Combination Immunotherapy Treatment for Glioblastoma 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

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 \