Clinical Trials

Phase I/II Combination Study of Bria-IMT™ with retifanlimab (INCMGA00012) 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 randomized Phase II combination study of Bria-IMT™ with Incyte’s checkpoint inhibitor, retifanlimab, under corporate collaboration with Incyte.

Patients With advanced breast cancer will be eligible for combination therapy with retifanlimab if they have failed 2 or more prior lines of therapy.

Bria-IMT™ and retifanlimab 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.).

More information on the roll-over combination study of Bria-IMT™ with retifanlimab will be available on ClinicalTrials.gov as NCT03328026.

Rationale for the combination study of Bria-IMT™ with retifanlimab

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.

Bria-IMT™ 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. Incyte’s retifanlimab is an anti-PD-1 antibody similar to KEYTRUDA®.

BriaCell conducted two Proof of Concept trials using Bria-IMT™ in metastatic breast cancer patients who had failed multiple prior treatments. The trial produced a median overall survival of 35 months and at least one “robust responder with >90% regression during treatment, subsequent relapse (upon halting treatment) responded to re-treatment. These findings were confirmed in another study of 23 patients with advanced breast cancer showing clinical benefit and tumor regressions in predictable subsets of patients. Based on these findings, the combination study with PD-1 inhibitors was initiated.

We conducted three Proof of Concept clinical trials, one using parental SV-BR-1 cells and the other two using Bria-IMT™ (i.e., genetically engineered SV-BR-1 cells – producing GM-CSF), in metastatic (i.e., Stage IV) breast cancer patients who had failed prior treatments. The patients were treated, and the results are summarized below.

First Proof of Concept Trial:

  • Used unmodified cell line  (parental SV-BR-1 cells) + GM-CSF + cyclophosphamide
  • N = 14 late stage, treatment-refractory breast cancer patients
  • No significant adverse treatment-associated events, well tolerated
  • Median Overall Survival = 12.1 months

For further details, please see: BriaCell Dr. Charles Wiseman Article Phase I Trial-14 Patients

Second Proof of Concept Trial:

  • Used Bria-IMT™ (genetically engineered SV-BR-1 cells – producing GM-CSF) + cyclophosphamide + interferon-α
  • N = 4 late stage, treatment-refractory (3 breast cancer, and 1 ovarian cancer) patients
  • No significant adverse treatment-associated events, well tolerated
  • Median Overall Survival = 35 months
  • One robust responder with >90% regression during treatment, subsequent relapse (upon halting treatment) responded to re-treatment

A case report was published. For details, please see: BriaCell Article Clinical Regression

Third Proof of Concept Trial:

Data (23 patients)- Phase I/II Study (2017-2018)

  • Bria-IMT™ has been very well tolerated (≥60 doses given to date)
  • The majority of adverse events (AEs) were limited to expected minor local irritation at the injection sites

  • No related grade >3 or unexpected AEs
  • No related serious AEs
  • No serious, unexpected, related AEs

    • Most patients who have dropped out did so due to worsening of their underlying disease

  • Bria-IMT™ appears to be most effective in patients who match with Bria-IMT ™ at 2 HLA loci (types) further supporting our “HLA Matching Hypothesis”, and the development of Bria-OTS ™ to cover 90% of the patient population.

    • Combination with immune checkpoint inhibitors may induce a more potent anti-cancer response, leading to our strategy of combination studies of Bria-IMT™ with KEYTRUDA®