Survival with Bria-IMT + CPI in advanced metastatic breast cancer at 12 and 24 months.

Abstract

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 .