The combination of cyclophosphamide, SV-BR-1-GM vaccine, and retifanlimab-dlwr (Zynyz) has demonstrated promising efficacy and tolerability in patients with advanced breast cancer, according to new clinical trial results presented at the 2024 San Antonio Breast Cancer Symposium.
Patients receiving retifanlimab during the first treatment cycle showed notably improved survival outcomes compared to those who started the immunotherapy agent in cycle 2. The study revealed undefined overall survival (ranging from 2.73 to 17.33 months) in early retifanlimab recipients versus 7.23 months (range 2.43-12.63 months) in delayed treatment patients.
Treatment Protocol and Patient Demographics
The study enrolled 54 heavily pretreated patients with a median age of 61 years. Participants had received a median of 6 prior lines of treatment, with 44% having previous exposure to antibody-drug conjugates and 63% to CDK4/6 inhibitors.
The treatment protocol consisted of:
- 300 mg/m2 intravenous cyclophosphamide
- Approximately 20 million cells of irradiated SV-BR-1-GM administered intradermally
- 0.1 mcg pegylated interferon-α at inoculation sites
- Randomized administration of retifanlimab or pembrolizumab
Efficacy Across Different Breast Cancer Subtypes
The treatment showed varying effectiveness across different breast cancer subtypes:
- HER2-positive breast cancer: 50% objective response rate (ORR) and 100% clinical benefit rate (CBR)
- Hormone receptor-positive/HER2-negative: 10% ORR and 62% CBR
- Triple-negative breast cancer: 36% CBR with no objective responses
Particularly noteworthy were the results in patients with intracranial metastases (n=8), who achieved a median overall survival of 13.7 months despite having received a median of 5 prior therapy lines.
Safety Profile
The treatment demonstrated a manageable safety profile with most common adverse events being:
- Injection site reactions (31.5%)
- Fatigue (22.0%)
- Nausea (14.8%)
- Anemia (14.8%)
Grade 3 or higher adverse events were relatively rare, with fatigue and anemia each occurring in 5.6% of patients.
"The Bria-IMT regimen with an immune checkpoint inhibitor appears well tolerated and is capable of producing clinical benefit in heavily pretreated patients with metastatic breast cancer," stated Dr. Saranya Chumsri, lead study author from Mayo Clinic Comprehensive Cancer Center.
The study findings suggest particular promise for patients with HER2-positive disease and those with brain metastases, potentially offering a new treatment option for these challenging patient populations. These results will inform future studies aimed at optimizing treatment outcomes in advanced breast cancer.
