Priore, Giuseppe Del

e14535 Background: Anti-programmed cell death ligand PD-L1/PD-1 immune checkpoint inhibitors (ICIs) are approved for metastatic breast cancer (mBC) patients (pts) with a tumor combined positive score (CPS) ≥10% in their tissue. However, many pts with < 10% CPS may also respond to ICIs. Recent studies in lung cancer have shown that circulating tumor cells (CTCs) and tumor-macrophage fusion cells (TMFCs) both express, and may upregulate, PD-L1 which is predictive for ICI responses. We initiated a prospective study to monitor PD-L1 in CTCs & TMFCs in mBC pts prior to receiving systemic ICIs to correlate their PD-L1 expression to progression free survival (PFS) and overall survival (OS) at 24 months. Methods: We conducted a multi-institutional prospective pilot study of n = 102 pts with pathologically confirmed mBC, having failed ≥1 prior lines of therapy, prior to receiving ICIs (n = 52 Pembrolizumab, n = 39 Retifanlimab, n = 5 Atezolizumab, and n = 1 Nivolumab). Anonymized blinded peripheral blood samples (7.5ml) were procured prior to ICI induction (T0) and (~40 days after ICI induction (T1). TMFCs & CTCs were isolated using Cellsieve microfilters with average PD-L1 expressions measured then categorized as negative/low or high. Tumor CPS was categorized as negative/low (< 10%) or high (> 10%). We compared TMFC PD-L1 to tissue CPS by linear regression. TMFC/CTC PD-L1 expression and tissue PD-L1 CPS were compared to pts’ PFS and OS by Cox proportional univariate and multivariate analysis over 24 months. Results: Of n = 102 pts, median age = 59 years (range 32-77); 42% (43/102) were ER+, 33% (33/102) were PR+, 5% (5/102) were HER2+, and 56% (57/102) were triple-negative. 32% (32/102) had an ECOG score of 0, 25% (26/102) had ECOG 1, and 43% of scores were unavailable. N = 42 pts had available tumor CPS data, which did not correlate to TMFC/CTC PD-L1 at T0 or T1. Pts with high CPS did not significantly predict for PFS (HR = 0.78; 95% CI, 0.3-1.9; P = 0.7627) nor OS (HR = 0.54; 95% CI, 0.2-1.7; P = 0.4471). Pts with high TMFC/CTC PD-L1 at T0 also did not significantly predict for PFS (HR = 0.74; 95% CI, 0.5-1.2; P = 0.2799) nor OS (HR = 0.84; 95% CI, 0.4-1.6; P = 0.7220). However, of the n = 82 pts who provided T1 samples, high CTC/TMFC PD-L1 at T1 was significant for better PFS (HR = 2.55; 95% CI, 1.6-4.2; P = 0.0004) and better OS (HR = 2.06; 95%CI, 1.1-3.8; P = 0.0309). Conclusions: In this study of mBC pts treated with PD-L1 ICIs, tissue CPS did not correlate with PD-L1 expression in CTCs or TMFCs. Further, neither CPS nor baseline PD-L1 in CTC/TMFCs predicted for clinical outcomes in ICI therapies. However, PD-L1 in CTC/TMFCs ~40 days post-induction of ICI did predict for better response rates. While this study suggests predictive value of monitoring PD-L1 in blood during ICI therapies, further studies are required to refine and validate these findings.

1107 Background: Bria-IMT is an allogeneic whole cell immunotherapy expressing tumor associated antigens and GM-CSF to stimulate adaptive and innate immunity. The phase 3 Bria-ABC trial (NCT06072612) evaluates Bria-IMT + retifanlimab vs physician’s choice in MBC w/ no meaningful therapeutic options. Characterization of on-trial pt experience, including quality of life (QOL) and tolerability, remains clinically relevant yet underreported. We evaluated QoL and toxicity to assess feasibility of home self administration. Methods: EORTC QLQ-C30 at baseline (BL) and subsequent visits. Raw item responses were aggregated into domain scores. Changes quantified as absolute point differences; domain scores defined as medians of constituent items. Lower functional/symptom and higher global scores indicate better outcomes. Wilcoxon matched pairs test assessed change from BL. Missing QoL data handled by observed cases approach. QoL evaluated at BL, V3, V6, and V9. TWiST and TOX summarized descriptively. TOX defined as cumulative time w/ grade ≥3 TEAEs w/o progression; TWiST as time w/o grade ≥3 toxicity or progression. TOX and TWiST constitute component health states for planned QTWiST analysis pending mature OS. Results: At submission, 251 pts screened, 173 randomized, 147 treated. 75% Caucasian, 20% other, 5% not reported; median 6 prior lines (2-15); ECOG 2 -6%; intracranial mets 9%; 42% HR+, 37% TNBC, 12% HER2+. Median 5 QoL assessments/pt completed. 127 pts completed ≥2 assessments. Paired data available at V3 52%, V6 17%, V9 6%. Global health medians BL 5.0, V3 5.0, V6 5.0, V9 4.5. Score maintenance/improvement: @V3 63% (p=0.7), V6 62%, V9 71%. Functional domains: role (BL 1.5, V3 2.0, V6 2.0, V9 2.0; maintenance 62.7% [p=0.02], 52.4%, 71.4%). Physical (BL 1.0, V3 2.0, V6 2.0, V9 2.0; maintenance 68.7% (p=0.002), 47.6% (p=0.03), 71.4%), cognitive (BL 1.5, V3 1.5, V6 1.5, V9 1.5; maintenance 63.6%, 61.9%, 85.7%). Emotional (BL 1.5, V3 1.5, V6 1.5, V9 1.5; maintenance 75.8% (p=0.9), 81.0%, 85.7%). Social (BL 1.5, V3 1.5, V6 2.0, V9 2.5; maintenance 58.5%, 75.0%, 57.1%). Symptoms: nausea/vomiting (1.0 throughout; maintenance V3 73%, V6 86%, V9 86%), fatigue median 2.0 all timepoints; maintenance 61%, 67%, 71%), pain (BL/V3 1.5, V6/V9 2.0; maintenance V3 57% [p=0.03], V6 62% [p=0.9], V9 86%). TWiST and TOX restricted mean 3.12 mo and 0.63 mo, respectively; 83.2% and 16.8% of observed follow-up. Pts w global health maintenance demonstrated longer median TWiST v deterioration (4.3 v 2.7 mo). ECOG stable in 78% (n=99). Conclusions: Heavily pretreated MBC pts in Bria-ABC demonstrated stable global health and key functional domains. Findings support sustained QoL in advanced disease. TWiST demonstrates meaningful benefit w/o significant toxicity. Ongoing follow up will further characterize durability of pt-reported outcomes and clinical correlation. Results support decentralized care and potential home self administration. Clinical trial information: NCT06072612 .

1108 Background: Metastatic breast cancer (MBC) remains limited by resistance and cumulative toxicity in heavily pretreated patients. Bria-IMT combines a whole-cell vaccine (SV-BR-1-GM) with anti-PD-1 (CPI) to enhance tumor antigen presentation and overcome immune exhaustion. SV-BR-1-GM is an irradiated breast cancer cell line engineered to secrete GM-CSF, promoting HLA class I and II antigen presentation and T-cell activation. We identified a subset with durable clinical benefit and biologic correlates. Methods: Phase I/II evaluating the Bria-IMT regimen (SV-BR-1-GM with CPI (pembrolizumab or retifanlimab). In the phase II portion, pts were randomized 1:1 to CPI initiation at cycle 1 (C1) or delayed start at cycle 2 (C2). Two SV-BR-1-GM formulations were administered: IFNγ-stimulated (IFγ) or unstimulated (≠IFγ). Baseline circulating tumor cells (CTCs) and delayed-type hypersensitivity (DTH) responses to SV-BR-1-GM were assessed as biomarkers. Progression free survival (PFS) and overall survival (OS) were analyzed using Kaplan Meier (KM). Subgroup comparisons (CPI sequencing, IP formulation, DTH status, and baseline CTC status) are exploratory. Results: 32 phase 2 pts were randomized: median age 61 (range 41-80); median prior lines 6 (range 2-13); PFS 3.5 mo (95% CI 3.0 - 4.2); OS 9.5 mo (95% CI 7.0 - 17.4). Among CPI C1 vs C2 starts: median OS 13.3 v 7.4mo (HR 0.8; 95% CI 0.4-1.9, p = 0.6); OS KM probability at 12 mo 47% v 58%. Median OS w ≠IFγ v IFNγ IP =16.6 v 9.1 mo (HR 0.58; 95% CI 0.2-1.4, p = 0.23); OS KM at 12 mo 52.4% v 27.3%. DTH+ v DTH- median OS 11.9 v 4.7 mo (HR 0.0009; p = <0.001), OS KM @12 mo 48% v 0%. CTCs <5 v > 5 at baseline had median OS 16.6 v 5.5 mo (HR 0.005; 95% CI 0.0003-0.09, p < 0.001), OS at 12 mo 49% vs 33%. Among long term survivors @12mo, OS probability 44.0% (95% CI 26.2-59.7%) and @24 mo 26% (95% CI 12.1-42.4%). Median follow up 25.8 with PFS 5.4 mo. 5 received ≠IFγ formulation v 1 w IFNγ. All 6 (3 with CPI @C1, 3@C2) experienced delayed type hypersensitivity reaction to inoculation. 67% of long responders matched HLA at >1 allele, 33% no match. Grade ≥3 AEs in 47% of pts, most common injection site rxn, nausea, fatigue; no tx related D/C; no unexpected safety signals. Conclusions: In heavily pretreated MBC, Bria-IMT demonstrated a tolerable safety profile and the emergence of a long-term survivor cohort. Durable survival was observed beyond 12 and 24 months. Differential survival favoring Ph3 formulation, DTH positivity, lower baseline CTC burden, and early CPI sequencing was observed. These findings support prospective validation of DTH and CTC as predictive biomarkers and the continued use of the Ph3 IP formulation in the ongoing phase 3 study Bria-ABC (NCT06072612). Clinical trial information: NCT06072612 .

Abstract Background: Bria-IMT™ is an allogeneic whole cell immunotherapy expressing tumor associated antigens and GM-CSF, designed to stimulate adaptive and innate immune responses. The ongoing multicenter phase 3 Bria-ABC trial (NCT06072612) evaluates Bria-IMT + Retifanlimab vs physician’s choice in pts with metastatic breast cancer who have exhausted standard therapies. Quality of life characterization in this advanced disease setting is clinically relevant yet underreported. Methods: QOL was assessed using the European Organization for Research and Treatment of Cancer QOL Questionnaire Core 30 (EORTC QLQ-C30) at baseline (BL) and treatment visits. Raw item responses (scale: 1 - 4 for functional/symptom items; 1 - 7 for global health ; lower scores = better functional/symptom outcomes; higher scores = better global health) were aggregated into domain scores. Changes from BL were quantified as absolute point differences on response scales and domain level scores are the median of constituent items. Changes from BL assessed using Wilcoxon matched-pairs signed-rank tests. ECOG status assessed at BL and each treatment visit. TEAEs graded per CTCAE. Missing QOL data handled using observed cases approach. We report QoL outcomes at visits (V) BL, 3, 6, and 9 to characterize pt experience during treatment. Results: As of data cut date, 235 pts have been screened, 169 randomized,129 treated. Median age: 60. 74% Caucasian; 18% other; 8% not reported; median 6 prior lines (2-15); ECOG 2: 7%, intracranial mets: 11%. 51% of pts HR+, 37% TNBC, 10% HER2+, 2% not reported. mPFS 2.9 mo (95% CI, 2.3 - 3.7), median of 5 QoL assessments per pt. Of 127 pts who completed ≥2 EORTC QLQ-C30 assessments, 67 (52%), 21 (17%), and 7 (6%) had paired data available at V3, 6, and 9, respectively. Global health status remained stable (median: BL 5.0, V3 5.0, V6 5.0, V9 4.5; 63% of pts reported maintenance or improvement at V3 [p=0.7], V6: 62%, V9: 71%). Functional domains: physical (median: BL 1.0, V3 2.0, V6 2.0, V9 2.0; 68.7% , 47.6% [p=0.03], 71.4% maintenance), role (BL 1.5, V3 2.0, V6 2.0, V9 2.0; 62.7% [p=0.02], 52.4%, 71.4% maintenance), emotional (BL 1.5, V3 1.5, V6 1.5, V9 1.5; 75.8% [p=0.9], 81.0%, 85.7% maintenance), cognitive (BL 1.5, V3 1.5, V6 1.5, V9 1.5; 63.6% [p=0.2], 61.9%, 85.7% maintenance), and social functioning (BL 1.5, V3 1.5, V6 2.0, V9 2.5; 58.5% [p=0.06], 75.0%, 57.1% maintenance). Symptoms: fatigue (median 2.0 at all timepoints; 61%, 67%, 71% maintenance), nausea/vomiting (1.0 throughout; 73% maintenance at V3 [p=0.8], V6 86% , V9 86%), and pain (1.5 at BL and V3, increasing to 2.0 at V6 and V9, w/ 57% maintenance at V3 [p=0.03], V6 62% [p=0.9], and V9 86%. ECOG status remained stable in 78% (n = 99) of pts during treatment. Most common TEAEs were fatigue, nausea, anemia, and constipation; w/ 45% Grade 3 or 4; 84% &lt; grade 3. QoL trends consistent w/ observed ECOG status and AE profiles. Conclusion: Heavily pretreated metastatic breast cancer pts demonstrated stability in overall health status and key functional domains during treatment. These findings are encouraging w/ a meaningful QOL in a population with advanced disease and limited therapeutic options. These observations and AE profile support decentralized clinical trial initiatives including home self-administration. Ongoing follow up will further characterize the durability of pt reported outcomes and their relationship w/ clinical status. Citation Format: Saranya Chumsri, Chaitali Nangia, Adriana Kahn, Lawrence Negret, Carmen Calfa, Blaise Bayer, Giuseppe Del Priore, Tamar Aghajanian, William Williams, Kelly McCann. QOL outcomes in Bria-ABC late stage metastatic phase 3 trial [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(8_Suppl):Abstract nr CT137.