Immunotherapy candidate targeting the metastatic process
BN-Brachyury is a novel cancer immunotherapy candidate with potential to treat chordoma (a rare tumor of the spine) as well as other metastatic cancers including triple negative breast cancer and non-small cell lung cancer which are known to have high expression levels of brachyury. Brachyury is a transcription factor that is reported to play a key role in the metastasis and progression of tumors. Tumors that overexpress brachyury are believed to be highly resistant to standard therapies, including radiation and chemotherapy, and are associated with decreased survival rates.
The product candidate consists of a primer (MVA-BN®) and a booster dose (fowlpox), which have been modified to express brachyury and to encode three costimulatory molecules, known as TRICOM. Bavarian Nordic has previously conducted a Phase 1 clinical trial of the primer vaccine (MVA-BN) in 38 patients with chordoma or metastatic solid cancers, which showed the vaccine to be well-tolerated and to induce brachyury-specific T-cell immune responses in the vast majority of patients.
In early 2018, the Company initiated an open-label Phase 1 trial to evaluate the safety and tolerability of the MVA‑BN® Brachyury vaccine, followed by a brachyury encoded fowlpox (FPV) booster in patients. The trial will enroll up to 10 patients with metastatic or unresectable, locally advanced malignant solid tumors. Patients will receive two prime doses of MVA-BN Brachyury, followed by multiple booster doses with FPV-Brachyury. The primary endpoint of the study is safety and tolerability, and secondary endpoints include immunologic responses as measured by an increase in brachyury-specific T-cells and other tumor-associated antigens, as well as evidence of clinical benefit such as progression-free survival (PFS) and objective response (OR).
In November 2018, the Company initiate a Phase 2 study that combines the vaccine with radiation in patients with advanced chordoma. The Company has obtained orphan drug status with the FDA for this indication and could also be eligible for the FDA’s Orphan Products Clinical Trials Grants Program which supports the clinical development of products for use in rare diseases or conditions where no current therapy exists. At the appropriate time, the Company will also apply for a Breakthrough Therapy Designation with the FDA.