Findings from a phase 3 trial highlight regression of central nervous system metastases across all heavily pretreated breast cancer subtypes with Bria-IMT.
Treatment with Bria-IMT produced positive intracranial responses in a small cohort of patients with advanced breast cancer and central nervous system (CNS) metastases, according to a press release from BriaCell Therapeutics on data from the phase 3 BRIA-ABC trial (NCT06072612).1
Investigators reported an improvement in CNS lesions among 71% (n = 5/7) of patients treated with Bria-IMT; these findings support the potential efficacy of the agent when administered as monotherapy or with immune checkpoint inhibitors in patients with CNS metastases. Additionally, CNS metastases appeared to regress across all breast cancer subtypes among previously treated patients. The study cohort consisted of heavily pretreated patients who had disease progression following multiple lines of therapy, including one who progressed on treatment with 2 antibody-drug conjugates.
“We have accumulated positive clinical responses in 5 patients with intracranial metastases, which generally are extremely difficult to treat, and have a very poor prognosis,” William V. Williams, MD, FACP, president and chief executive officer at BriaCell, said in the press release. “This antitumor activity furthers our excitement in our ongoing phase 3 pivotal trial studying the Bria-IMT regimen in advanced breast cancer.”
In this open-label phase 3 study, patients were randomly assigned to receive Bria-IMT with or without immune checkpoint inhibitors or control treatment of physician’s choice. In the experimental arms, patients began treatment with cyclophosphamide at 300 mg/m2 followed by Bria-IMT as 4 inoculations and interferon given intradermally into each inoculation site with or without retifanlimab-dlwr (Zynyz) at a total dose of 375 mg. In the comparator arm, patients received carboplatin, taxanes, capecitabine, gemcitabine, vinorelbine, or eribulin.
The trial’s primary end point was overall survival. Secondary end points included progression-free survival, clinical benefit rate, overall response rate, and quality of life.
Patients 18 years and older with histologically confirmed breast cancer harboring locally recurrent unresectable and/or metastatic lesions who have progressed on prior therapy were able to enroll on the trial. Additional eligibility criteria included having a life expectancy of at least 4 months and an ECOG performance status of 0 to 2. Patients with new or progressive brain metastases were able to enroll on the trial if their metastases were clinically stable, did not require management with steroids, and were healed for at least 3 weeks prior to initiation of study treatment if surgically debulked.
Those who received concurrent or recent chemotherapy, immunotherapy, or major surgery within 3 weeks of study entry or radiotherapy within 2 weeks of beginning treatment were not eligible to enroll on the trial. Patients were also unsuitable for enrollment if they had New York Association stage III or IV cardiac disease, a pericardial effusion of moderate severity or higher, symptomatic pleural effusion or ascites, or active infections requiring management with systemic therapy within 30 days of study entry.
The FDA previously granted fast track designation to Bria-IMT as a therapy for metastatic breast cancer in April 2022.2 Supporting data for the designation came from a phase 1/2 study (NCT03328026) assessing Bria-IMT in combination with retifanlimab among patients with metastatic or locally recurrent breast cancer.
“The CNS tumor reductions demonstrated in 5 of 7 [patients with] advanced breast cancer are particularly compelling given the history of unsuccessful treatment of CNS metastases in this patient population,” Giuseppe Del Priore, MD, MPH, chief medical officer at BriaCell, concluded.1