The objective of this study is to evaluate the safety, feasibility, and preliminary antitumor activity of this multi-component immunotherapy strategy in patients with advanced solid tumors. The study is designed to assess whether coordinated enhancement of antigen-specific T-cell priming and tumor microenvironment modulation can improve immune-mediated tumor control.
In this study, BreakVax with adjuvants (Montanide and Poly-ICLC) is administered in combination with:
1. Low-dose subcutaneous ipilimumab at the injection site as a dendritic cell adjuvant to enhance local dendritic cell-mediated T-cell priming; 2. Pembrolizumab to mitigate PD-1-mediated T-cell exhaustion and sustain effector function; 3. Standard-of-care chemotherapy, which may promote immunogenic cell death, increase antigen release and modulate the tumor microenvironment; and 4. Losartan and aspirin, which have been associated in preclinical and translational studies with modulation of stromal architecture, vascular normalization, and reduction of tumor-associated immunosuppressive signaling.
This is a Phase 1/2, multi-center, open-label single-arm clinical study in adult patients who have Glioblastoma (GBM).
The study consists of two components: a Safety Lead-in Cohort and a combination therapy cohort. The Safety Lead-in Cohort is designed to evaluate safety and tolerability of the study combination and to characterize dose-limiting toxicities (DLTs). The combination therapy cohort portion intends to evaluate the superiority of the study combination treatment vs the SOC chemotherapy, measured by OS at 12 months
Age ≥ 18 years and < 72
Patients with histologically confirmed GBM who have sent 200 mg (approximately) of tumor tissue (fresh tissue immersed in AllProtect then frozen) to BreakBio for analysis.
KPS of 80 or greater on day of first dose
Neutrophil to Lymphocyte Ratio (NLR)1 at a healthy adult's normal level: ≤ 3.5
Prior exposure to anti PD- 1/PD-L1 agents.
Prior exposure to immunosuppressive therapy within the last 12 months prior to enrollment.
Receiving or previously receiving oral or IV steroids within 6 weeks of starting study treatment. Currently using or previously used topical steroids within 6 weeks of starting study treatment. Expected to require steroid-containing pre-meds before chemotherapy doses.
Patients with deficient mismatch repair (dMMR) or microsatellite instability (MSI-H) phenotype
BreakBio Corp
Lead sponsor
Miami Cancer Institute
Collaborator