As it turns out, more than three-fourths (77%) of those patients suffering from stage IV metastatic pancreatic adenocarcinoma (pancreatic cancer) and treated with a protocol developed by an Israeli-based biopharmaceutical company are able to get their disease under control, according to the results of an ongoing study. The investigational therapy is called BL-8040.
Pancreatic Cancer is a Killer
Pancreatic cancer is a killer with a 3% survival rate over a five-year period. Most patients die within a few months to half a year. Moreover there have been few advances in pancreatic cancer treatment over the past decade. It represents the only cancer within the top 5 that is seeing death rates rising. Pancreatic cancer spells trouble as 1) it is most often diagnosed at a later stage and B) it has developed mechanism enabling it to project itself from the human body’s immune system.
What is BL-8040?
BL-8040 is a 14-amino acid synthetic cyclic peptide, is a novel, best in class, high-affinity CXCR4 antagonist with long receptor occupancy (>48 hours) and extended CXCR4 inhibition. BL-8040 is developed for the treatment of solid tumors, hematological malignancies and indications requiring hematopoietic stem cell transplantation. BL-8040 pipeline is based on the vital roles of CXCR4-CXCL12 (SDF-1) interactions in oncologic processes (growth, invasion, survival, angiogenesis and metastasis) in various cancer types and in the maintenance of hematopoietic stem cells, immune cells and hematopoietic cancer cells in their protective niche.
The data results from BioLineRX’s Phase IIa COMBAT/KEYNOTE-202 study, which reveals double the positive effect on the treatment of pancreatic cancer as compared to the approved second-line chemotherapy treatment for the disease. This study will assess the efficacy and safety of BL-8040 in combination with pembrolizumab (Keytruda®) and BL8040/ Pembrolizumab in combination with liposomal irinotecan (Onivyde®)/5-fluorouracil/leucovorin (5-FU/LV) in subjects with metastatic pancreatic adenocarcinoma. The study is a result of a 2016 deal inked between BioLineRx and Merck in 2016.
32% of patients participating in the study who could be evaluated saw a reduction in tumor size (of more than 30% from baseline), as opposed to 17% of patients treated with chemotherapy, based on historical data. Moreover, 45% of patients were able to stabilize the disease—meaning although the tumor didn’t reduce in size it didn’t grow either during the study. CEO of sponsor BioLineRx, Philip Serlin, reported “That means 77% of patients were able to achieve disease control state.” This compared to 52% of patients who were treated with chemotherapy alone, reported the Jerusalem Post.
The Post reported that it cannot be determined as of yet if the study will produce longer progression-free survival. The CEO of the Israeli sponsor reports that they hope to have more data points on median overall survival by mid-2020. But Serlin did note that at least with some patients already survived with the treatment for more than 330 days—representing a substantial improvement for the diagnosed with state IV metastatic pancreatic cancer who have failed first-line treatment.
The Keytruda Connection
Merck partnered with BioLineRx as it was seeking to find a compelling way to take on pancreatic cancer. But paired with BL-8040—administered in combination with Keytruda might reveal better results. In this triple combination arm protocol, patients receive BL-8040 monotherapy priming treatment for five days—later followed by combination cycles of chemotherapy (Onivyde/5-flouroucil/leucovorin), Keytruda and BL-8040 until progression. A complex regimen but one tailored for patients that are incredibly sick.
Clinical Investigator Comment
Dr. Manuel Hidalgo, chief of the Division of Hematology and Medical Oncology and a senior member of the Sandra and Edward Meyer Cancer Center at Weill Cornell Medicine and New York-Presbyterian/Weill Cornell Medical Center, not to mention principal investigator of the study, noted, “The results are even stronger when taking into account the extended durability of clinical benefit seen to date in this study (medial of 7.8 months), compared to approximately three months of response duration with other treatments for second-line pancreatic cancer.” He continued, “I will look forward to the survival data expected in mid-2020.”
Dr. Manuel Hidalgo, chief of the Division of Hematology and Medical Oncology and a senior member of the Sandra and Edward Meyer Cancer Center at Weill Cornell Medicine and New York-Presbyterian/Weill Cornell Medical Center