TEL AVIV, Israel—BioLineRx, working in conjunction with Merck & Co. Inc. (known as MSD outside the United States and Canada), has announced positive results from its triple combination arm of the COMBAT/KEYNOTE-202 study, which is seeking better treatment options for patients with metastatic pancreatic adenocarcinoma (PDAC). This second-line study administered a regimen of BL-8040 in combination with pembrolizumab and a chemotherapy combination of Onivyde, 5FU and leucovorin to patients diagnosed with stage IV PDAC who had failed to see promising long-term results in their first-line treatment approach.
“While the study is not complete,” says Philip Serlin, CEO of BioLineRx, “these initial results are particularly encouraging in terms of overall response, disease control and durability of responses against the backdrop of a disease indication of PDAC—which is one of the most difficult cancers to treat, with an extremely poor prognosis upon diagnosis.”
The three-pronged approach adds BioLineRx’s BL-8040 to the previously utilized pembrolizumab, an immunotherapy treatment known commercially as Keytruda, coupled with chemotherapy. BL-8040 is a short synthetic antagonist of CXCR4, a chemokine receptor known to be over-expressed in many human cancers, including PDAC. CXCR4 plays a key role in tumor growth, invasion, angiogenesis, metastasis and therapeutic resistance, and CXCR4 overexpression has been shown to be correlated with poor prognosis. Adding BL-8040 shows a tolerable safety profile which compares favorably with that of the individual components alone. The overall response rate of 32 percent, coupled with a 77-percent disease control rate, is a substantial improvement to the current second-line chemotherapy standard of care, which reports 17 percent and 52 percent, respectively.
“Metastatic pancreatic cancer has a very poor response to chemotherapy, and immunotherapy treatments have failed to show any effect as single agents,” explained Dr. Manuel Hidalgo, principal investigator of this study and 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. “These promising initial results presented today show an overall response rate almost double the current chemotherapy standard-of-care treatment in second-line patients. The results are even stronger when taking into account the extended durability of clinical benefit seen to date in this study (median of 7.8 months), compared to approximately three months of response duration with other treatments for second-line pancreatic cancer. I look forward to the survival data expected in mid-2020.”
The durability of the results is of particular interest, with highly anticipated progression-free survival data. While the current length of the study does not allow for firm data, the researchers are bullish based on the few patients now approaching a full year of treatment who are responding and experiencing a mild enough toxicity to keep them in the study. Approximately 10 percent of patients experience a grade 3/4 toxicity, which is in line with other treatment modules.
“We are very excited by the positive data accumulating from this triple combination arm of our Phase 2a pancreatic study under our collaboration with Merck,” Serlin remarked. “These data continue to confirm our hypothesis relating to the synergistic effect of cytotoxic chemotherapy, along with the trafficking, tumor microenvironment modulation and T-cell infiltration effects seen in PDAC patients from previous dual combination trials of BL-8040 with checkpoint inhibitors. It is therefore very encouraging to see robust and durable responses to the triple combination treatment, especially as we continue to see a trend of patients receiving treatment for an extended period that move from stable disease to partial response. We hope to see these results translate into an extended survival benefit for these patients, which we expect to announce in mid-2020, and we hope will pave the way for use of immunotherapy in pancreatic cancer and in other cold tumors.”
BioLineRx intends to initiate conversations with regulatory agencies in early 2020 to reach an agreement about the fastest and most efficient route to expand clinical trials for this triple-arm approach. In addition, BioLineRx is exploring other applications for BL-8040, which is also being evaluated in a Phase 2b study in consolidation acute myeloid leukemia and a Phase 3 study in stem cell mobilization for autologous bone-marrow transplantation. The company also has an ongoing collaboration agreement with Genentech, a member of the Roche Group, to evaluate BL-8040 in combination with Genentech’s atezolizumab in two Phase 1b/2 solid tumor studies.