The safety and efficacy of the following investigational compound or investigational use of the marketed product have not been established. The use has not been approved by the U.S. Food and Drug Administration or other regulatory authorities.
Motixafortide is being evaluated in two Phase 2 trials in combination with checkpoint inhibitor and chemotherapy as a first-line therapy in metastatic pancreatic cancer.
How Motixafortide Works
Motixafortide leverages the expression of the CXCR4 receptor on different immune cells and potentiates the immune system against the tumor. Among CXCR4-expressing immune cells, some exhibit anti-tumoral activity, such as effector T cells and some exhibit pro-tumoral activity and support tumor growth. By blocking the CXCR4 receptor, motixafortide was shown, in a Phase 2 study in pancreatic cancer patients, to enhance anti-tumoral activity and to ameliorate the following pro-tumoral activities:
- Releasing immune cells (NK, B, and T cells) to periphery by blocking their CXCR4-mediated retention in bone marrow stroma.
- Enabling infiltration of effector T cells into the tumor, by blocking their CXCR4-mediated retention on CXCL12-secreting fibroblasts at the edge of the tumor.
- Relieving immunosuppression by blocking CXCR4-mediated infiltration of immunosuppressor cells into the tumor.
Cancer Immunotherapy
Motixafortide modulates the effector/suppressor cell ratio toward a proinflammatory profile, which may act synergistically with checkpoint inhibitor agents to enhance the anti-tumor activity of infiltrated T cells.
Motixafortide modulates the effector/suppressor cell ratio toward a proinflammatory profile, which may act synergistically with checkpoint inhibitor agents to enhance the anti-tumor activity of infiltrated T cells.
SOLID TUMORS:Pancreatic Cancer
Pancreatic ductal adenocarcinoma (PDAC) is associated with poor patient outcomes because efficacious therapies do not yet exist. For all stages, the five-year survival rate is only twelve percent – the highest mortality rate in the U.S. among solid tumor malignancies – and globally, nearly a half million people will be diagnosed each year. Newer treatments like immunotherapy have limited efficacy, demonstrating a clear need to co-target alternative pathways.
Motixafortide is the most advanced CXCR4 antagonist in clinical development for metastatic PDAC and was successfully evaluated in the second part of the Phase 2 COMBAT study in combination with KEYTRUDA® (pembrolizumab) and chemotherapy (Onivyde plus 5-Fluorouracil/Leucovorin) as second-line treatment in patients with metastatic PDAC. Highly encouraging results demonstrated improvements across all study endpoints, including overall survival, progression-free survival, and overall response rate in patients with very advanced disease.
The triple combination was generally well tolerated, showing favorable safety and a low incidence of neutropenia and infections in treated patients.
Efficacy data from the Phase 2a study is summarized below:
| Combat/Keynote | Historical Data | |
|---|---|---|
| Median Overall Survival (mOS) | 6.5 months | 4.7 months1 |
| Median Progression Free Survival (mPFS) | 4.0 months | 2.7-3.1 months2,3 |
| Confirmed Objective Response Rate (cORR) | 13.2% | 7.7%3 |
| Disease Control Rate (DCR) | 63.2% | 29-52%2,4 |
1 Macarulla Mercade et al, Pancreas 2020
2 Petrelli el al Eu J Cancer 2017
3 Onivyde prescribing information
4 Wang Gilliam Eu J Cancer 2019
BioLineRx has initiated a collaboration to advance a randomized first-line metastatic PDAC clinical trial:
- In partnership with Columbia University, motixafortide is being studied in a randomized Phase 2 trial together with LIBTAYO® (cemiplimab) and chemotherapy as a first-line PDAC therapy.
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