Pivotal Bria-IMT Trial Hopes to Support BLA for Advanced Metastatic Breast Cancer
BriaCell initiated the pivotal phase 3 BRIA-ABC trial in October 2023.
Sara A. Hurvitz, MD
Credit: Fred Hutch
Bria-IMT (SV-BR-1-GM; BriaCell) is an allogeneic, genetically engineered human breast cancer cell line with features of immune cells being investigated as a targeted immunotherapy in patients with advanced metastatic breast cancer. It is designed to both indirectly and directly stimulate innate antitumor activity, via vaccination-like activity and direct stimulation.
Bria-IMT is being evaluated in the pivotal BRIA-ABC phase 3 trial (NCT06072612) in combination with an immune check point inhibitor as compared with physician’s choice of treatment (standard of care; SOC). The trial was initiated in October 2023.1
“Timely initiation of our pivotal study is a key milestone for us further confirming our expedited timeline for FDA approval of our immunotherapy,” William V. Williams, president and chief executive officer, BriaCell, said in a statement.1 “Based on our recently announced benchmark beating survival data, we strongly believe that our novel immunotherapy may transform the way we treat advanced metastatic breast cancer patients, and we look forward to sharing additional development milestones in the coming months.”
The study will enroll 177 patients in the Bria-IMT combination therapy arm, 177 patients in the SOC arm, and 50 patients in a Bria-IMT regimen alone arm (to be eligible for combination therapy after initial post treatment evaluation). The study’s primary endpoint is improvement in overall survival in the combo arm compared with the SOC arm. Secondary endpoints include progression-free survival (PFS), clinical benefit rate (CBR), overall response rate (ORR), quality of life, and event-free survival.1
Participants must be adults with histologically confirmed breast cancer with either locally recurrent unresectable or metastatic lesions that has failed prior approved therapies. Patients with local recurrent disease must not be suitable for local treatment, while those with metastatic disease must lack meaningful alternative therapies. Specific treatment histories are required based on cancer type: HER2 positive disease must have been treated with at least 3 regimens including 2 anti-HER2 and 1 chemotherapy regimen; ER/PR positive tumors must be refractory to at least 2 hormonal agents; triple-negative tumors must have exhausted all curative therapies including 2 chemotherapy regimens; cancers with actionable targets must have received all indicated treatments; HER2 low disease must have received at least 1 HER2-targeted agent in addition to appropriate therapies; HER2 negative tumors must be refractory to hormonal therapy (if indicated) and treated with at least 2 chemotherapy regimens. Patients with brain metastases are eligible if their metastases are clinically stable, not requiring steroids for at least 2 weeks, not impinging on critical brain areas, surgically healed for at least 3 weeks, and have an expected survival of at least 4 months. Finally, participants must have an ECOG performance status of 0, 1, or 2.
Participants are ineligible if they have undergone chemotherapy, immunotherapy, or major surgery within 21 days prior to the first dose, or radiotherapy within 14 days. Unresolved toxicity from prior therapies (excluding grade 1 or baseline alopecia and anemia not requiring transfusion) also disqualifies participants. Significant toxicity from prior checkpoint inhibitors or hypersensitivity to the proposed therapy or its components, as well as certain severe laboratory abnormalities are exclusionary. Additional disqualifications include proteinuria, significant cardiac conditions, pericardial effusion, symptomatic pleural effusion or ascites, and abnormal ECG findings. Participants must not be pregnant or nursing and must take precautions to prevent pregnancy during the study. Active or recent malignancies, uncontrolled HIV/AIDS, immunodeficiency, chronic systemic steroid use, active autoimmune diseases requiring treatment, or active infections also preclude participation. Lastly, those with severe psychiatric conditions, recent live vaccine recipients, or involvement in another clinical trial without approval are excluded.
BriaCell recently presented data on Bria-IMT from an ongoing phase 2 trial (NCT03328026) in 42 evaluable patients at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting taking place held on May 31 - June 4, 2024.
The data demonstrated a median PFS of 4.1 months in patients with heavily pretreated, antibody drug conjugate (ADC)-resistant disease and an overall PFS of 3.9 months, which is double the PFS in similar studies of patients who received physician’s treatment of choice. ORR was 9.5% and CBR was 55% in evaluable patients, which also compares favorably with the literature. Five of 6 treated evaluable patients with intracranial lesions responded. No participants discontinued from the study due to reasons related to Bria-IMT and there were no reports of interstitial lung disease.2
“Patients with heavily pretreated metastatic breast cancer that have developed resistance to ADC face a very poor prognosis. Novel, well tolerated and effective treatments remain a critical need,” Sara A. Hurvitz, MD, Professor of Medicine, Fred Hutchinson Cancer Center and University of Washington, and medical advisory board member, BriaCell, said in an earlier statement.2 “Early data from the BriaCell study are quite promising and if confirmed in the larger clinical trial could be a game changer for patients.”
