Turn a "cold tumor" into a "hot tumor"! New CXCR4 antagonist motixafortide to treat pancreatic cancer shows strong results!

December 18, 2020 // -- BioLineRx is a late-clinical biopharmaceutical company focused on the development of innovative oncology drugs.
, the company recently released data from the ongoing Phase IIA COMBAT/KEYNOTE-202 study triple therapy queue for pancreatic cancer.
the team evaluated the efficacy and safety of motixafortide (BL-8040) and the anti-PD-1 therapy Keytruda (Corinthian, generic name: pembrolizumab, paboliju monotherapy) and chemotherapy, as well as the second-line treatment of stage IV pancreatic catheterization (PDAC).
the group included 43 patients who were initially diagnosed with non-excisive phase IV metastasis PDAC, who progressed after receiving first-line treatment under the Gissitham programme.
the study, the team received a combination of motixafortide (BL-8040) single-drug pre-exciting treatment for 5 days, followed by motixafortide, Keytruda, chemotherapy (Onivyde/5-FU/leucovorin, elixirate lipids/5-fluorouracil/calcium left-handed folate) triple combination therapy until the disease progressed.
end point of the study was objective mitigation rate (ORR), and secondary endpoints included: confirmed objective mitigation rate (cORR), total lifetime (OS), progress-free survival (PFS), and disease control rate (DCR).
results showed that the motixafortide-Keytruda-chemotherapy triple-combination programme showed a significant improvement over the historical results of all study endpoints.
results of triple cohorts in this study: OrR for triple therapy was 21.2% (historical data: 16%), cORR was 13.2% (historical data: 7.7%), and medium out of 38 patients who could be evaluated OS is 6.5 months (historical data: 4.7 months), the medium PFS is 4.0 months (historical data: 2.7-3.1 months), and DCR is 63.2% (historical data: 29-52).
study, the triple program was generally well-to-do and consistent with the safety of each drug.
adverse events (AEs) and severe adverse events (SAEs) are consistent with chemotherapy-based treatment options.
note that the triplets of motixafortide, Keytruda, and chemotherapy show some safety advantages compared to the historical data related to specific chemotherapy used in this study.
these safety benefits include a lower risk of level 3 neutral granulocyte reduction (7% vs 20% (historical data)) and a lower rate of level 3 infection (7% vs 17% (historical data) than historical data. "These results are very encouraging because PDAC patients in this research team are a very challenging group of patients," said Dr. Manuel Hidalgo, lead investigator on the
COMBAT/KEYNOTE-202 study and director of the Department of Hematology and Medical Oncology at the Weill Cornell School of Medicine.
all patients were diagnosed during stage IV, and more than 70% had liver metastasis, which was a key factor in the very poor prognosis.
we are very pleased with these results, and the data are significantly improved at all study endpoints compared to historical data.
consistency improvement at all study endpoints was a key differentiator relative to other compounds, which improved at only one endpoint in the initial study and ultimately failed in late-stage clinical studies.
these positive results were further supported by the long-lasting, medium clinical benefit period of up to 5.6 months that we observed in this trial.
addition, we believe these results clearly support the combination of the motixafortide/Immune Checkpoint Inhibitor Platform with other standard nursing chemotherapy in the early PDAC treatment phase and other 'cold' solid tumors.
For this reason, we are currently working on motixafortide combination anti-PD-1 therapy and chemotherapy (gisitapon and nab yew alcohol) for first-line treatment of pancreatic cancer, and we are also evaluating potential combinations for other solid tumor adaptations.
"motixafortide mechanism: turning a "cold" tumor into a "hot tumor" (click on the image to see the graph) motixafortide targets CXCR4, a chemicalation factor subject and a proven therapeutic target that is overexposed in many human cancers, including PDAC.
CXCR4 play a key role in tumor growth, invasion, angiogenesy, metastasis and therapeutic resistance, and the overexposing of CXCR4 is associated with poor prognosmation.
motixafortide is a short synthetic peptide that serves as a platform for cancer treatment and has unique features that give it the potential to be the best-in-class CXCR4 antagonist.
motixafortide showed high affinity, long subject share, and acted as a reverse excitant.
In many clinical and preclinical studies, motixafortide has been shown to affect "cold" tumors in a variety of modes of action, including immunocellular migration, immuno-effect T-cell immersion of tumors, reduction of immunosuppressive cells (such as MDSCs) in tumor microencology, and "hot" "hot" tumors (i.e., making them sensitive to immunosuppressants and chemotherapy).
motixafortide is a pilot project for BioLineRx, a cancer treatment platform, and is currently working with Mercadon on a Phase IIa study to evaluate the motixafortide-Keytruda-chemotherapy triple combination.
addition, motixafortide is also conducting a Phase IIb study (consolidation of acute myeloid leukemia (AML)) and a Phase III study (stem cell mobilization for an introphy bone marrow transplant).
, the company is also working with Roche's GeneNate to evaluate the motixafortide combination anti-PD-L1 therapy Tecentriq (Tershanqi, generic name: atezolizumab, Atzhu monoantigen) combination therapy in two Ib/II solid tumor studies.
In addition to motixafortide, BioLineRx is also developing a second oncology project, AGI-134, an immunotherapy for multiple solid tumors that is currently clinical in Phase I/IIa.
() Source: BioLineRx Announces Final Results from Phase 2a COMBAT/KEYNOTE-202 Triple Study of Motixafortide in Second Line Metastatic Pancreatic Cancer (PDAC) <!--/ewebeditor:page->