Combination Immunotherapy Treatment for Glioblastoma Including BreakVax ImmunoTreatment (Designed and Manufactured Per Patient), Chemotherapy and Anti PD-1 Therapy

NCT07762716 | Not Yet Recruiting Phase 1 FDA Drug

• 1 other identifier: BreakBio-3 Substudy B
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

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. 1.Low-dose subcutaneous ipilimumab at the injection site as a dendritic cell adjuvant to enhance local dendritic cell-mediated T-cell priming;
2. 2.Pembrolizumab to mitigate PD-1-mediated T-cell exhaustion and sustain effector function;
3. 3.Standard-of-care chemotherapy, which may promote immunogenic cell death, increase antigen release and modulate the tumor microenvironment; and
4. 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.

Conditions

Glioblastoma (GBM)

Keywords

Glioblastoma; GBM

Outcome Measures

Primary Outcomes (3)

• Overall Survival (OS)

  12 Months

• Percentage of patients for whom BreakVax is successfully manufactured

  up to 24 Months

• Adverse events

  up to 24 Months

Secondary Outcomes (10)

• T-cell infiltration

  From pre-treatment biopsy to on-treatment biopsy (Cycle 2 after imaging)

• Immune-related Objective Response Rate (irORR) per iRANO

  From start of study treatment through disease progression or end of treatment, up to 2 years.

• Progression-Free Survival (PFS) per RANO

  From start of study treatment through progression or death, up to 2 years.

• Duration of Response (DoR) per RANO

  From first documented CR or PR through progression or death, up to 2 years.

• Clinical Benefit Rate (CBR) per RANO

  From start of study treatment through disease progression or end of treatment, up to 2 years.

Other Outcomes (3)

• T-cell priming

  24 Months

• Tumor T-cell infiltration

  24 Months

• Tumor microenvironment modulation

  24 Months

Study Arms (1)

BreakVax Arm

EXPERIMENTAL

A cycle for this study is defined as 28 days. BreakVax along with adjuvants and low-dose subcutaneous ipilimumab (as an adjuvant) will be administered on Day 1 and D15 of Cycle 1, and will then be administered on D1 of every cycle thereafter until disease progression per RANO criteria. In addition to BreakVax, patients in the BreakVax Arm will receive losartan daily and temozolomide - without steroid pre-medications (see disallowed concomitant treatment below). Patients will receive aspirin QD except the day BreakVax is administered and the 2 following days in cycles in which the patient is receiving BreakVax. Patients will begin pembrolizumab on Day 21 of Cycle 2 and it will then be administered every 6 weeks thereafter

Drug: BreakVax; Drug: Ipilimumab 2.5 mg; Drug: Pembrolizumab; Drug: Temozolomide (TMZ); Drug: Losartan and aspirin

Interventions

BreakVax DRUG

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

BreakVax Arm

Ipilimumab 2.5 mg DRUG

Low-dose subcutaneous ipilimumab at the injection site as a dendritic cell adjuvant to enhance local dendritic cell-mediated T-cell priming

BreakVax Arm

Pembrolizumab DRUG

To mitigate PD-1-mediated T-cell exhaustion and sustain effector function

BreakVax Arm

Temozolomide (TMZ) DRUG

May promote immunogenic cell death, increase antigen release and modulate the tumor microenvironment

BreakVax Arm

Losartan and aspirin DRUG

Have been associated in preclinical and translational studies with modulation of stromal architecture, vascular normalization, and reduction of tumor-associated immunosuppressive signaling

BreakVax Arm

Eligibility Criteria

• Age: 18 Years - 72 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• Patient has adequate organ function on day one of the trial as defined by:
• Neutrophil to Lymphocyte Ratio (NLR)1 at a healthy adult's normal level: ≤ 3.5
• Absolute Neutrophil Count (ANC) at the normal level: ≤ 7,000/mm3
• Absolute Lymphocyte Count in normal level: ≥ 1,000/mm3
• Monocytes at normal level: \< 700/mm3
• Platelet count: ≥ 100 x 109/L (without transfusion support in the last two weeks)
• Hemoglobin: \> 10.0 g/dL (without transfusion support in the last two weeks)
• AST and ALT: ≤ 3 X institutional upper limit of normal (ULN) in the absence of liver mets; AST and/or ALT may be ≤ 5 x ULN in the setting of liver metastases
• Total Bilirubin at the normal level: ≤ 1.2mg/dL
• Serum creatinine: ≤ 1.5 x institution's ULN
• Albumin at the normal level: ≥ 3.4 g/dL
• Serum Magnesium at normal level: ≥ 1.7 mg/dL

You may not qualify if:

• 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
• Any liver metastasis greater than 2 cm or greater than 5 liver metastases. Patients who have liver metastasis removed by surgery, and therefore meet this criterion at first dose, may enroll.
• Patients not recovered from all clinically significant toxic effects of previous therapies to ≤Grade 1 or baseline with the exception of peripheral neuropathy and alopecia.
• Patients not recovered adequately from the toxicity and/or complications from any major surgery prior to starting study treatment.
• Known or suspected hypersensitivity to any of the study drugs.
• Received an investigational agent within 28 days prior to the first dose of study drug.
• History of myocarditis or congestive heart failure (as defined by New York Heart Association Functional Classification III or IV), as well as unstable angina, serious uncontrolled cardiac arrhythmia, uncontrolled infection, or myocardial infarction within the past 6 months. Note: Prior to trial entry, any ECG abnormality at screening must be documented by the investigator as not medically relevant.
• LVEF \<50%.
• Active interstitial lung disease (ILD)/pneumonitis or a history of ILD/pneumonitis requiring treatment with systemic steroids.
• Known history of Hepatitis B (defined as Hepatitis B surface antigen \[HBsAg\] reactive) or known active Hepatitis C virus (defined as HCV RNA \[qualitative\] is detected) infection. Note: no testing for Hepatitis B and Hepatitis C is required unless mandated by local health authority. Individuals who are hepatitis C antibody positive may be enrolled if negative viral load confirmed.
• History of autoimmune disease including inflammatory bowel disease (including ulcerative colitis and Crohn's Disease), rheumatoid arthritis, systemic progressive sclerosis (scleroderma), systemic lupus erythematosus, autoimmune vasculitis (e.g. Wegener's granulomatosis); central nervous system or motor neuropathy considered of autoimmune origin (e.g. Guillain-Barré syndrome, myasthenia gravis, multiple sclerosis). Individuals with vitiligo, Sjogren's Syndrome, interstitial cystitis, Graves' or Hashimoto's Disease, celiac disease, DM1, hypothyroidism stable on hormone replacement, or any autoimmune disease without symptoms and not requiring active therapy for at least 2 years will be allowed with Study Medical Monitor's approval.
• A serious local infection (e.g. cellulitis, abscess) or systemic infection (e.g. pneumonia, septicemia) which requires systemic antibiotic treatment within 4 weeks prior to the first dose of study medication.

Sponsors & Collaborators

• BreakBio Corp: lead
• Miami Cancer Institute: collaborator

Study Sites (1)

Miami Herbert Wertheim Cancer Institute

Miami, Florida, 33176, United States

Location

MeSH Terms

Conditions

Glioblastoma

Interventions

Ipilimumab; pembrolizumab; Temozolomide; Losartan; Aspirin

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Biphenyl Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Tetrazoles; Salicylates; Hydroxybenzoates; Phenols

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 7, 2026
• First Posted: August 13, 2026
• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): September 1, 2030
• Study Completion (Estimated): September 1, 2030
• Last Updated: August 13, 2026

Record last verified: 2026-08

Locations

US (1)