AGEN1884, an Anti-CTLA-4 Human Monoclonal Antibody in Participants With Advanced or Refractory Cancer and Who Have Progressed With PD-1/PD-L1 Inhibitor as Their Most Recent Therapy

Inclusion Criteria

• Written informed consent.
• ≥18 years of age.
• Histological or cytological diagnosis of solid cancer or lymphoma that is considered incurable and without therapies with established benefit. Biopsy is not necessary for participants with known prior diagnosis, and clinical or radiographic evidence of recurrence. For Phase 2 only: Participants who experienced documented disease progression during treatment with an approved or investigational PD-1/PD-L1 inhibitor as their most recent therapy (2-6 weeks prior to first dose of study drug). This cohort includes participants with histological diagnoses of hepatocellular carcinoma (HCC) (not including atypical histology such as cholangiocarcinoma mix or fibrolamellar hepatocellular carcinoma) who experienced documented disease progression during treatment with an approved or investigational PD-1/PD-L1 inhibitor as their most recent therapy (2-6 weeks prior to first dose of study drug).
• Eastern Cooperative Oncology Group (ECOG) score of 0 or 1.
• Participants in Phase 2 with HCC should have a Child-Pugh score of A or B7 with no encephalopathy or ascites.
• Life expectancy ≥12 weeks.
• Adequate cardiac function (New York Heart Association [NYHA] class ≤II).
• Adequate organ function, defined as absolute neutrophil count (ANC) ≥1,500×10^6/liter (L), absolute lymphocyte count ≥500/cubic millimeters (mm^3), hemoglobin ≥8.0 grams/deciliter (g/dL), and platelet count ≥100,000×10^6/mm^3 without blood growth factors or without transfusions within 1 week of first dose. For participants in Phase 2 with HCC: Platelet count ≥60×10^6/mm^3 and ANC ≥1,000×10^6/L are acceptable provided that the principal investigator assesses these abnormalities as due to liver disease.
• Adequate liver function, defined as aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5× institutional upper limit of normal (ULN), and bilirubin ≤1.5 milligrams/deciliter (mg/dL) × ULN. For participants in Phase 2 with HCC: AST and ALT ≤5 × ULN, bilirubin ≤2 mg/dL × ULN, and albumin ≥2.8 mg/dL.
• Adequate renal function, defined as estimated creatinine clearance ≥50 milliliters/minute according to Cockcroft-Gault formula, or measured 24-hour creatinine clearance (or local institutional standard method).
• Adequate coagulation defined by international normalized ratio (INR) or prothrombin time (PT) ≤1.5× ULN (unless the participant is receiving anticoagulant therapy); and activated partial thromboplastin time ≤1.5× ULN (unless the participant is receiving anticoagulant therapy). Participants in Phase 2 with HCC can have an INR ≤2.3× ULN. Note: Participants in Phase 2 with HCC and on anticoagulant treatment would have an assigned value of 1 point when scoring PT/INR so the overall Child-Pugh score is not adversely affected.
• Female participants of childbearing potential and fertile male participants must agree to use adequate contraception or abstain from sexual activity from the time of consent through 90 days after the end of study drug. Adequate contraception includes condoms with contraceptive foam; oral, implantable, or injectable contraceptives; contraceptive patch; intrauterine device; diaphragm with spermicidal gel; or a sexual partner who is surgically sterilized or postmenopausal. Note: Abstinence is acceptable if this is the established and preferred contraception for the participant.
• In the expansion phase, all participants must provide a sufficient and adequate formalin-fixed paraffin embedded (FFPE) tumor tissue sample preferably collected after progression on the last therapy and/or collected at screening, if clinically feasible. If a recent biopsy is not available, an archival FFPE sample should be provided from a site not previously irradiated. If no tumor tissue is available, a fresh biopsy will be required if clinically feasible.

Exclusion Criteria

• Other malignancies treated within the last 5 years, except in situ cervix carcinoma or non-melanom