completed) | BL-8040 with chemotherapy increased survival & supported continued clinical development | [276] | ||
Multiple myeloma | NCT03246529 (Phase III: ongoing) | Â | Â | ||
Advanced hematological cancer | NCT02639559 (Phase II: ongoing) | Â | Â | ||
X4P-001/mavorixafor/ AMD11070/AMD070 (X4 Pharmaceuticals) | CXCR4 antagonist | WHIM syndrome | NCT03005327 (Phase II: ongoing) | Mobilization of neutrophils and lymphocytes & reduced infections | [282] |
NCT03995108 (Phase III: ongoing) | Â | Â | |||
Chronic neutropenia | NCT04154488 (Phase I: recruiting) | Â | Â | ||
Renal cell carcinoma | NCT02923531 (Phase I/II: completed) | Manageable safety profile, supporting further studies | [328] | ||
NCT02667886 (Phase I/II: ongoing) | Â | Â | |||
Waldenstrom’s macroglobulinemia | NCT04274738 (Phase I: ongoing) |  |  | ||
Breast cancer | NCT05103917 (Phase I/II: recruiting) | Â | Â | ||
Spiegelmer NOX-A12/ Olaptesed (TME Pharma) | RNA-oligonucleotide binding CXCL12 | Pancreatic & colorectal cancer | NCT03168139 (Phase I/II: completed) | NOX-A12 with immunotherapy was safe, supporting further clinical studies | [269] |
Chronic lymphocytic leukemia | NCT01486797 (Phase II: completed) | NOX-A12 with chemo- and immunotherapy was safe, supporting further clinical studies | [270] | ||
Multiple myeloma | NCT01521533 (Phase II: completed) | NOX-A12 with chemotherapy was safe, supporting further clinical studies | [271] | ||
Glioblastoma | NCT04121455 (Phase I/II: recruiting) | Â | Â | ||
ACT-1004–1239 (Idorsia) | ACKR3 antagonist | Healthy volunteers | NCT03869320 (Phase I: completed) | ACT-1004–1239 was safe & well tolerated supporting further clinical development | [279] |
NCT04286750 (Phase I: completed) | Favorable safety/tolerability and pharmacokinetic profiles, supporting further clinical development | [280] | |||
Ulocuplumab/ BMS-936564/ MDX-1338 (Bristol-Myers Squibb) | Anti-CXCR4 antibodies | Waldenstrom’s macroglobulinemia | NCT03225716 (Phase I/II: ongoing) | Support for further clinical development | [277] |
Multiple myeloma | NCT01359657 (Phase I: completed) | Ulocuplumab is safe & leads to a high response rate if combined with lenalidomide and dexamethasone | [278] |
