Bria-IMT Plus Checkpoint Inhibition Is Safe and Yields Clinical Benefit in Pretreated Metastatic Breast Cancer

Breast Cancer | Image Credit:

© Sebastian Kaulitzki – stock.adobe.com

Treatment with the off-the-shelf, targeted, cell-based immunotherapy Bria-IMT (SV-BR-1-GM) in combination with an immune checkpoint inhibitor demonstrated favorable safety, tolerability, and evidence of clinical benefit in heavily pretreated patients with metastatic breast cancer, according to findings from an ongoing phase 1/2 trial (NCT03328026) presented at the 2025 AACR Annual Meeting.

Findings showed that in patients treated with Bria-IMT (n = 54), the most common any-grade treatment-related adverse effects (AEs) including injection site reactions (31.5%), fatigue (22%), nausea (14.8%), anemia (14.8%), increased thyroid-stimulating hormone levels (9.3%), fever (9.3%), vomiting (7.4%), constipation (5.6%), hypothyroidism (5.6%), injection-site erythema (5.6%), appetite complications (3.7%, headache (3.7%), rash/ maculopapular rash (3.7%), edema of the limbs, extremities, or anasarca (3.7%), weakness (3.7%), and diarrhea (1.9%). Most AEs were grade 1 or 2 in severity.

Among efficacy evaluable patients in the overall population (n = 42), the overall response rate (ORR) was 10% with a clinical benefit rate of 55%. Among patients with HER2-positive breast cancer (n = 2), those with hormone receptor–positive/HER2-negative breast (n = 29), and those with triple-negative breast cancer (TNBC; n = 11), the respective ORRs were 50%, 10%, and 0%. The CBRs for these populations were 100%, 55%, and 45%, respectively.

Additionally, patients treated with the phase 3 Bria-IMT formulation without interferon-gamma (IFNγ) pre-treatment achieved a median overall survival of 13.43 months (range, 1.9-30.3) compared with 6.93 months (range, 1.8-17.3) for those who received INFγ. No statistically significant differences in OS survival were observed between hormone receptor–positive/HER2-negative and TNBC subgroups, where the median OS was 17.30 months (range, 1.93-30.30) and 11.44 months (range, 2.1-16.00), respectively (HR, 0.49; 95% CI, 0.16-1.56; P = . 23).

“OS among patients treated with the phase 3 formulation remains encouraging and compares favorably [with] historical benchmarks in similar populations,” lead study author Saranya Chumsri, MD, a medical oncologist at the Mayo Clinic in Jacksonville, Florida, and colleagues wrote in a poster presentation of the data. "The Bria-IMT regimen combined with an immune checkpoint inhibitor continues to demonstrate a favorable tolerability profile and evidence of clinical benefit in heavily pretreated patients with metastatic breast cancer."

Phase 1/2 Trial Design

This ongoing, prospective, phase 1/2 trial is evaluating Bria-IMT in combination with an anti–PD-1 checkpoint inhibitor in patients with advanced metastatic breast cancer. The study features a randomized phase 2 cohort initiated in 2018. Eligible patients include those with advanced metastatic breast cancer, and to date, 54 patients have received at least 1 dose of the treatment regimen.

The regimen consists of intravenous cyclophosphamide at 300 mg/m² administered 48 hours prior to inoculation with irradiated SV-BR-1-GM cells at a target of approximately 120 million cells, followed by pegylated interferon-alpha (IFNα) at 0.1 mg administered 2 days after cell injection. A candidate skin test is performed at cycle 1 to assess antigenicity. At each treatment cycle, a delayed-type hypersensitivity (DTH) skin test is conducted using intradermal injection of SV-BR-1-GM cells prior to full dosing.

In the randomized portion, patients started treatment with the checkpoint inhibitor with Bria-IMT during cycle 1 or delayed checkpoint inhibition until cycle 2. Additionally, 2 formulations of SV-BR-1-GM—with and without IFNγ pre-treatment—are being evaluated.

The primary objectives include assessment of safety, tolerability, and immune activation. Secondary analyses are exploring immunologic responses based on DTH testing and preliminary signals of clinical efficacy.

Baseline Patient Characteristics

The study population (n = 54) had a median age of 61 years (range, 38-81) and a median BMI of 28.1 kg/m² (range, 18.1-42.7). The majority of patients were White (78%), followed by Black (11%), Hispanic (6%), Asian (3%), and other racial/ethnic groups (6%). ECOG performance status was evenly distributed, with 54% of patients having a performance status of 0 and 46% with a score of 1.

Tumor grading revealed that 11% of patients had grade 1 disease, 26% had grade 2 disease, and 56% had grade 3 disease; tumor grade was unknown for 8% of patients. Patients had received a median of 6 prior systemic therapies (range, 2-13); patients had prior exposure to antibody-drug conjugates (ADCs; 44%), checkpoint inhibitors (61%), and CDK4/6 inhibitors (63%). Additionally, 22% of patients had 1 HLA match, 74% had 2 or more matches, and 4% had an unknown match status.

Efficacy Analysis Continued

Findings from the randomized portion of the study showed that patients who received an immune checkpoint inhibitor in cycle 1 achieved a median OS of 10.8 months (range, 2.73-17.33) compared with 7.4 months (range, 2.43-18.90) in those who started immune checkpoint inhibition in cycle 2 (HR, 0.57; 95% CI, 0.23-1.44; P = .20). When pooling these 2 groups, the median OS was 9.9 months (range, 2.43-18.90).

Among patients with intracranial lesions and evaluable outcomes (n = 6), the ORR and CBR were 50% and 75%, respectively.

In the broader cohort of patients with at least 1 follow-up tumor assessment (n = 35), 26% experienced a reduction in the sum of target lesion diameters from baseline, and 34% achieved either a decrease or no increase (≤0% change) at their most recent tumor assessment. The maximum observed decrease in lesion diameter was –70%.

Exploratory survival analyses demonstrated patients who had a DTH response experienced a median OS, 13.3 months (range, 2.3-30.3) compared with 4.7 months (range, 1.83-8.60) in patients without a DTH response (HR, 0.02; 95% CI, 0.0004- P < .001). Those with HLA matching had a median OS of 13.4 months (range, 5.8-19.6), and the OS in patients without an HLA match was undefined (P = .04).

Reference

Chumsri S, Nangia C, Barve M, et al. Survival outcomes of Bria-IMT: an allogeneic whole cell cancer vaccine. Presented at: 2025 AACR Annual Meeting; April 25-30, 2025; Chicago, IL. Abstract CT100.