Bria-IMT Cancer Vaccine Shows Efficacy, Tolerability in Advanced Breast Cancer

A phase 1/2 study showed that treatment with cyclophosphamide, SV-BR-1-GM, and retifanlimab yields favorable survival data in heavily pretreated patients with breast cancer.

Low-dose cyclophosphamide followed by the SV-BR-1-GM regimen and retifanlimab-dlwr (Zynyz), then low-dose local pegylated interferon (IFN)-α demonstrated an acceptable tolerability profile and positive clinical benefit, including prolonged overall survival (OS), in heavily pretreated patients with metastatic breast cancer, according to results from an open-label phase 1/2 study (NCT03328026) presented at the 2024 San Antonio Breast Cancer Symposium (SABCS).¹

In patients who received retifanlimab during cycle 1, the OS was undefined (range, 2.73-17.33) compared with 7.23 months (range, 2.43-12.63) in patients who were delayed to receive retifanlimab at cycle 2 (HR, 0.53; 95% CI, 0.22-1.27; P = .15).

For all patients (n = 54), those who received the treatment formulation with IFN-γ, the median OS was 6.93 months (range, 1.83-17.33) and 13.43 months (range, 1.93-30.33) in patients without IFN-γ (HR, 0.37; 95% CI, 0.16-0.86; P = .02).

In the randomized cohort, OS for patients who received the treatment with IFN-γ was 9.1 months (range, 5.47-17.33) and undefined (range, 2.43-16.13) for patients who received the treatment without IFN-γ.

Specifically, regarding patients with intracranial metastasis (n = 8), the median OS was 13.7 months, the median number of prior lines of therapy was 5, the median number of prior lines of radiation was 3, and the median number of prior surgeries was 2.

“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,” lead study author Saranya Chumsri, MD, an oncologist at Mayo Clinic Comprehensive Cancer Center, and coinvestigators wrote in the poster. “These findings will inform the ongoing development for optimized outcomes in future studies.”

Fifty-four patients with a median age of 61 years (range, 38-81) were enrolled in the study. The median number of prior lines of treatment was 6 (range, 2-13); 23 patients (44%) received an antibody-drug conjugate, 11 (20%) had immune checkpoint therapy, and 34 (63%) had a CDK4/6 inhibitor.

Also, 30 patients (56%) had grade 3 tumors, 15 (28%) had grade 2 tumors, and 6 (11%) had grade 1 tumors. Twenty-nine patients (54%) had an ECOG performance status of 0.

The treatment protocol comprised 300 mg/m² of intravenous cyclophosphamide given 48 hours before approximately 20 million cells of irradiated SV-BR-1-GM given intradermally, then 0.1 mcg of pegylated IFNα at every inoculation site 2 days afterward.

Patients were randomized 1:1 to receive retifanlimab or pembrolizumab (Keytruda) immediately at cycle 1 or later during cycle 2. There were also 2 different formulations of SV-BR-1-GM, 1 with IFN-γ pre-treatment and 1 without IFN-γ pre-treatment.

During cycle 1, a Candida skin test is performed to evaluate anergy. An SV-BR-1-GM delayed-type hypersensitivity skin test is done by intradermal injection of a test dose of SV-BR-1-GM at every cycle prior to full dose of SV-BR-1-GM inoculation.

The primary end points were safety, the proportion of patients with abnormalities in safety laboratory parameters, and changes in the electrocardiogram QT interval.² Secondary end points include ORR, duration of response, complete response, partial response, and stable disease.

Overall, the objective response rate (ORR) and clinical benefit rate (CBR) were 10% and 50%. In patients with HER2-positive breast cancer, they were 50% and 100%, for patients with hormone receptor–positive and HER2-negative breast cancer they were 10% and 62%. For patients with triple-negative breast cancer, these rates were 0% and 36%, respectively.

Regarding safety, the most common adverse events (AEs) of any grade were injection site reaction (31.5%), fatigue (22.0%), nausea (14.8%), and anemia (14.8%). Of AEs grade 3 or higher, fatigue (5.6%) and anemia (5.6%) were the most common.

References

1. Chumsri S, Nangia C, Barve M, et al. Overall survival results of BRIA-IMT allogenic whole cell-based cancer vaccine. Presented at: 2024 San Antonio Breast Cancer Symposium; December 10-13, 2024; San Antonio, TX. Abstract PS3-04.
2. Combination study of SV-BR-1-GM with retifanlimab. ClinicalTrials.gov. Updated October 6, 2023. Accessed December 23, 2024. https://tinyurl.com/3cmp25cp