TEL AVIV, Israel—BioLineRx, a drug development company specializing in oncology and immunology, recently released results of a study pairing its BL-8040 peptide with Keytruda (pembrolizumab) from Merck & Co. (known as MSD outside the United States and Canada) as a potential treatment for metastatic pancreatic cancer. The results, reported at the European Society for Medical Oncology (ESMO) meeting recently, indicate that the COMBAT/KEYNOTE-202 study data show promising results in disease control and overall survival for patients in the trial.
According to principal investigator Dr. Manuel Hidalgo, a professor of medicine at Harvard Medical School and co-director of the Pancreatic Cancer Research Program at Beth Israel Deaconess Hospital, pancreatic cancer is one of the most difficult cancers to treat.
“Metastatic pancreatic cancer remains an area of very high unmet medical need, as currently approved treatments are limited by poor response rates and survival,” he says. “Despite recent advances in cancer treatment with immune checkpoint inhibitors in many tumor types, pancreatic cancer remains refractory to these treatment options.”
BioLineRx scientists have been developing a novel short peptide called BL-8040 because of its efficacy as a high-affinity antagonist for CXCR4, the most widely expressed chemokine receptor in human cancers. Specifically, in pancreatic cancer, high CXCR4 expression levels correlate with poor prognosis, contributing to the promotion of tumor growth, invasion, survival, angiogenesis and metastasis. In previous clinical trials, BL-8040 successfully mobilized immune cells to induce direct tumor cell death. In addition, clinical findings have demonstrated the ability of BL-8040 to mediate infiltration of T cells into tumors that were previously immunologically “cold” and devoid of immune cell infiltrate.
Simultaneously, Merck & Co. was developing Keytruda, a successful immune checkpoint inhibitor that produces anticancer effects by increasing the activity of T cells through blockade of the interaction between the immune checkpoint receptor PD-1 on T-cells and its ligand PD-L1 on tumor cells. Pancreatic cancers have very little T cell infiltration, making them less susceptive to checkpoint blockade than other tumors that are infiltrated by T cells.
In January 2016, BioLineRx entered into an immunotherapy collaboration with Merck and initiated the COMBAT/ KEYNOTE-202 study to test the hypothesis that combining BL-8040 with immune checkpoint blockade would increase the responsiveness of pancreatic cancer patients to immunotherapy. The Phase 2a study launched with 37 patients with metastatic pancreatic adenocarcinoma. The study data indicates that the combination therapy is safe and well tolerated, with demonstrated antitumor effects not seen using Keytruda alone.
According to Dr. Abi Vainstein, vice president of clinical and medical affairs at BioLineRx, the results are promising. “[Our] findings demonstrate the ability of BL-8040 to change the tumor microenvironment by increasing infiltration of tumor-reactive T cells and decreasing myeloid suppressive T cells. In addition, the results showed that the combination of BL-8040 with Keytruda elicits real clinical activity. These results were very encouraging for us, as the BL-8040/Keytruda combination demonstrated promising impact (especially in second-line patients) in patients with metastatic pancreatic cancer, one of the ‘coldest’ tumors there is.”
The researchers are looking ahead to the next phase in testing, by adding chemotherapy to the combination. Chemotherapy has been shown to reduce overall tumor burden while inducing immunogenic cell death, leading to activation and expansion of new tumor-reactive T cells. This suggests adding it to this cocktail may have even better therapeutic value. Regulatory submissions required to conduct the additional arm of the study have been made, and its initiation is planned for the fourth quarter of 2018.
“We believe BL-8040 can further facilitate the infiltration of these T cells into the tumor core, alongside the restoration of T cell activity within the tumor by Keytruda,” says Philip Serlin, CEO of BioLineRx. “We look forward to commencing the triple-combination arm of this important study by the end of this year, with results expected by the end of 2019.”
In other recent news, BioLineRx announced that the U.S. Food and Drug Administration (FDA) has granted the Biological Product Designation for AGI-134, the company’s novel immunotherapy compound, which is currently in the early stages of a Phase 1/2a study in solid tumors.
Said Serlin in early November, reporting on the company’s quarterly performance and financials: “We made significant progress during the third quarter and subsequent period advancing clinical development of both of our oncology programs—BL-8040 and AGI-134. The Phase 3 GENESIS study in stem-cell mobilization is now advancing in the randomized, placebo-controlled, part two of the trial. We are also rapidly moving forward in our expanded collaboration with Merck in pancreatic cancer, on the basis of the encouraging results recently presented at ESMO, with an additional cohort adding chemotherapy to the BL-8040/Keytruda combination. Further, we are very pleased to have initiated the first-in-human clinical study for AGI-134, our unique immunotherapy cancer vaccine. These achievements follow BL-8040’s very promising results in relapsed/refractory AML that were presented at the recent EHA Congress during the second quarter, showing significantly improved overall survival compared to historical data.”