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 1/2 Study of Immunotherapy Combination BN-Brachyury Vaccine, M7824, ALT-803 and Epacadostat (QuEST1) Location: USA Read more: NCT03493945 |
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Collins JM, Bilusic M, et al. Journal of Clinical Oncology 37, no. 15_suppl (May 20, 2019) 2640-2640. |
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Redman JM, Steinberg SM, Gulley JL |
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Heery CR, Schlom J, et al. |
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Roselli M, Fernando RI, Guadagni F, et al. |
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Kalluri R, Weinberg RA |