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 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.
COMBAT Phase 2a Study | Proof-of-Mechanism, Initial Safety and Efficacy in a Cohort of Patients with Second-Line Disease
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.
In patients with very advanced disease, results from the COMBAT study demonstrated improvements across all endpoints compared to available historical control data, including overall survival, progression-free survival, and overall response rate.
The triple combination was generally well tolerated, showing favorable safety and a low incidence of neutropenia and infections in treated patients.
6.5months
Median Overall Survival
compared to 4.7 months based on historical data1
Median Overall Survival
compared to 4.7 months based on historical data1
4months
Median Progression Free Survival
compared to 2.7-3.1 months based on historical data2,3
Median Progression Free Survival
compared to 2.7-3.1 months based on historical data2,3
The combination was well tolerated and showed a favorable safety profile
There was a low incidence of infections in treated patients
1 Macarulla Mercade et al, Pancreas 2020
2 Petrelli el al Eu J Cancer 2017
3 Onivyde prescribing information
CheMo4METPANC Randomized Phase 2b Study In Patients with First-Line Disease
With proof-of-mechanism and concept established in the COMBAT Phase 2a clinical trial, motixafortide is now being studied in a large, randomized Phase 2b trial in partnership with Columbia University and supported equally by BioLineRx and Regeneron.
The multi-center trial is evaluating the combination motixafortide, PD-1 inhibitor LIBTAYO® (cemiplimab), and standard of care chemotherapies gemcitabine and nab-paclitaxel, versus gemcitabine and nab-paclitaxel alone in 108 patients. The study’s primary endpoint is progression-free survival and secondary objectives include safety, response rate, disease control rate, duration of clinical benefit and overall survival.
Preliminary efficacy data from the single-arm pilot phase of the CheMo4METPANC study with 11 patients was promising and prompted an amendment to the trial design to become a randomized study.
Pilot phase conclusions are summarized below (as of July 2023):
64%
Overall Response Rate4
Overall Response Rate4
9.6months
Median Progression Free Survival4
Median Progression Free Survival4
One patient experienced resolution of hepatic (liver) metastatic lesion4
The combination demonstrated a tolerable safety profile4
No unexpected Grade 4 or 5 treatment related adverse events4
4Manji, GA AACR Pancreatic Cancer 2023 (as of July 20,2023)
To see additional data and information on our PDAC programs, please see our investor deck
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