For inclusion in the trial, all of the following inclusion criteria must be fulfilled, as no waivers will be permitted: 1. Provision of signed and dated written informed consent prior to any study specific procedures. Participation in pharmacogenomics (PGx) testing is optional. 2. = 18 years of age. 3. Histologically or cytologically confirmed diagnosis of metastatic or locally advanced solid tumor for which no standard therapy is available or standard therapy has failed. 4. Measurable disease on imaging based on Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1). 5. Life expectancy of = 3 months and Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. 6. Adequate organ and bone marrow reserve function, as indicated by the following laboratory values: 1. Adequate hematological function, defined as absolute neutrophil count (ANC) = 1.5 × 109/L, platelet count = 100 × 109/L, and hemoglobin = 8 g/dL without recent transfusion (defined as a transfusion that has occurred within 2 weeks of the hemoglobin measurement). 2. Adequate liver function, defined as total bilirubin level = 1.5 × institutional upper limit of normal (IULN), aspartate aminotransferase (AST) = 2.5 × IULN, and alanine aminotransferase (ALT) = 2.5 × IULN. 3. Adequate renal function defined as creatinine = 1.5 × IULN OR measured or calculated creatinine clearance = 40 mL/min per institutional standard. Assessment methods should be recorded. 4. Adequate coagulation, defined as international normalized ratio (INR) or prothrombin time = 1.5 × IULN and activated partial thromboplastin time (aPTT) = 1.5 × IULN (unless patient receiving anticoagulant therapy). 7. No history of prior or concomitant malignancy that requires other active treatment. 8. Patients must provide a sufficient and adequate formalin-fixed paraffin embedded (FFPE) tumor tissue sample (fresh biopsy) collected within 28 days before the first dose from a site not previously irradiated, and agree to a mandatory on-treatment biopsy if clinically feasible 9. Female patients of childbearing potential must have a negative serum pregnancy test at screening (within 72 hours of first dose of study medication). Non-childbearing potential is defined as 1 of the following: 1. = 45 years of age and has not had menses for >1 year. 2. Amenorrheic for > 2 years without a hysterectomy and/or oophorectomy and follicle stimulating hormone value in the postmenopausal range upon pretrial (screening) evaluation. 3. Status is post-hysterectomy, -oophorectomy, or -tubal ligation. 10. Female patients of childbearing potential must be willing to use highly effective contraceptive measures starting with the Screening visit through 90 days after last dose of study treatment. Note: Abstinence is acceptable if this is the established and preferred contraception for the patient. 11. Male patients with a female partner(s) of childbearing potential must agree to use highly effective contraceptive measures throughout the trial starting with the Screening visit through 90 days after the last dose of study treatment is received. Males with pregnant partners must agree to use a condom; no additional method of contraception is required for the pregnant partner. Note: Abstinence is acceptable if this is the established and preferred contraception method for the patient

For inclusion in the trial, subject must meet none of the following exclusion criteria, as no waivers will be permitted: 1. Currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigation device within 3 weeks of first dose of current study drug. 2. Received prior systemic cytotoxic chemotherapy, biological therapy, radiotherapy, or major surgery within 3 weeks prior to first dose of study drug. A 1-week washout is permitted for palliative radiation to non-central nervous system (CNS) disease, with Sponsor approval. 3. Patients who have received prior CTLA-4 therapy may be enrolled in selected indications upon agreement with the Sponsor. Note: Selected expansion cohorts may accept prior therapy with anti-CTLA-4 antibody or agent. 4. Persistent toxicity of National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 Grade > 1 severity that is related to prior therapy. Note: Sensory neuropathy or alopecia of Grade = 2 are acceptable. 5. Expected to require any other form of systemic or localized antineoplastic therapy while on trial (including maintenance therapy with another agent, radiation therapy, and/or surgical resection). 6. Known severe (Grade = 3) hypersensitivity reactions to fully human monoclonal antibodies, antibody, or severe reaction to immuno-oncology agents, such as colitis or pneumonitis requiring treatment with steroids; or has a history of interstitial lung disease, any history of anaphylaxis, or uncontrolled asthma. 7. Receiving systemic corticosteroid therapy 1 week prior to the first dose of study drug or receiving any other form of systemic immunosuppressive medication. Note: Corticosteroid use as a premedication for IV contrast allergies/reactions is allowed. Patients who are receiving daily corticosteroid replacement therapy are also an exception to this rule. Daily prednisone at doses of = 7.5 mg or equivalent hydrocortisone dose are examples of permitted replacement therapy. Use of inhaled or topical corticosteroids is permitted. 8. CNS tumor, metastasis(es), and/or carcinomatous meningitis identified either on the baseline brain imaging obtained during the screening period or identified prior to consent. Note: Patients with history of brain metastases that have been treated may participate provided they show evidence of stable supra-tentorial lesions at screening (defined as 2 brain images, both of which are obtained after treatment to the brain metastases and obtained = 4 weeks apart). In C-800-01 Agenus, Inc. Protocol Amendment 4 22 July 2020 Confidential Page 15 of 124 addition, any neurologic symptoms that developed either as a result of the brain metastases or their treatment must have returned to baseline or resolved. Any steroids administered as part of this therapy must be completed =3 days prior to first dose of trial medication. 9. Active or history of autoimmune disease that requires systemic treatment within 2 years of the start of study drug (i.e., with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs). Note: Patients with autoimmune conditions requiring hormone replacement therapy or topical treatments are eligible. 10. Has had an allogeneic tissue/solid organ transplant, except for corneal transplants. 11. Active infection requiring treatment. 12. Known history of human immunodeficiency virus (HIV) type 1 or 2 antibodies. 13. Known active infection with hepatitis B and/or hepatitis C virus. 14. Clinically significant (i.e., active) cardiovascular disease: cerebral vascular accident/stroke or myocardial infarction within 6 months of enrollment, unstable angina, congestive heart failure (New York Heart Association class = II), or serious uncontrolled cardiac arrhythmia requiring medication. 15. History or current evidence of any condition, therapy, any active infections, or laboratory abnormality that might confound the results of the trial, interfere with the patient's participation for the full duration of the trial, or is not in the best interest of the patient to participate, in the opinion of the treating Investigator. 16. Known psychiatric or substance abuse disorder that would interfere with cooperation with the requirements of the trial. 17. Legally incapacitated or has limited legal capacity. 18. Pregnant or breastfeeding.