• 04 Mar 2024
• Admin
• News Article

Biolinerx Begins Phase 2 Trial for Motixafortide

BioLineRx doses first patient in randomized phase 2 combination trial to evaluate CXCR4 inhibitor, motixafortide in pancreatic cancer

Overview

BioLineRx Ltd, a commercial stage biopharmaceutical company pursuing life-changing therapies in oncology and rare diseases, announced that the first patient has been dosed in the randomized CheMo4METPANC phase 2 combination clinical trial evaluating the company's CXCR4 inhibitor motixafortide, the PD-1 inhibitor cemiplimab and standard of care chemotherapies gemcitabine and nab-paclitaxel, versus gemcitabine and nab-paclitaxel alone, in first-line pancreatic cancer (PDAC). The investigator-initiated trial is being conducted in collaboration with Columbia University and is the first large, multi-center, randomized study evaluating motixafortide with a PD-1 inhibitor and first-line PDAC chemotherapies.

CEO from BioLineRx.

"Pancreatic ductal adenocarcinoma (PDAC) has had limited responses to traditional immunotherapy, resulting in a poor prognosis for patients and an urgent need for new treatment approaches," said Philip Serlin, chief executive officer of BioLineRx. "We are encouraged by our early pilot data and look forward to continuing to advance the expanded, randomized phase 2 CheMo4METPANC trial for patients living with this cancer."

Trial Results

• Findings from the single-arm pilot phase of the CheMo4METPANC trial will be shared by Dr. Manji at the 10th Annual Immuno-Oncology (IO) 360° Summit in Brooklyn, New York on February 29, 2024. 
• The findings were previously presented during an oral presentation at the American Association of Cancer Research (AACR) Special Conference on Pancreatic Cancer in Boston, Massachusetts, September 28, 2023. 
• As of July 2023, 7 of the 11 patients (64%) in the pilot phase experienced a partial response (PR) of which 5 (45%) were confirmed PRs at the time of the data cut; one patient experienced resolution of the hepatic (liver) metastatic lesion; and three patients (27%) experienced stable disease, resulting in a disease control rate of 91%.

About Motixafortide

• Motixafortide developed by BioLineRx is a lead therapeutic candidate, approved by the US FDA in September 2023, in combination with filgrastim (G-CSF), to mobilize hematopoietic stem cells for collection and subsequent autologous transplantation in patients with multiple myeloma, under the brand name APHEXDA. 
• Motixafortide is also being evaluated in a Phase 1 clinical trial evaluating motixafortide as a monotherapy and in combination with natalizumab for CD34+ hematopoietic stem cell (HSC) mobilization for gene therapies in sickle cell disease (SCD).

CheMo4METPANC Trials 

• CheMo4METPANC phase 2 clinical trial is a randomized, investigator-initiated clinical trial in first line metastatic pancreatic cancer. 
• Sponsored by Columbia University, and supported equally by BioLineRx and Regeneron, the study is evaluating the combination of CXCR4 inhibitor motixafortide, PD-1 inhibitor cemiplimab, and standard of care chemotherapies gemcitabine and nab-paclitaxel, versus gemcitabine and nab-paclitaxel alone, in 108 patients. 
• The trial's primary endpoint is progression free survival (PFS). Secondary objectives include safety, response rate, disease control rate, duration of clinical benefit and overall survival.

Pancreatic cancer: Epidemiology

• Pancreatic cancer has a low rate of early diagnosis and a poor prognosis. 
• In the United States in 2024, an estimated 66,000 adults will be diagnosed with the disease, which accounts for approximately 3% of all cancers in the US and about 7% of all cancer deaths. Worldwide, an estimated 496,000 people were diagnosed with the disease in 2020. 
• In the US, if the cancer is detected at an early stage when surgical removal of the tumor is possible, the 5-year relative survival rate is 44%. 
• About 12% of people are initially diagnosed at this stage. If the cancer has spread to surrounding tissues or organs, the 5-year relative survival rate is 15%.  
• For the 52% of patients who are initially diagnosed with metastatic cancer, the 5-year relative survival rate is 3%.2 In particular, hepatic (liver) metastases are a critical risk factor driving poor prognoses for patients with metastatic PDAC. These data highlight the need for the development of new therapeutic options.

Motixafortide Mechnaism

• Motixafortide inhibits CXCR4, a chemokine receptor and a well validated therapeutic target that is over-expressed in many human cancers including pancreatic ductal adenocarcinoma (PDAC). 

• 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-tumoural activity, such as effector T cells and some exhibit pro-tumoural 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-tumoural activity and to ameliorate the pro-tumoral activities by modulating the effector/suppressor cell ratio towards a proinflammatory profile.