DiPriore, Giuseppe

e15060 Background: In metastatic Breast Cancer (mBC) Circulating Tumor Cells (CTCs) are an established prognostic indicator of patients (pts) with highly aggressive disease, poor clinical outcomes, and poor response rates to therapy. However, CTCs are typically found in < 20% of mBC pts and many pts without CTCs also progress. Cancer associated macrophage-like cells (CAMLs) are inflammatory tumor macrophages also found in blood, in > 90% of mBC, and are indicators of poor clinical outcomes independent of CTCs. We conducted a prospective study to model CTC & CAML subtypes from 212 mBC pt blood samples prior to induction of new systemic therapies to optimize and validate risk models based on 2-year outcomes of Progression-free survival (PFS) & Overall survival (OS). Methods: An observational multi-institutional prospective study was conducted on 212 mBC pts prior to induction of a new line of therapy who were progressing on their current therapy. Anonymized (7.5ml) whole blood samples were taken prior to therapy induction and filtered by CellSieve filtration. Quantities and subtypes of CTCs & CAMLs were categorized by their expression of CK+/CD45+/CD14+ for CAMLs and CK+/CD45-/CD14- for CTCs. PFS (RECIST v1.1) and OS hazard ratios (HRs) were calculated by censored univariate & multivariate analysis at 2 years. Results: Pt median age was 51 years (range 25-92); TNBC (44%), ER/PR+ (30%), HER2+ (15%). Pts were treated with chemotherapy alone (18%), immune checkpoint inhibitor (46%), targeted (40%), hormone (8%) and unknown (5%). 38% (81/212) pts had ≥1 CTCs which correlated with significantly poorer PFS (HR = 1.9; 95%CI 1.3-2.7; p = 0.0016) and OS (HR = 2.0; 95%CI, 1.3-3.0; p = 00025), with the most significant risk at ≥8 CTCs (14% pts), PFS (HR = 3.8; 95%CI, 2.1-6.9; p < 0.0001) and OS (HR = 7.2; 95% CI, 3.4-14.9; p < 0.0001). Independently, 93% (n = 196/212) of pts had ≥1 CAML, with a threshold of >40um size (84% pts) had significantly poorer PFS (HR = 2.0; 95% CI, 1.2-3.1; p = 0.0032), but not OS (HR = 1.5; 95%CI, 0.9-2.7; p = 0.1169). However, a threshold of >125um size CAML (43% pts) also had significantly poorer PFS (HR = 1.8; 95% CI, 1.2-2.7; p = 0.0013) and OS (HR = 1.6; 95% CI, 1.0-2.5; p = 0.0233). By combining models, the best outcomes were seen in pts with 0 CTCs & 0 CAMLs (mPFS = 12.6 & mOS = 21.3), followed by 0 CTCs & ≥40um CAMLs (mPFS = 5.2 & mOS = 17.5) and 0 CTCs & ≥125um CAMLs (mPFS = 4.9 & mOS = 15.2). Poorer outcomes were seen with ≥1 CTCs (mPFS = 3.3 & mOS = 13.5) and the worst outcomes with ≥8 CTCs (mPFS = 2.5 & mOS = 4.8). Conclusions: CTCs were uncommon in mBC pts but correlated with very poor clinical outcomes. In parallel analysis, CAMLs were common with CAML size correlating with increasingly poorer outcomes. By combining CTC & CAML subtypes, mBC pts were more accurately stratified by risk of progression and death. Additional multivariate studies correlating treatment class and tumor response rates are ongoing.

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 .