Phase 1/2 Trial Testing Combo of Bria-IMT and Immune Checkpoint Inhibitors Begins Dosing Breast Cancer Patients

Phase 1/2 Trial Testing Combo of Bria-IMT and Immune Checkpoint Inhibitors Begins Dosing Breast Cancer Patients

BriaCell Therapeutics has started patient dosing in a Phase 1/2a clinical trial testing its immunotherapy candidate Bria-IMT — used in combination with the immune checkpoint inhibitors Keytruda (pembrolizumab) or Yervoy (ipilimumab) — in advanced breast cancer patients.

Still recruiting participants, the study (NCT03328026) is expected to enroll approximately 40 patients who have failed to respond to prior lines of therapy at five clinical sites across the United States.

Patients whose cancers express the PD-L1 or PD-L2 proteins will receive the Bria-IMT vaccine in combination with the PD-1 inhibitor Keytruda, developed by Merck (known as MSD outside the U.S. and Canada), while those whose cancers are negative for these proteins will receive Bristol-Myers Squibb‘s anti-CTLA4 antibody Yervoy. The combination treatment will be given every three weeks.

“We believe that combination of Bria-IMT with immune checkpoint inhibitors should create even more potent anti-cancer immune responses, leading to our strategy of combination studies of Bria-IMT with Keytruda or Yervoy,” Bill Williams, MD, PhD, president and CEO of BriaCell, said in a press release.

Bria-IMT, formerly known as BriaVax or SV-BR-1-GM, is a vaccine that consists of injections of cells that have been genetically modified to release granulocyte/macrophage-colony stimulating factor (GM-CSF) — an immune system activator.

Patients receiving the cell vaccine are pre-treated with the immunosuppressant cyclophosphamide. Then, two and four days after the Bria-IMT injection, patients are injected with interferon-alpha 2b into each inoculation site to provide an additional “danger signal” that activates the immune system.

The trial’s main goal is to determine if the combinations have an acceptable safety profile. Tumor responses, duration of response, and quality of life will also be assessed as secondary measures.

After enrolling the first six patients, the U.S. Food and Drug Administration requires that a safety analysis be performed before including any more patients. Preliminary safety results are expected by the end of the year, and efficacy data is anticipated by the first quarter of 2019, BriaCell reported.

“We are very excited to test this novel combination treatment approach which we believe will offer significant clinical benefit to patients with advanced breast cancer,” Williams said.

In an ongoing Phase 1/2a trial (NCT03066947) testing Bria-IMT as a single agent in metastatic or recurrent breast cancer patients, the treatment was found to be safe and well tolerated. In addition, it shrank the tumors of 50% of patients who matched with Bria-IMT at two or more human leukocyte antigen (HLA) types — a measure of compatibility. For those with at least one HLA match, the response rate was 27%.

Additionally, 75% and 33% of these patients experienced a reduction in circulating cancer cells.

Further analysis also showed that cancer cells and cancer-associated cells produced the PD-L1 factor in all patients. This provided a strong rationale for combining Bria-IMT with immune checkpoint inhibitors, which don’t seem to work on their own in breast cancer.

“BriaCell is committed to exploring additional ways to address the unmet needs of the advanced breast cancer community,” Williams said.