Imaging Perfusion Restrictions From Extracellular Solid Stress - An Open-label Losartan Study

Inclusion Criteria:

1. A histologically confirmed intracranial glioblastoma, WHO grade 4 (Study A), or a minimum of one radiographically confirmed metastasis to the brain from a primary non-small-cell lung cancer (Study B)
2. Ability to undergo an MRI exam, including administration of a standard clinical dose of an MRI-specific contrast agent of gadolinium or similar
3. Measurable intracranial disease (Study A - recurrent glioblastoma, and Study B only), defined as at least one lesion that can be accurately measured in at least one dimension as ≥10 mm with MRI
4. Age ≥18 years
5. Eligible for administration of the active substance (losartan) in concordance with study protocol, the criteria of the product label (Cozaar) and deemed fit for trial by the treating physician.
6. An ECOG performance status of ≤2 or equivalent KPS of ≥60%
7. Life expectancy from start of treatment of more than 3 months
8. Previous history of neurosurgical procedure (Study A - only) or stereotactic radiosurgery and immunotherapy (Study B) at time of study inclusion
9. Scheduled for chemotherapy and/or radiotherapy and/or stereotactic radiosurgery (Study A - recurrent glioblastoma), neurosurgery, radiotherapy and chemotherapy (Study A - newly diagnosed glioblastoma), immunotherapy and/or chemotherapy (Study B)
10. Pre-study documentation on O6-methylguanin-DNA-methyltransferase (MGMT) promoter methylation status and on the isocitrate dehydrogenase (IDH) gene mutation status of their disease (study A only)
11. Organ functions of sufficient quality and robustness to undergo study treatment as determined by the study principal investigator (PI) or designee
12. Female patients of childbearing potential (postmenarcheal, not postmenopausal (\>12 continuous months of amenorrhea with no identified cause other than menopause), and no surgical sterilization) should use highly effective contraception and take active measures to avoid pregnancy while undergoing IMP treatment and for at least 14 days after the last dose. Birth control methods considered to be highly effective include combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal or transdermal), progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable or implantable), intrauterine device, intrauterine hormone-releasing system, bilateral tubal occlusion, vasectomized partner, sexual abstinence when it is the preferred and usual lifestyle of the subject.
13. Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

1. Hypersensitivity to the active substance (losartan) or to any of the excipients
2. Patients on antihypertensive agents that cannot be substituted with losartan.
3. Patients on medication that may induce hypotension and/or increase potassium levels and/or cause metabolism-related pharmacokinetic drug-drug interactions with losartan. If medication with such effects can safely be discontinued or replaced, the patient can be included in the study after a washout period before baseline.
4. Patients with hepatic or renal impairment of any reason
5. Patients with symptomatic hypotension of any reason
6. Patients with primary hyperaldosteronism
7. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucosegalactose malabsorption should not take this medicine
8. Inadequate recovery from toxicity and/or complications of previous therapy as determined by the treating physician
9. Patients with evidence of recurrence inside the radiotherapy target volume less than 3 months since last radiotherapy fraction (Study A - recurrent glioblastoma only)
10. For Study B subjects only. A diagnosis of immunodeficiency or hypersensitivity to the PD-1 inhibitors or any of its excipients
11. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, coronary heart disease and cerebrovascular disease, unstable angina pectoris, cardiac arrhythmia, angioedema, intravascular volume depletion, or psychiatric illness/social situations that would limit compliance with study requirements as determined by treating the physician
12. Patients suffering from aortic or mitral stenosis, or obstructive hypertrophic cardiomyopathy
13. Patient with known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study as determined by the treating physician
14. Pregnant or breastfeeding patient
15. Known additional active non-study related malignancy
16. Applies to Study B patients qualifying for immunotherapy only: Active autoimmune disease that has required systemic treatment in the last 2 years (including use of non-study related disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is allowed
17. Known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies)
18. Unable to undergo brain MRI according to study protocol
19. For Study B subjects only: No previous history of immunotherapy at time of study inclusion.