Stephen Hurly, President and Chief Executive Officer of Eleven Biotherapeutics said: "Despite current therapies and surgical regimens, there remains a large unmet need for patients with recurring or progressing NMIBC that is no longer responding to Bacillus Calmette-Guérin (BCG).
"While we remain internally focused on advancing our Phase 3 registration trial of Vicinium as a monotherapy, preclinical data suggests that Vicinium also has the ability to potentiate the activity of immuno-oncology agents. We are pleased to enter into this collaboration with the National Cancer Institute and AstraZeneca, which broadens the scope of our ongoing clinical program and enables us to evaluate Vicinium together with Imfinzi, a PD-L1 checkpoint inhibitor. We look forward to generating additional data, as we continue to advance Vicinium and work expeditiously to bring it forward as a new treaent option for patients with NMIBC."
Vicinium, like Eleven's other TPTs, is a single protein molecule composed of an antibody fragment genetically fused to a potent cytotoxic payload. Vicinium selectively binds to epithelial cell adhesion molecules (EpCAM), a cell surface marker that is highly expressed on many cancers, including high grade NMIBC, but that is present at minimal to no levels on healthy bladder tissue. After binding to EpCAM on the surface of the tumor cell, Vicinium is internalized into the cell where its potent cytotoxic cell killing payload, Pseudomonas Exotoxin A (ETA), is released, disrupting protein synthesis and leading to cell death.
At the American Association for Cancer Research Annual Meeting in April 2017, new preclinical data were presented demonstrating that cancer cells treated with VB4-845, the active pharmaceutical ingredient used to formulate Vicinium, undergo immunogenic cell death (ICD). ICD is known to stimulate host immune responses against cancer.
This supports the hypothesis that Eleven's TPTs not only directly kill tumor cells, but also induce a host immune cell-mediated anti-tumor response. This suggests that they are differentiated from existing treaents, and that they may have synergy with checkpoint inhibitors and other immuno-oncology compounds.
Under the terms of the CRADA, the NCI, led by principal investigator Dr. Piyush Agarwal of the NCI Center for Cancer Research, Urologic Oncology Branch, will conduct a Phase 1 clinical trial in patients with high-grade NMIBC to evaluate the safety, efficacy, and biological correlates of the Vicinium and durvalumab combination therapeutic strategy.
Vicinium is currently in a Phase 3 registration trial for the treaent of high-grade NMIBC. Eleven expects to complete patient enrollment in the second half of 2017, and to report topline 3-month data in the second quarter of 2018.
Imfinzi, in development by AstraZeneca and its biologic research arm, MedImmune, is a human monoclonal antibody directed against programmed death ligand-1 (PD-L1), that has accelerated approval by the FDA for the treaent of patients with locally advanced or metastatic urothelial carcinoma who have disease progression during or following platinum-containing chemotherapy, or have disease progression within 12 months of neoadjuvant or adjuvant treaent with platinum-containing chemotherapy, regardless of PD-L1 status.