Bria-IMT Plus Checkpoint Inhibition Maintains Favorable OS in Metastatic Breast Cancer

Adding the targeted immunotherapy Bria-IMT (SV-BR-1-GM) to either retifanlimab-dlwr (Zynyz) or pembrolizumab (Keytruda) elicited an overall survival benefit among heavily pretreated patients with advanced metastatic breast cancer in a phase 1/2 study (NCT03328026), according to an announcement from BriaCell Therapeutics.¹

Of the 54 patients enrolled onto the study, 37 received the phase 3 formulation of Bria-IMT, 25 of whom were treated when full study activities were resumed in 2022 following the COVID-19 pandemic. After an additional 6 months of follow-up, the median overall survival (OS) among patients treated with the phase 3 formulation since 2022 (n = 25) was 15.6 months and the median progression-free survival (PFS) was 4.1 months. The median number of prior treatment lines in this patient population was 5.5 (range, 2-13). For those treated with the phase 3 formulation since study onset (n = 37), the median OS was 13.4 months and the median PFS was 3.9 months. Patients in this population received a median of 6 prior treatment lines (range, 2-13).

These outcomes compare favorably with OS data for similar patient populations reported in prior literature,¹ and improve upon interim OS data from the combination study presented at the 2023 San Antonio Breast Cancer Symposium, which demonstrated a median OS of 13.4 months among evaluable patients (n = 48).²

“We wanted to look at the phase 2 data of those patients who most closely resemble the patients being treated in our ongoing [phase 3 BRIA-ABC trial (NCT06072612)] and compare them to similar patients in the literature,” Dr William V. Williams, president and chief executive officer of BriaCell, explained in the news release.¹ “The nearly 2-fold OS benefit we are seeing with the Bria-IMT regimen, together with the similar previously reported approximate doubling of PFS compared with literature controls, strongly support our belief that Bria-IMT could have a meaningful impact in the lives of heavily pretreated [patients with] metastatic breast cancer. We look forward to further clinical development of Bria-IMT with the goal of establishing it as a new standard of care for patients with metastatic breast cancer.”

“OS in patients with heavily pretreated metastatic breast cancer is very poor,” Sara A. Hurvitz, MD, professor of medicine at Fred Hutchinson Cancer Center and University of Washington, as well as a medical advisory board member at BriaCell, stated in the news release. “The BriaCell early data [are] quite encouraging from both efficacy and tolerability standpoints.”

Updated efficacy data from the combination study were also presented at the 2024 ASCO Annual Meeting. The 12-week clinical benefit rate (CBR) with Bria-IMT plus a checkpoint inhibitor was 55% across all evaluable breast cancer subtypes (n = 42). The median duration of response was 8.6 months (range, 5.8-9.8) for all patients, and overall response rates in the hormone-receptor–positive, HER2-positive, and triple-negative breast cancer subgroups were 10%, 50%, and 0%, respectively.^3,4

Ongoing Study of Bria-IMT in Breast Cancer

The open-label, phase 1/2 combination study enrolled patients 18 years of age or older with histologically confirmed breast cancer with recurrent and/or metastatic lesions. Patients were required to have persistent disease and local recurrence that was not amenable to local treatment, an expected survival of at least 4 months, and an ECOG performance status of 0 or 1.⁵

Concurrent or recent chemotherapy, immunotherapy, or general anesthesia/major surgery within 21 days; radiotherapy within 14 days of their first dose of study regimen; or toxicity from a previous therapy that had not recovered to grade 1 or less at baseline was not permitted. Patients who had not recovered from adverse effects and/or complications from surgical intervention prior to study treatment were also excluded.

Upon enrollment, patients in the combination cohort received the Bria-IMT regimen, comprising 300 mg/m² of cyclophosphamide administered intravenously 2 days prior to treatment with the 20 x 10⁶ irradiated SV-BR-1-GM cells administered intradermally, followed by interferon-alpha-2b at each inoculation site.⁴

Previously reported data from this study supported the FDA’s decision to grant fast track designation to Bria-IMT for metastatic breast cancer in April 2022, as well as the ongoing evaluation of Bria-IMT plus an immune checkpoint inhibitor in BRIA-ABC.^1,6

“The Bria-IMT regimen is the only investigational drug we have seen to show these impressive survival numbers in heavily pretreated metastatic breast cancer patients who have [progressed on] numerous prior treatments including immune checkpoint inhibitors and antibody-drug conjugates,” Giuseppe Del Priore, MD, MPH, chief medical officer of BriaCell, stated in the news release.¹ “These survival and clinical benefit data support BriaCell’s hypothesis of additive and/or synergistic effects of immune checkpoint inhibitors with Bria-IMT and drive the ongoing pivotal study of our combination regimen in the treatment of [patients with] metastatic breast cancer.”

References

1. Dean F. BriaCell reports positive overall survival (OS) in metastatic breast cancer.News release. BriaCell. September 11, 2024. Accessed September 11, 2024. https://briacell.com/briacell-reports-positive-overall-survival-os-in-metastatic-breast-cancer/
2. Ganegoda C. BriaCell highlights outstanding topline survival and clinical benefit data in advanced metastatic breast cancer at the 2023 SABCS. News Release. BriaCell. December 6, 2023. Accessed September 11, 2024. https://briacell.com/briacell-highlights-outstanding-topline-survival-and-clinical-benefit-data-in-advanced-metastatic-breast-cancer-at-the-2023-sabcs/
3. Ganegoda C. BriaCell doubles progression-free-survival (PFS) and reports clinical benefit data at ASCO 2024. News release. BriaCell. May 24, 2024. Accessed September 11, 2024. https://briacell.com/briacell-doubles-progression-free-survival-pfs-and-reports-clinical-benefit-data-at-asco-2024/
4. Calfa CJ, Nangia CS, Barve MA, et al. Outcomes of advanced/metastatic breast cancer (aMBC) treated with BRIA-IMT, an allogeneic whole cell immunotherapy. J Clin Oncol. 2024;42(suppl 16):1022. doi:10.1200/JCO.2024.42.16_suppl.1022
5. Combination study of SV-BR-1-GM with retifanlimab. ClinicalTrials.gov. Updated October 6, 2023. Accessed September 11, 2024. https://clinicaltrials.gov/ct2/show/NCT03328026
6. BriaCell receives FDA fast track approval for targeted breast cancer immunotherapy. News release. BriaCell. April 13, 2022. September 11, 2024. https://www.globenewswire.com/news-release/2022/04/13/2421857/0/en/BriaCell-Receives-FDA-Fast-Track-Approval-for-Targeted-Breast-Cancer-Immunotherapy.html