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Chordoma

BN-BRACHYURY

PHASE 2


Our novel immunotherapy candidate, BN-Brachyury, utilizes a prime-boost vaccination regimen that has been optimized to include the gene for brachyury and other molecules known to increase immune activation. Brachyury is a transcription factor that is believed to play a prominent role in the metastasis and progression of tumors, and a key prognostic indicator of several common (e.g. colorectal, prostate, small cell lung, and triple negative breast cancer) and rare or orphan (e.g. chordoma, thyroid, neuroendocrine) cancers. Expression of brachyury is highly correlated with metastatic disease, poor overall survival, multi-drug resistance, and decreased survival rates.

A Phase 2 clinical trial is ongoing in patients with advanced chordoma. The multi-site trial, which holds the potential to serve as a registration trial, aims to determine if the combination of BN-Brachyury and the current standard of care, radiation therapy, results in a clinically meaningful objective response rate (ORR) within 12 months of radiation therapy, a timeframe during which historical controls show an ORR of less than 5% with radiation alone.

BN-Brachyury has received orphan drug status from the FDA in the treatment of chordoma.

Chordoma is a rare tumor that forms in the spine and base of the skull. 

It develops from a type of cell inside the bone called notochordal cells. During embryonic development, these cells make up an important structure, which is essentially the scaffolding on which the bones of the spine develop. In about 20% of the population they continue growing very slowly throughout one’s life and form small harmless tumors in the spine called benign notochordal cell tumors (BNCTs). Very rarely one of these BNCTs becomes cancerous and turns into a malignant tumor, which is called a chordoma. 

Currently, there are no approved drugs for the treatment of chordoma, and patients are truly limited in their options to control the disease, particularly in the advanced stage. The overall disease incidence of chordoma is low - with just 1,000 new cases reported in the U.S. and E.U. annually, and 10,000 people living with the disease.

Ongoing or planned trials

Phase 2 Trial of BN-Brachyury and Radiation Therapy in Patients With Advanced Chordoma
Location: USA
Read more: NCT03595228
Phase 1/2 Study of Immunotherapy Combination BN-Brachyury Vaccine, M7824, ALT-803 and Epacadostat (QuEST1)
Location: USA
Read more: NCT03493945

Redman JM, Steinberg SM, Gulley JL
Quick efficacy seeking trial (QuEST1): a novel combination immunotherapy study designed for rapid clinical signal assessment metastatic castration-resistant prostate cancer

J Immunother Cancer. 2018 Sep 18;6(1):91 

Heery CR, Gulley J, et al.
Phase I Study of a Poxviral TRICOM-Based Vaccine Directed Against the Transcription Factor Brachyury

Clin Cancer Res August 30 2017

Heery CR, Schlom J, et al.
Phase I, dose-escalation, clinical trial of MVA-Brachyury-TRICOM vaccine demonstrating safety and brachyury-specific T cell responses

J Immunother Cancer 2015, 3(Suppl 2):P132

Roselli M, Fernando RI, Guadagni F, et al.
Brachyury, a driver of the epithelial-mesenchymal transition, is overexpressed in human lung tumors: an opportunity for novel interventions against lung cancer.

Clin Cancer Res. 2012;18:3868-3879.

Kalluri R, Weinberg RA
The basics of epithelial-mesenchymal transition.

J Clin Invest. 2009;119:1420-1428.