Triple-Combination Immunotherapy for Triple-Negative Breast Cancer: UbiVac and BMS Partner on DPV-001 Cancer Vaccine with Anti-OX40 and Anti-PD-1 Therapy

June 10, 2020 /Bioon/ -- Cancer vaccine developer UbiVac and Bristol-Myers Squibb (BMS) recently announced a clinical trial collaboration to evaluate the safety, tolerability, and preliminary efficacy of DPV-001, a first-in-class cancer vaccine developed using autophagy technology, in combination with BMS’s immuno-oncology drug, the anti-OX40 therapy BMS-986178, followed by sequential treatment with the anti-PD-1 therapy Opdivo (generic name: nivolumab).

The two parties will initiate a Phase Ib multicenter trial to test the hypothesis that a combination immunotherapy regimen comprising the DPV-001 cancer vaccine, anti-OX40 therapy, and anti-PD-1 therapy can enhance anticancer immunity in patients with advanced triple-negative breast cancer (TNBC).

Triple-Negative Breast Cancer (TNBC) specifically refers to breast cancer that is negative for estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). This is an aggressive form of breast cancer characterized by rapid progression, poor prognosis, high recurrence rates, and a 5-year survival rate of less than 15%. TNBC is unresponsive to hormonal therapy and HER2-targeted therapies (such as Herceptin), leaving very limited clinical treatment options primarily reliant on chemotherapy. Metastatic TNBC is among the most aggressive and difficult-to-treat forms of breast cancer. TNBC often metastasizes frequently and occurs in younger patients (<50 years old) and those carrying hereditary BRCA mutations.

This newly initiated clinical trial is the first to evaluate the combination of a cancer vaccine (DPV-001) and a T-cell agonist (BMS-986178). DPV-001 is designed to educate the immune system to destroy cancer cells, while BMS-986178 aims to enhance immune system activity. During the trial, patients will also receive treatment with Opdivo, an anti-programmed death receptor-1 (PD-1) immune checkpoint inhibitor intended to release the brakes on the immune system.

Dr. Bernard A. Fox, President and Chief Executive Officer of UbiVac, stated, “UbiVac is pleased to collaborate with Bristol-Myers Squibb, a global leader in immuno-oncology, to investigate this innovative cancer vaccine in combination with anti-OX40 and checkpoint blockade, and to evaluate whether this regimen can enhance anti-tumor immunity in patients with advanced triple-negative breast cancer. We believe that this cutting-edge immunotherapy combination has the potential to induce durable anti-cancer immunity and translate into clinical responses for patients with triple-negative breast cancer.”

DPV-001, developed on the DRibble vaccine platform, is UbiVac’s lead biologic agent. It is a dendritic cell (DC)-targeting microvesicle containing short-lived proteins that are believed to represent dominant HLA-presented epitopes on the surface of cancer cells. These microvesicles are packaged with various TLR and NOD agonists, 15 types of DAMPs, and chaperone molecules. This microvesicle vaccine also contains over 100 proteins overexpressed in triple-negative breast cancer (TNBC), as well as up to 1,700 allosteric peptide ligands (APLs) that enhance immunity against cancer antigens. This formulation drives B cells, CD4+ and CD8+ T cells, and innate components of the host immune system to mediate anti-cancer effects.

In preclinical models,DPV-001Can Convert "Cold Tumors" into "Hot Tumors""Cold" tumors refer to tumor tissues with no or very few immune cells, while "hot" tumors are characterized by immune cell infiltration within the tumor tissue. In cancer treatment, converting "cold" tumors into "hot" tumors is critically important, as many human tumors are considered unresponsive to immunotherapy due to a lack of immune cells capable of recognizing cancer cells within the tumor tissue, thereby classifying them as "cold" tumors.

Dr. Hong-Ming Hu, Chief Scientific Officer of UbiVac, stated, “Based on these data, we believe that the DRibble platform vaccine technology combined with anti-OX40 will ignite the immune system in patients with ‘cold’ tumors, transforming them into ‘hot’ tumors that are more sensitive to checkpoint inhibitors.” (Bioon.com)

Original Source: UbiVac Announces Clinical Trial Collaboration with Bristol Myers Squibb on Combination Immunotherapy for Advanced Triple Negative Breast Cancer