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
Single group
BreakVax
DrugAn investigational, personalized peptide-based cancer immunotherapy designed to stimulate patient-specific antitumor T-cell responses. For each patient, tumor tissue undergoes integrated genomic, transcriptomic, and proteomic analysis to identify tumor-associated antigens (TAAs) and tumor-specific neoantigens (TSAs). A proprietary selection algorithm prioritizes peptides predicted to be presented by the patient's HLA molecules and selectively expressed or overexpressed in tumor tissue. The resulting individualized peptide pools are manufactured, formulated with adjuvants (Montanide ISA 51 and Poly-ICLC), and administered subcutaneously
Ipilimumab 2.5 mg
DrugLow-dose subcutaneous ipilimumab at the injection site as a dendritic cell adjuvant to enhance local dendritic cell-mediated T-cell priming
Pembrolizumab
DrugTo mitigate PD-1-mediated T-cell exhaustion and sustain effector function
Temozolomide (TMZ)
DrugMay promote immunogenic cell death, increase antigen release and modulate the tumor microenvironment
Losartan and aspirin
DrugHave been associated in preclinical and translational studies with modulation of stromal architecture, vascular normalization, and reduction of tumor-associated immunosuppressive signaling
Overall Survival (OS)
Percentage of patients for whom BreakVax is successfully manufactured
Adverse events
T-cell infiltration
Change in tumor-infiltrating T-cells between the pre-treatment biopsy and the on-treatment biopsy
Immune-related Objective Response Rate (irORR) per iRANO
Percentage of participants with measurable enhancing disease at baseline who achieve an immune-related complete response or partial response according to iRANO criteria, as assessed by a central independent review committee (IRC).
Progression-Free Survival (PFS) per RANO
Time from the start of study treatment to the first documentation of progressive disease according to RANO criteria or death from any cause, whichever occurs first, as assessed by a central independent review committee (IRC). Participants without documented progression or death will be censored according to the Statistical Analysis Plan.
Duration of Response (DoR) per RANO
Among participants who achieve a complete response or partial response according to RANO criteria, duration of response is measured from the first date on which criteria for complete response or partial response are met until the first date on which recurrent or progressive disease is objectively documented or death occurs, as assessed by a central independent review committee (IRC).
T-cell priming
Rate and magnitude of antigen-specific T-cell responses induced by BreakVax in peripheral blood
Tumor T-cell infiltration
On-treatment tumor biopsy intratumoral and stromal T-cell infiltration
Tumor microenvironment modulation
Change in tumor-associated immune cell populations, including macrophage polarization (e.g., M1/M2 markers), and other immunosuppressive or activation signatures
Click on the lead sponsor to view all of their trials.
BreakBio Corp
Lead sponsor
Miami Cancer Institute
Collaborator
This trial is not recruiting at the moment. You can still explore other options:
