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

Phase 1/2 Trial of a Combination Immunotherapy Treatment for Solid Tumors Including BreakVax ImmunoTreatment (Designed and Manufactured Per Patient), Chemotherapy and Anti PD-1 Therapy

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 Overview

• Status: Not yet recruiting
• Conditions: Glioblastoma (GBM)
• Intervention / Treatment: Drug: BreakVax; Drug: Ipilimumab 2.5 mg; Drug: Pembrolizumab; Drug: Temozolomide (TMZ); Drug: Losartan and aspirin

• Study Type: Interventional
• Enrollment (Estimated): 10
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Miami, Florida, United States, 33176
      • Miami Herbert Wertheim Cancer Institute
      • Principal Investigator: Manmeet Ahluwalia, MD, MBA, FASCO

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age ≥ 18 years and < 72
2. 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.
3. KPS of 80 or greater on day of first dose

4. 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
   • Pulse oximetry ≥ 92% on room air.
5. Provision of consent for on-treatment biopsy (compulsory) and post-treatment biopsy (optional).
6. Both male and female patients enrolled in this trial must agree to use effective contraception during the course of the trial and for at least 3 months after discontinuing study treatment. Patients and/or partners who are surgically sterile or postmenopausal are exempt from this requirement.
7. Negative pregnancy test ≤ 7 days prior to day one of cycle 1, for women of childbearing potential only.
8. Life expectancy > 6 months.
9. Willing and able to provide informed consent

Exclusion Criteria:

1. Prior exposure to anti PD- 1/PD-L1 agents.
2. Prior exposure to immunosuppressive therapy within the last 12 months prior to enrollment.
3. 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.
4. Patients with deficient mismatch repair (dMMR) or microsatellite instability (MSI-H) phenotype
5. 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.
6. 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.
7. Patients not recovered adequately from the toxicity and/or complications from any major surgery prior to starting study treatment.
8. Known or suspected hypersensitivity to any of the study drugs.
9. Received an investigational agent within 28 days prior to the first dose of study drug.
10. 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.
11. LVEF <50%.
12. Active interstitial lung disease (ILD)/pneumonitis or a history of ILD/pneumonitis requiring treatment with systemic steroids.
13. 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.
14. 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.
15. 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.
16. Receiving coumarin-derived anticoagulants.
17. Unable or unwilling to withhold or discontinue any prohibited or restricted medications/procedures for the specified windows during the study.
18. Inability or refusal to comply with the protocol or with the clinical trial procedures.
19. If female, pregnant or breastfeeding. All female patients with reproductive potential must have a negative pregnancy test prior to starting treatment.
20. Chronic intake of drugs that lead to known interference with metabolism through strong Cytochrome P450 3A4 (CYP3A4) interaction: e.g. Rifampicin, Rifabutin, Clarithromycin, Telithromycin, Ketoconazole, Itraconazole, Fluconazole, Hypericum perforatum (St. John's Wort /Johanniskraut) or any strong CYP3A4 inducing or inhibiting drug (Note: participants in this study should avoid consuming grapefruit or grapefruit-containing products during the duration of the study, including the screening phase, treatment period, and follow-up period).
21. Uncontrolled hypertension defined as persistent systolic blood pressure ≥ 150 mmHg or diastolic blood pressure ≥ 100 mmHg despite current therapy.
22. Arterial thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks) within 6 months before the start of study medication. Active pulmonary emboli or deep vein thrombosis that are significant or not adequately controlled on anticoagulation regimen
23. Any hemorrhage or bleeding event ≥ National Cancer Institute - Common terminology criteria for adverse events (NCI-CTCAE) Grade 3 within 28 days prior to the start of study medication
24. History of other invasive cancer within 2 years prior to enrollment, except for treated non-melanoma skin cancer
25. Known DNA Polymerase Epsilon (POLE) mutations

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: BreakVax Arm; 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; 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; Drug: Ipilimumab 2.5 mg; Low-dose subcutaneous ipilimumab at the injection site as a dendritic cell adjuvant to enhance local dendritic cell-mediated T-cell priming; Drug: Pembrolizumab; To mitigate PD-1-mediated T-cell exhaustion and sustain effector function; Drug: Temozolomide (TMZ); May promote immunogenic cell death, increase antigen release and modulate the tumor microenvironment; Drug: Losartan and aspirin; Have been associated in preclinical and translational studies with modulation of stromal architecture, vascular normalization, and reduction of tumor-associated immunosuppressive signaling

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
T-cell infiltration	Change in tumor-infiltrating T-cells between the pre-treatment biopsy and the on-treatment biopsy	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).	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.	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).	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).	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).	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.	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.	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.	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.	Up to 5 years.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
T-cell priming	Rate and magnitude of antigen-specific T-cell responses induced by BreakVax in peripheral blood	24 Months
Tumor T-cell infiltration	On-treatment tumor biopsy intratumoral and stromal T-cell infiltration	24 Months
Tumor microenvironment modulation	Change in tumor-associated immune cell populations, including macrophage polarization (e.g., M1/M2 markers), and other immunosuppressive or activation signatures	24 Months

Collaborators and Investigators

• Sponsor: BreakBio Corp
• Collaborators: Miami Cancer Institute

Study record dates

Study Major Dates

• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): September 1, 2030
• Study Completion (Estimated): September 1, 2030

Study Registration Dates

• First Submitted: August 7, 2026
• First Submitted That Met QC Criteria: August 11, 2026
• First Posted (Actual): August 13, 2026

Study Record Updates

• Last Update Posted (Actual): August 19, 2026
• Last Update Submitted That Met QC Criteria: August 18, 2026
• Last Verified: August 1, 2026

More Information

Terms related to this study

• Keywords: GBM; Glioblastoma
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioblastoma; Amino Acids, Peptides, and Proteins; Proteins; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Azoles; Hydrocarbons; Hydrocarbons, Cyclic; Hydrocarbons, Aromatic; Dacarbazine; Triazenes; Imidazoles; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Phenols; Benzene Derivatives; Salicylates; Hydroxybenzoates; Tetrazoles; Biphenyl Compounds; Temozolomide; Ipilimumab; Aspirin; Losartan; pembrolizumab
• Other Study ID Numbers: BreakBio-3 Substudy B

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No