Abstract PS1-13-22: Impact of Prior Therapy, Genotype Matching, and Biomarkers in the Bria-ABC Phase 3 Trial

Abstract Background Bria-IMT™ is an allogenic whole cell vaccine engineered to express tumor associated antigens and GM-CSF, promoting both adaptive and innate immune responses. The ongoing Bria-ABC trial (NCT06072612) is a multicenter, phase 3 study comparing Bria-IMT based regimens to treatment of physician’s choice (TPC) in pts with late stage metastatic breast cancer who have no conventional options. We explored the feasibility of Bria-IMT in this exceptionally heavily pretreated pt cohort. Methods Pivotal randomized registration trial of Bria-IMT +CPI, Bria-IMT monotherapy, or TPC. Pts randomization 1:1:1 completed; future pts randomized 1:1 into either Bria-IMT + CPI or TPC. The Bria-IMT regimen includes Day -2 cyclophosphamide (300 mg/m2), Day 0 intradermal SV-BR-1-GM (20x106 irradiated cells), and Day 2 pegylated α interferon (0.1 mcg/site). CPI is administered each cycle, q3w. Imaging assessments q6wk (×2) then q8wk. Pts with ECOG < 2, prior checkpoint inhibitor (CPI), antibody drug conjugate (ADC), CDK4/6 inhibitor (CDK4/6i) exposure, and CNS metastases are eligible; no limit on prior lines. This arm blind analysis was conducted to evaluate feasibility, and provide benchmark PFS stratified by prior treatment regimens, HLA alleles, and biomarkers using KM curves, with significance assessed by log rank or Gehan Breslow Wilcoxon tests. Results At data cut off, 186 pts have been screened, 113 randomized, and 107 treated: median age - 59 (range 32-91); BMI -25.1; 75% Caucasian; 20% other; 5% not yet reported; median 6 prior lines (2-15); ECOG 2: 7%, intracranial mets: 11%. 43% of pts HR+, 35% TNBC, 12% HER2+, 7% HER2low and 3% no subtype yet recorded. Among treated pts (n = 107), median PFS (mPFS): 2.9 mo (95% CI, 2.4 - 3.7). mPFS in pts w/ vs. w/o prior ADC; 3.1 vs 6.0 mo(HR: 1.8, 95%CI 0.9-3.6; p=0.09). mPFS in pts w/ vs w/o prior CPI ; 2.3 vs 3.8 mo(HR: 1.8; 95% CI 0.9 - 3.3, p =0.07). Pts w/ vs w/o prior CDK4/6i, mPFS was 3.8 vs 2.1 (HR: 0.5; 95% CI 0.3 - 0.9, p = .03). In treated pts w/ available genotyping (n = 89), those with HLA Class I A2 expression (44%) had a non statistically significant but numerically greater difference in mPFS vs pts expressing other HLA alleles (HR: 1.0; 95% CI 0.6 - 1.7, p = NS). Arm specific HLA based results unreported. Pts w/o detectable CTCs at baseline or follow up, and with a reduction in mean cancer associated macrophage like cell (CAML) size at follow up (n = 22), had a median PFS of 3.8 mo vs 2.3 mo in pts with CTCs present at baseline or follow-up (n = 22) (HR 2.3; 95% CI, 1.1-4.6; p = 0.04). Pts with a disease history of, or emergent, intracranial metastases showed a mPFS of 2.4 vs 3.1 mo in the overall cohort (HR: 1.7; 95% CI 0.7-3.8, p = 0.23). Pts with a favorable neutrophil to lymphocyte ratio (NLR) (≥ 0.7 or ≤ 2.3) after 1st treatment had a mPFS of 4.5 mo vs 2.5 in pts with an unfavorable NLR (< 0.7 or > 2.3) (HR: 0.5; 95% 0.3 - 0.9, p = 0.009). At baseline, favorable NLR mPFS 4.9mo vs 2.8 unfavorable (HR: 0.47; 95% CI 0.3 - 0.8, p = 0.004). No treatment discontinuations or dose reductions related to SV-BR-1-GM reported. Majority of adverse events (76%) were grade 1-2, with few (37%) cases > grade 3, including anemia (6.5%), increased GGT (3.7%), and neutropenia (3.7%). Patients demonstrated stable functional status, as assessed by physical functioning domain questions of the EORTC QLQ-C30. Discussion These preliminary findings from the Bria-ABC Phase 3 trial suggest that early sub-group response trends confirm biomarker utility and feasibility as seen in the phase 2 study supporting continued exploration of Bria-IMT™ even in very advanced MBC. Patients in this late stage, phase III trial maintained functional status w/o evidence of decline. This early prospective RCT in late stage metastatic breast cancer following recent drug approvals offers an emerging benchmark with results that may inform future trial design and guide care for pts who have exhausted standard options. Citation Format: R. Shatsky, K. McCann, A. Kahn, L. Negret, C. Vaughn, B. Bayer, T. Aghajanian, W. Williams, G. Del Priore, C. Nangia. Impact of Prior Therapy, Genotype Matching, and Biomarkers in the Bria-ABC Phase 3 Trial [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS1-13-22.