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
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
10
An 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
Low-dose subcutaneous ipilimumab at the injection site as a dendritic cell adjuvant to enhance local dendritic cell-mediated T-cell priming
To mitigate PD-1-mediated T-cell exhaustion and sustain effector function
May promote immunogenic cell death, increase antigen release and modulate the tumor microenvironment
Have been associated in preclinical and translational studies with modulation of stromal architecture, vascular normalization, and reduction of tumor-associated immunosuppressive signaling
Miami Herbert Wertheim Cancer Institute
Miami, Florida, United States
Overall Survival (OS)
Time frame: 12 Months
Percentage of patients for whom BreakVax is successfully manufactured
Time frame: up to 24 Months
Adverse events
Time frame: up to 24 Months
T-cell infiltration
Change in tumor-infiltrating T-cells between the pre-treatment biopsy and the on-treatment biopsy
Time frame: From pre-treatment biopsy to on-treatment biopsy (Cycle 2 after imaging)
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).
Time frame: From start of study treatment through disease progression or end of treatment, up to 2 years.
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.
Time frame: From start of study treatment through progression or death, up to 2 years.
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).
Time frame: From first documented CR or PR through progression or death, up to 2 years.
Clinical Benefit Rate (CBR) per RANO
Percentage of participants who achieve complete response (CR), partial response (PR), or stable disease (SD) lasting at least 12 weeks according to RANO criteria, as assessed by a central independent review committee (IRC).
Time frame: From start of study treatment through disease progression or end of treatment, up to 2 years.
Objective Response Rate (ORR) per RANO
Percentage of participants with measurable enhancing disease at baseline who achieve a complete response (CR) or partial response (PR) according to RANO criteria, as assessed by a central independent review committee (IRC).
Time frame: From start of study treatment through disease progression or end of treatment, up to 2 years.
Immune-related Progression-Free Survival (irPFS) per iRANO
Time from the start of study treatment to confirmed disease progression according to iRANO criteria or death from any cause, whichever occurs first. Unconfirmed progression does not constitute a progression event until confirmation according to iRANO criteria.
Time frame: From start of study treatment through confirmed progression or death, up to 2 years.
Incidence of Pseudoprogression per iRANO
Percentage of participants who experience apparent radiographic progression that is subsequently determined not to represent true disease progression according to iRANO criteria.
Time frame: From start of study treatment through disease progression or end of treatment, up to 2 years.
Stable Disease for at Least 12 Weeks per iRANO
Percentage of participants whose best response is stable disease according to iRANO criteria for at least 12 weeks, using the protocol-specified assessment window of 12 weeks ±1 week.
Time frame: From start of study treatment through disease progression or end of treatment, up to 2 years.
Overall Survival (OS)
Time from the start of study treatment to death from any cause.
Time frame: Up to 5 years.
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