A Clinical Trial to Evaluate the Safety, Tolerability and Clinical Efficacy of M3T01 Monotherapy and in Combination With Pembrolizumab and Other Systemic Therapies

Inclusion Criteria: 1. Age ≥ 18 years. 2. Life expectancy ≥ 12 weeks. 3. Provision of written informed consent (see Section 16.1 and Appendix 18.5.5) for participation in the clinical trial. 4. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0-1 for subjects with solid tumors other than glioblastoma. 5. Karnofsky Performance Status of ≥ 70% for subjects with glioblastoma. 6. Tumor tissue from a surgical or core needle biopsy must be provided to the sponsor (fine needle aspirate or cytology specimens are not acceptable). Archival formalin fixed paraffin embedded (FFPE) tissue is acceptable. If archival tumor tissue is not available, a fresh tumor biopsy must be performed. 7. Subjects must have a tumor accessible for biopsy while on treatment. If the subject does not have a tumor that is safely accessible for biopsy, the subject may still participate in the clinical trial following authorization from the sponsor. NOTE: Subjects with glioblastoma are not required to have tumor accessible for biopsy and will not undergo a protocol specified biopsy on study. 8. Eligible tumor types in Part 1 Dose Escalation will include subjects with histologically or cytologically confirmed metastatic or unresectable solid tumors who have developed disease progression following standard systemic therapy in the unresectable or metastatic setting. Subjects with cancers that harbor a molecularly defined oncogenic target for which an FDA approved therapy is available (including but not limited to EGFR, ROS1, ALK, BRAF, RET, NTRK, KRAS G12C, etc.) should have received this therapy. 9. Measurable disease * Subjects with solid tumors other than glioblastoma must have measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. * Subjects with glioblastoma: Part 1: must have measurable disease per Response Assessment in Neuro-Oncology (RANO 2.0); Part 2: measurable disease at baseline is not required as these subjects will have undergone maximal safe resection prior to enrollment. 10. Adequate organ function as defined by the following: * Absolute neutrophil count (ANC) ≥ 1.2 x 109/L. * Hemoglobin ≥ 9.0 g/dL (without a blood transfusion 2 weeks prior to the hemoglobin measurement). * Platelet count ≥ 100 x 109/L (without a platelet transfusion 2 weeks prior to the platelet measurement). * Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 x ULN. * Total bilirubin ≤ 1.5 x ULN (or ≤ 3 x ULN for subjects with Gilbert's syndrome). * International normalized ratio (INR) ≤ 1.5 x ULN and activated partial thromboplastin time (aPTT) ≤ 1.5 x ULN (unless the subject is being treated with anticoagulant medication). * Serum albumin ≥ 2.8 g/dL. * Creatinine clearance (measured or calculated) ≥ 30 mL/min. 11. Female subjects of reproductive potential who are sexually active with a male partner must: * Have a negative serum beta-human chorionic gonadotropin (β-HCG) test within 3 days of cycle 1 day 1. * Agree to use highly effective contraceptive measures (as defined in protocol) from the time of enrollment through 3 months after the last dose of study drug in the clinical trial. * Female subjects are considered to be of non-reproductive potential if they: have been amenorrheic for greater than 1 year or have undergone surgical sterilization through tubal ligation, oophorectomy or hysterectomy. 12. Male subjects with a female partner of reproductive potential must agree to use highly effective contraception (as defined in protocol) from the time of enrollment through 3 months after the last dose of study drug administration. 13. Subjects must agree to not donate sperm or eggs (ova, oocytes) for the purpose of reproduction from the time of enrollment through 3 months after the last dose of study drug administration. 14. Toxicities from prior anti-cancer therapy must have resolved to grade ≤ 1. * Exceptions include vitiligo, endocrinopathies managed with hormone replacement therapy, alopecia, and grade 2 neuropathy or hearing loss. Exclusion Criteria: 1. Treatment with anticancer therapy within 14 days or 5 half-lives (whichever is shorter) of cycle 1 day 1. Palliative radiation therapy to a non-CNS metastasis is permitted if completed at least 14 days prior to cycle 1 day 1. 2. History of other active malignancy that required treatment within 2 years of enrollment. Exceptions include the following: * Early-stage/localized tumors that have received definitive/curative treatment and have low risk of recurrence (including but not limited to cutaneous squamous cell or basal cell carcinoma, in situ cervical or bladder cancer, and early-stage prostate cancer). * Early-stage prostate cancer in which observation without treatment is recommended. 3. Clinically significant cardiovascular conditions as defined by the following: * New York Heart Association (NYHA) congestive heart failure class ≥ II. * Left ventricular ejection fraction ≤ 50%. * Clinically significant cardiac arrhythmia requiring treatment within 3 months of enrollment. Subjects with cardiac arrhythmias on stable management for over 3 months prior to enrollment are permitted. * Prolonged QTcF interval \> 480 ms. * Myocardial infarction, stroke, or pulmonary embolism within 3 months of enrollment. 4. CNS metastases or leptomeningeal carcinomatosis (applicable to subjects with solid tumors other than glioblastoma). Subjects with brain metastases are eligible for participation if one of the following criteria are met: * CNS metastases have been treated with surgical resection or radiation therapy and have remained stable for at least 4 weeks (repeat imaging required at least 4 weeks following resection or last radiation therapy) prior to cycle 1 day 1. * The subject is neurologically asymptomatic and there are ≤ 4 CNS metastases no larger than 1 cm. 5. Treatment with immunosuppressive medications. \- Treatment with corticosteroids greater than the equivalent of prednisone 10 mg/day within 2 weeks of cycle 1 day 1 is exclusionary. Exceptions include: Premedication with corticosteroids for iodine contrasted CT scans; Chronic use of ≤ 10 mg/day of prednisone (or equivalent). Topical, inhaled, and intra-articular corticosteroid use is allowed; Subjects with glioblastoma are permitted to be on ≤ 3 mg/day dexamethasone (or equivalent). 6. History of severe pulmonary disease defined as either of the following: * History of interstitial lung disease, non-infectious pneumonitis (including immune checkpoint inhibitor induced pneumonitis), or pulmonary fibrosis. * Currently dependent on supplemental oxygen. 7. History of allogeneic stem cell or solid organ transplantation. 8. History of autoimmune disease that required systemic immunosuppressive therapy within 2 years of enrollment. Subjects with autoimmune diseases managed with hormone replacement or topical therapies are eligible. 9. History of an immune-mediated adverse event from treatment with an immune checkpoint inhibitor that resulted in treatment discontinuation. \- Subjects who discontinued treatment with ipilimumab due to toxicity and subsequently tolerated treatment with an anti-PD-(L)1 inhibitor without treatment-limiting toxicity are eligible. 10. History of severe hypersensitivity reaction (≥ grade 3) to infusion of a therapeutic monoclonal antibody. 11. Any major surgery within 4 weeks of receiving the first dose of the investigational treatment. 12. Women who are pregnant or breast feeding. 13. Subjects with active (acute or chronic) bacterial, viral, or fungal infection at the time of enrollment are ineligible with the following exceptions: * Subjects with human immunodeficiency virus (HIV) are eligible for participation if the following criteria are met: CD4+ T cell count ≥350 cells/µL, No history of AIDS-defining opportunistic infections within 12 months of enrollment, Subjects must be on antiretroviral therapy for at least 4 weeks and have an HIV viral load less than 400 copies/mL prior to enrollment. * Subjects with chronic hepatitis B (HBV) who are on suppressive antiviral therapy prior to enrollment are eligible. Subjects with chronic HBV who are not eligible for treatment with suppressive antiviral therapy are ineligible. * Subjects with a history of hepatitis C (HCV) infection who have completed curative antiviral treatment and have an HCV viral load below the limit of quantification are eligible. 14. Ongoing drug or alcohol abuse at the time of enrollment. 15. Any medical or psychiatric illness or social circumstance that could jeopardize compliance with the protocol directed treatment and safety assessments. Additional Exclusion Criteria Specific for the Part 2A - Newly Diagnosed MGMT Unmethylated Glioblastoma Cohort: 1. Subjects with recurrent or secondary GBM. 2. Subjects who underwent biopsy only without maximal safe resection. 3. Subjects with a contraindication to MRI scans. 4. Subjects with IDH-1 or IDH-2 mutations or H3 K27M diffuse midline glioma. 5. Subjects with unresolved CNS hemorrhage, leptomeningeal or spinal metastases or ventricular invasion. 6. Subjects treated with a carmustine wafer implant. 7. Subjects treated with Tumor Treating Fields (TTF).