Phase I/IIa Combination Study of Bria-IMT™ with retifanlimab (INCMGA00012) and epacadostat in Advanced Breast Cancer
Recently awarded Fast Track status by the U.S. Food and Drug Administration (FDA), BriaCell is developing Bria-IMT™ in combination with immune checkpoint inhibitors in a clinical trial listed in ClinicalTrials.gov as NCT03328026. BriaCell is currently enrolling and dosing advanced breast cancer patients in its Phase I/IIa combination study of Bria-IMT™ with Incyte’s checkpoint inhibitor, retifanlimab, and its immunomodulator, epacadostat under corporate collaboration with Incyte.
Patients With advanced breast cancer will be eligible for combination therapy with retifanlimab and epacadostat if they have failed 2 or more prior lines of therapy.
Bria-IMT™ and retifanlimab and epacadostat Combination: Patients with advanced breast cancer will be treated with the combination of Bria-IMT™ and the anti-PD-1 antibody retifanlimab, similar to pembrolizumab (KEYTRUDA®; manufactured by Merck & Co.), and epacadostat, an orally bioavailable small-molecule inhibitor of indoleamine 2,3-dioxygenase 1 (IDO1).
More information on the roll-over combination study of Bria-IMT™ with retifanlimab and epacadostat will be available on ClinicalTrials.gov as NCT03328026.
Bria-IMT™ Phase I/IIa Combination Therapy Trial Design
Rationale for the combination study of Bria-IMT™ with retifanlimab and epacadostat
The immune checkpoint inhibitors such as pembrolizumab (KEYTRUDA®; anti-PD-1) have come to the forefront in the fight against cancer with substantial benefits for some patients. Most recently, the significance of immune checkpoint inhibitors was recognized by the Nobel committee by awarding Dr. Tasuku Honjo and Dr. James P. Allison with the 2018 Nobel Prize in Physiology or Medicine (Scientists behind game-changing cancer immunotherapies win Nobel medicine prize), validating the Company’s decision to launch a combination therapy with the immune checkpoint inhibitors.
Drs. Alison and Honjo independently, using different strategies, showed a new approach of treating patients by awakening certain cells of the immune system (T cells) to attack tumors. This new approach of treating patients with immune checkpoint inhibitors (such as KEYTRUDA®), designed to overcome immune suppression in cancer patients, is revolutionizing the fight against cancer.
In 2010 an important pre-clinical study by Dr. Allison’s group showed that combination with anti-PD-1 antibodies potentiated the tumor-destroying effect of melanoma cells engineered to produce granulocyte-macrophage colony-stimulating factor (GM-CSF), a substance that activates the immune system, compared to the treatment with the GM-CSF producing cells alone. Bria-IMT™ similarly uses a breast cancer cell line which produces GM-CSF. Bria-IMT™ has also been shown to indirectly and directly stimulate T cells, and hence boost the immune system. BriaCell has published these findings in a leading immunology journal. It is important to note that pembrolizumab and other similar immunotherapy drugs have not been shown to work on their own in breast cancer.
Retifanlimab is an anti-PD-1 antibody similar to KEYTRUDA®.