Monitoring blood-based biomarkers as early predictors of progression-free survival in a randomized Bria-ABC phase 3 trial for advanced metastatic breast cancer: An ongoing analysis.

2652 Background: Circulating Tumor Cells (CTCs) are prognostic for poor outcomes in metastatic Breast Cancer (mBC), however CTCs are uncommon in mBC (<20%) and many pts without CTCs often progress. Cancer associated macrophage-like cells (CAML) are prognostic inflammatory pro-tumorigenic PD-L1 expressing macrophages common in mBC pt blood (>90%). In a previous randomized phase II trial, CTC & CAML decreases post Bria-IMT induction correlated with clinical benefit. Bria-IMT is an allogenic whole cell vaccine engineered to express tumor associated antigens & GM-CSF, promoting adaptive & innate immune responses. The ongoing Bria-ABC (NCT06072612) phase 3 study compares Bria-IMT to physician’s choice (TPC) in late stage mBC. We present interim results, without treatment arm comparison, for Progression Free Survival (PFS) by CTC & CAML changes as the exploratory part of the trial. Methods: This still blinded ongoing multicenter randomized open label Phase 3 trial evaluates Bria-IMT+ checkpoint inhibitor (CPI) vs TPC in mBC pts lacking approved therapies. Pts are randomized 1:1:1 to Bria-IMT+CPI, TPC, or Bria-IMT monotherapy (discontinued after 150 pts). The Bria-IMT consists of cyclophosphamide, irradiated SV-BR-1-GM cells, micro-dose pegylated α IFN at each inoculation site. CPI is administered day -3 to 3. TPC followed standard of care. Blinded anonymized blood was taken at baseline (BL), prior to therapy & 2nd (T1) taken at cycle 3 (~4 weeks post initiation). CTCs & CAMLs, and PD-L1 expressions, were quantified using LifeTracDx liquid biopsy with analysis of PFS by censored univariate analysis. Results: At time of analysis, >250 consented, >170 randomized, 119 had BL and 78 had T1. Median age 56 yrs [34–83], median 6 [2–13] prior lines of therapy, 31% TNBC, 62% ER+/PR+, & 15% HER2+. ≥1 CTCs were found in 25% (30/119) at BL & 22% (17/78) at T1. ≥1 CAMLs were found in 93% (111/119) at BL & 95% (74/78) at T1. At BL, ≥1 CTC was not significant for PFS (HR=1.7, CI95% 1.0-2.9, p=0.0513), but ≥2 CTCs was significant for worse PFS (HR=1.8 CI95% 1.1-3.1, p=0.0480). At T1, ≥1 CTCs nor ≥2 CTCs correlated with PFS (HR=0.9, p=0.8392) & (HR=1.6, p=0.1079), respectively. Further, a decrease in CTCs was seen in 11 pts but did not correlate with PFS (HR=0.7, p=0.6552). ≥1 CAML at BL nor T1 correlated with PFS (HR=1.2 CI95% 0.7-2.0, p=0.6811) or (HR=0.9 CI95% 0.7-2.5, p=0.5307), respectively. However, 51 pts (65%) had a decrease or stable CAML counts between BL & T1 which did significantly correlate with better PFS (HR=2.2 CI95% 1.2-3.9, p=0.0154). Conclusions: In an ongoing analysis of a heavily treated mBC pts, we observed that in the entire blinded population, 65% of pts had stability/drop in CAMLs significantly correlated with better PFS. Treatment arm specific comparisons will not be unblinded until completion of the designated milestone (144 mortalities). Clinical trial information: NCT06072612 .