BriaCell, an immuno-oncology focused biotechnology company with a proprietary targeted immunotherapy technology, has provided a clinical update regarding its ongoing clinical trials of Bria-IMT™ (formerly referred to as SV-BR-1-GM).
BriaCell currently is enrolling patients in two separate but related clinical trials. Trial WRI-GEV-007 (listed in ClinicalTrials.gov as NCT03066947) is a Phase I/IIa clinical study designed to evaluate the safety and efficacy of Bria-IMT™ in metastatic or locally recurrent breast cancer patients. In this study, Bria-IMT™ is given in a regimen including low-dose pre-dose cyclophosphamide (to reduce suppression of the immune response) and post-dose interferon-alpha (to boost the immune response). The second clinical trial, BRI-ROL-001 (listed in ClinicalTrials.gov as NCT03328026), is a rollover study of Bria-IMT™ in combination with Keytruda® [pembrolizumab] or Yervoy® [ipilimumab].
Patient recruitment is on schedule despite interruption due to temporary shutdown of some clinical sites, affected by wildfires and hurricanes. Seven patients have enrolled in the WRI-GEV-007 clinical trial with 6 treated to date (1 patient dropped out after cyclophosphamide pre-treatment and did not receive Bria-IMT™). Based on results to-date, Bria-IMT™ has been very well tolerated and the majority of adverse events were limited to expected minor local irritation at the injection sites. No serious adverse events related to Bria-IMT™ have been reported and no new or unexpected safety issues related to Bria-IMT™ have been observed. The Phase I portion of the study has been successfully completed, and the Phase IIa portion is currently enrolling.
One patient is worth discussing in detail. This 73-year-old woman had breast cancer diagnosed in 1995. She developed liver metastases in 2010, and then lung metastases in 2017. Prior treatments included surgery, radiation therapy, hormonal therapy and seven rounds of chemotherapy with 8 different chemotherapy agents. She received 5 cycles of Bria-IMT™ over the first 3 months of treatment, then 3 additional cycles over the following 3 months (6 months total). Evaluation was performed after 3 months and 6 months. After 3 months, despite the extensive prior therapy, her scans noted that, “there has been a clear response in the multiple bilateral pulmonary nodules” indicating that several lung tumors had disappeared or decreased in size. This response was maintained after 6 months of treatment with Bria-IMT™. The liver tumors were stable to slightly increased at 3 months, and then progressed after 6 months.
Like the patient reported previously by Dr. Wiseman, BriaCell’s Scientific Founder, in a proof-of-concept clinical study, this patient is a double match with Bria-IMT™ at two specific biomarkers (HLA-A and HLA-DRB3). This is highly significant, as it supports our BriaDX™ hypothesis that these biomarkers can be used to select the patients most likely to respond to Bria-IMT™ therapy. We also noted in this patient that, while circulating tumor-associated cells decreased following the initial treatment, the expression of PD-L1, a molecule that suppresses the immune response, increased during treatment. This suggests that treating this patient (and other similar patients) with Bria-IMT™ in combination with a potent PD-1 inhibitor such as Keytruda® [pembrolizumab] may be a highly effective method to improve the efficacy of the treatment and patient outcomes.
A third clinical site was recently added to the study and several patients are being evaluated for the WRI-GEV-007 study. Discussions are ongoing with two additional clinical sites which are expected to be added in the near future. The combination rollover study, BRI-ROL-001, is available to enroll patients.
Other activities remain on track. The companion diagnostic, BriaDX™, has been bolstered by the important supporting data for the HLA biomarker matching hypothesis noted above. BriaCell is also developing an off-the-shelf, personalized immunotherapy (Bria-OTS™) to treat a much wider patient population (with ~90% of the population being a double-match with Bria-OTS™). In collaboration with University of Zurich, Switzerland, BriaCell is testing other drugs/product candidates that are expected to boost the effectiveness of Bria-IMT™ and Bria-OTS™.
Ongoing work in the small molecule program to select protein kinase C delta inhibitors for cancer and fibrotic diseases is also progressing according to our timelines. The medicinal chemistry work is being performed at Colorado State University where the current library of compounds available is being augmented.
BriaCell is an immuno-oncology focused biotechnology company developing a targeted and safe approach to the management of cancer. Immunotherapy has come to the forefront of the fight against cancer, harnessing the body’s own immune system in recognizing and selectively destroying cancer cells while sparing normal ones. Immunotherapy, in addition to generally being more targeted and less toxic than commonly used types of chemotherapy, is also thought to be a potent approach with the potential to prevent cancer recurrence.
Bria-IMT™ (SV-BR-1-GM), the Company’s lead product candidate, is derived from a breast cancer cell line genetically engineered to release granulocyte-macrophage colony-stimulating factor (GM-CSF), a substance that activates the immune system by allowing the body to recognize and eliminate cancerous cells by inducing tumor-directed T cell and potentially antibody responses.
The results of two previous proof-of-concept clinical trials (one with the precursor cell line not genetically engineered to produce GM-CSF and one with Bria-IMT™) produced encouraging results in patients with advanced breast cancer. Most notably, one patient with metastatic breast cancer responded to Bria-IMT™ with substantial reduction in tumor burden including breast, lung, soft tissue and brain metastases. The company is currently conducting a Phase I/IIa clinical trial for Bria-IMT™ in patients with advanced breast cancer. This trial is listed in ClinicalTrials.gov as NCT03066947. The trial is being conducted along with the co-development of BriaDX™, the Company’s companion diagnostic test. The interim data for the first 10 patients is expected by the first quarter of 2018. Additionally, the FDA recently approved the roll-over combination study of Bria-IMT™ with pembrolizumab [Keytruda; manufactured by Merck & Co., Inc.] or ipilimumab [Yervoy; manufactured by Bristol-Myers Squibb Company] for patients previously treated with Bria-IMT™ in the Company’s ongoing Phase I/IIa clinical trial in advanced breast cancer. The roll-over trial is listed in ClinicalTrials.gov as NCT03328026.
BriaCell is also developing Bria-OTS™, an off-the-shelf personalized Immunotherapy. Bria-OTS™ consists of 14 individually pre-manufactured genetic alleles. BriaCell’s BriaDX™ companion diagnostic reveals a patient’s specific HLA-types and the 2 best matching alleles are administered to the patient. BriaCell’s 14 alleles (8 Class I and 6 Class II) cover approximately 90% of the Breast Cancer population while eliminating the complex manufacturing logistics required for other personalized immunotherapies. Bria-OTS™ is a personalized therapy without the need for personalized manufacturing.
BriaCell is also developing novel, selective protein kinase C delta (PKCδ) inhibitors. PKCδ inhibitors have shown activity in a number of pre-clinical models of RAS genes’ transformed cancers including breast, pancreatic, non-small cell lung cancer and neuroendocrine tumors (such as carcinoid tumors).
For additional information on BriaCell, please visit our website: http://briacell.com.