Abstract
Background: Despite advances in metastatic breast cancer (MBC), patients encounter challenges from resistance or intolerance. Bria-IMT is a combination immunotherapy using an allogeneic whole-cell cancer vaccine (SV-BR-1-GM) combined with checkpoint inhibitors (CPIs). Irradiated SV-BR-1-GM breast cancer cells, engineered to secrete GM-CSF, present tumor-associated antigens on HLA-I and HLA-II molecules, directly stimulating anti-tumor immunity. The addition of anti-PD1 CPI further potentiates the activity of SV-BR-1-GM to overcome the immune-suppressive tumor microenvironment. Methods This phase I/II study evaluated the Bria-IMT regimen consisting of low-dose cyclophosphamide (Day –2) followed by SV-BR-1-GM and CPI (pembrolizumab or retifanlimab), then low-dose local peg- interferon α, all given every 3 wks. In the phase II study, patients were randomized 1:1 to start CPI immediately at cycle 1 or delayed start at cycle 2. There were 2 formulations of SV-BR-1-GM with or without IFNγ incubation. Cancer-associated macrophage-like cells (CAMLs), circulating tumor cells (CTCs), and PD-L1 expression scores on these cells were monitored as biomarkers. A Candida skin test assessed anergy status before cycle 1, while a delayed-type hypersensitivity (DTH) skin test was done at each cycle with a small SV-BR-1-GM dose before the full dose. Results A total of 54 patients were enrolled with 22 patients in phase I and 32 in phase II. 11 patients were treated with pembrolizumab and 44 patients with retifanlimab (1 patient received pembrolizumab and later retifanlimab). Median age was 61 (38-81) years; median prior regimen was 6 (2-13). 39(72%) patients were ER+/PR+/HER2-; 3(6%) HER2+, and 12 (22%) triple-negative (TNBC). The Bria-IMT regimen was well tolerated, with no drop-outs attributable to Bria-IMT. The majority of adverse events (67%) were grade 1-2, with few (13%) cases > grade 3, including pulmonary embolism, dehydration, and increased lipase. In the entire cohort, the median overall survival (OS) was 9.9 (1.8-28.5) months. Patients who received the SV-BR-1-GM phase 3 formulation (without IFNγ incubation) (n=37) had a significant increase in both PFS (3.6 vs 2.6 months, P 0.01) and OS (13.4 vs. 6.9 months, P 0.04), an objective response rate (ORR) of 9.5% and a clinical benefit rate (CBR) was 55%. Among randomized patients receiving phase 3 formulation (n=21) median OS not yet reached. In ER+/PR+/HER2-, OS was 13.3 (1.8-28.5) months, HER2+ 11.9 (7.2-11.9) months, and TNBC 8.5 (2.1-15.6) months. There was a significant difference in PFS but not OS among patients who received immediate vs. delayed start of CPI (PFS 3.6 vs. 2.6 months, P 0.02; OS 9.9 vs. 11.9 months, P 0.45). Among 36 patients with post-dose CAML/CTC data, patients with post-dose CTC count < 5 had a significantly improved OS compared with a CTC count > 5 (13.4 vs. 5.5 months, P 0.01). Patients with positive DTH had significantly improved PFS (3.5 vs. 2.4 months, P 0.001) and OS (11.9 vs. 5.5 months, P 0.002). Conclusions: In heavily pretreated MBC patients, the Bria-IMT regimen demonstrated promising results across all subtypes of breast cancer with favorable safety profiles. There was no significant difference in OS among patients treated with immediate vs. delayed CPI. However, superior outcomes were observed in patients receiving SV-BR-1-GM without IFNγ incubation. This formulation has advanced into the ongoing clinical trials. Patients with post-dose CTC count < 5, and positive DTH had significantly improved outcomes. Based on these promising findings, the randomized phase III trial comparing the BRIA-IMT regimen to the treating physician's choice is currently ongoing (NCT06072612). Trial information: NCT03328026.
Citation Format: Saranya Chumsri, Chaitali Nangia, Minal Barve, Kendrith Rowland, Ralph Boccia, John George Knecht, Blaise Bayer, Marcela Salgado, Tamar Aghajanian, William Williams, Charles Wiseman, Giuseppe Del Priore, Carmen Calfa. Overall Survival Results of Bria-IMT Allogenic Whole Cell-Based Cancer Vaccine [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr PS3-04.