Date: 2016-11-14
Type of information: Presentation of results at a congress
phase: preclinical
Announcement: presentation of results at the Society for Immunotherapy of Cancer (SITC) 2016 Annual Meeting, which was held November 9-13, 2016 in National Harbor
Company: Peregrine Pharmaceuticals (USA - CA)
Product: phosphatidylserine (PS)-targeting antibodies similar to bavituximab, anti-PD1 therapies, anti-LAG3 therapies and radiation therapies
Action
mechanism: immune checkpoint inhibitor/monoclonal antibody. Bavituximab is a chimeric monoclonal antibody that targets phosphatidylserine (PS). Signals from PS inhibit the ability of immune cells to recognize and fight tumors. Bavituximab blocks PS to alter this immunosuppressive signal and send an immune activating signal. Targeting PS with bavituximab has been shown to shift the functions of immune cells in tumors, resulting in anti-tumor immune responses.
Disease:
Therapeutic area: Cancer - Oncology
Country:
Trial details:
Latest
news: * On November 14, 2016, Peregrine Pharmaceuticals announced the presentation of positive data from multiple new preclinical studies of the company's phosphatidylserine (PS)-targeting antibodies. Study results highlight that PS-targeting antibodies similar to bavituximab synergize with checkpoint inhibitors and radiation to improve anti-tumor activity in various animal tumor models. Importantly, the improved anti-tumor activity seen in these studies was even greater when PS-targeting therapy was a part of triple combination treatment including anti-PD-1 and another therapy. Data were presented by Peregrine scientists, as well as researchers from Memorial Sloan Kettering Cancer Center (MSK), at the Society for Immunotherapy of Cancer (SITC) 2016 Annual Meeting, which was held November 9-13, 2016 in National Harbor , MD.
Initial results from Peregrine's ongoing collaboration with MSK researchers were featured in a poster presented by Sadna Budhu , Ph.D., at SITC 2016. A team of MSK researchers led by cancer immunotherapy thought-leaders, Taha Merghoub , Ph.D. and Jedd D. Wolchok , M.D., Ph.D., evaluated the effects of combining PS-targeting, anti-PD-1 and radiation therapies in the mouse B16 melanoma model. Study data showed that PS-targeting antibodies synergize with both anti-PD-1 and radiation therapy to improve anti-cancer activity. PS-targeting treatment in combination with radiation, as well as triple combination of PS-targeting treatment, anti-PD-1 and radiation, led to a reduction in tumor burden. Median survival for the triple combination treatment still had not been reached at the end of the 80-day observation period with other arms in the study showing median survival that ranged from 24-70 days.
Researchers also evaluated the impact of the PS-targeting and radiation combination treatment on the level and type of immune activity. These results demonstrated that the combination led to a change in the tumor microenvironment, shifting it from immunosuppressive in which tumors are protected to immune active in which tumors are more susceptible to treatment. Analysis of local immune responses in the tumors of the treated animals showed that the combination treatment increased the number of tumor associated macrophages and shifted the macrophage polarization from the immunosuppressive M2 type to the immune active M1 type. When systemic immune responses were analyzed following triple combination of PS-targeting treatment, anti-PD-1 and radiation, researchers also saw evidence of increased immune activity. This was illustrated by key indicators of immune activity, including increases in CD8+ T-cell activation, effector cytokine production and differentiation into effector memory cells.
A second study, conducted by Peregrine, evaluated the effects of combining PS-targeting, anti-PD-1 and anti-LAG3 therapies in the E0771 triple negative breast cancer (TNBC) model. Initial findings from this study were previously reported and demonstrated that eight of the ten (80%) animals receiving the PS-targeting, anti-PD-1 and anti-LAG3 treatment combination experienced complete tumor regressions, whereas there were no animals (0/10) in the anti-PD-1 and anti-LAG3 combination treatment arm that had a complete regression. New data presented for the first time at SITC demonstrated that the triple combination established a specific and prolonged anti-tumor immune response which protected those eight animals that achieved a complete tumor regression against a re-challenge with the same E0771 TNBC model tumor cells. This sustained anti-tumor response demonstrates the ability of the triple combination treatment to trigger immune system memory and support adaptive immune responses against reemerging disease in the E0771 TNBC model.
Further highlighting the immune impact of the PS-targeting/anti-PD-1/anti-LAG3 treatment combination were initial results of a new analysis from this study using the nCounter® PanCancer Immune Profiling Panel from NanoString Technologies®. Data from the analysis demonstrated that the triple combination induced a greater shift in the tumor microenvironment from immunosuppressive to immune active as compared to all other treatment groups. This was evidenced by greater increases in the activity of several critical immune activating pathways, including presentation and processing of antigens and signaling and activation of T-cells, for the triple combination as compared to all other treatments.
Peregrine's clinical development strategy for bavituximab currently focuses on small, early-stage, proof-of-concept trials evaluating the drug in combination with other cancer treatments. This approach includes the recently announced grants awarded by the National Comprehensive Cancer Network (NCCN) to support three different clinical trials of bavituximab treatment combinations. These trials will evaluate novel bavituximab combinations in glioblastoma, head and neck cancer, and hepatocellular carcinoma including an immunotherapy combination. Additionally, Peregrine continues to advance its pre-clinical collaboration with Memorial Sloan Kettering Cancer Center with the goal of evaluating combinations of bavituximab with other checkpoint inhibitors and immune stimulatory agents. The intent behind this strategy is to focus our research and development spending to further validate bavituximab's combination potential as we seek to advance the program though a pharmaceutical or biotechnology partner.
