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

Exclusion Criteria

• •1. Other malignancies treated within the last 5 years, except in situ cervix carcinoma or non-melanoma skin cancer.
• •2. Other form(s) of antineoplastic therapy anticipated during the period of the study.
• •3. Previous severe hypersensitivity reaction to another fully human monoclonal antibody or severe reaction to immuno-oncology agents, such as colitis or pneumonitis requiring treatment with steroids.
• •4. History of interstitial lung disease.
• •5. Primary or secondary immunodeficiency, including immunosuppressive disease, autoimmune disease (including autoimmune endocrinopathies), or usage of immunosuppressive medications.
• •Note: Participants with diabetes type 1, vitiligo, psoriasis, hypo-, or hyperthyroid disease not requiring immunosuppressive treatment are eligible. Participants with Type 2 diabetes mellitus are allowed.
• •6. Participants with a known history of human immunodeficiency virus 1 and 2, human T lymphotropic virus 1.
• •Participants in Phase 2 with HCC: Participants with active hepatitis B infection who are receiving effective antiviral therapy are permitted. Participants with active hepatitis C infection are allowed (antiviral therapy not required).
• •7. Administration of anticancer medications or investigational drugs within the following intervals before the first administration of study drug: a. ≤14 days for chemotherapy, targeted small molecule therapy, or radiation therapy. Participants must also not have had radiation pneumonitis as a result of treatment and cannot participate in the study if they are on chronic corticosteroids for radiation pneumonitis. A 1-week washout is permitted for palliative radiation to non-central nervous system (CNS) disease, with medical monitor approval.
• •Note: Bisphosphonates and denosumab are permitted medications. b. ≤14 days for prior immunotherapy. Participants in the dose escalation cohorts are excluded if they have received prior checkpoint inhibitors, costimulatory agonists, or immune modulating therapy except as described below. Once a dose level is determined to be safe by the safety review committee, participants will be allowed to enroll in dose-level expansion cohorts if they have received other non-CTLA-4 targeting immunotherapies.
• •c. Participants enrolling in Phase 2 must have cancer that has progressed after prior 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). The minimum requirement of 2 weeks (14 days) from prior anti-PD-1/PD-L1 therapy is to allow resolution of any lower-grade (≤2) adverse events observed with the therapy. If the investigator feels the participant has tolerated prior anti-PD-1/PD-L1 therapy well, then treatment with study agent may begin sooner.
• •d. ≤7 days for prior corticosteroid treatment, with the following exceptions:
• •* Use of an inhaled or topical corticosteroid is permitted.
• •* Corticosteroid premedication for radiographic imaging for dye allergies is permitted.
• •* Use of physiologic corticosteroid replacement therapy may be approved after consultation with the medical monitor. e. ≤21 days for prior monoclonal antibody used for anticancer therapy, with the exception of denosumab. This does not apply to participants being enrolled in Phase 2, who have received a PD-1/PD-L1 inhibitor as their most recent therapy (2-6 weeks prior to first dose of study drug; see above).
• •f. ≤7 days for immunosuppressive-based treatment for any reason, with the exceptions noted above for prior corticosteroid treatment (exclusion criterion d).
• •g. ≤21 days or 5 half-lives before first dose of study treatment for all other investigational study drugs or devices. For investigational agents with long half- lives (for example, \>5 days), enrollment before the fifth half-life requires medical monitor approval.
• •h. For participants in Phase 2 with HCC \<6 weeks for prior locoregional therapy to the liver, for example, transcatheter chemoembolization, radiation, surgery, or radioembolization.
• •8. Has not recovered to grade ≤1 from toxic effects of prior therapy and/or complications from prior surgical intervention before starting therapy.
• •Note: Participants with grade ≤2 neuropathy and alopecia are an exception and may enroll.
• •9. Uncontrolled infection or other serious medical illnesses.
• •10. History or presence of an abnormal electrocardiogram that, in the investigator's opinion, is clinically meaningful.
• •11. Any medical conditions that, in the opinion of the investigator, would preclude use of AGEN1884, including AGEN1884 hypersensitivity.
• •12. Women who are pregnant or breastfeeding.
• •13. Concurrent participation in other investigational drug trials.
• •14. Has a 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: Participants with history of brain metastases that have been treated may participate provided they show evidence of stable supra-tentorial lesions are obtained after treatment to the brain metastases. These imaging scans should both be obtained ≥4 weeks apart). In addition, any neurologic symptoms that developed either as a result of the brain metastases or their treatment must have returned to baseline or resolved. For individuals who received steroids as part of brain metastases treatment, steroids must be discontinued ≥7 days prior to first dose of study drug.
• •15. For participants in Phase 2 with HCC, the following exclusions also apply:
• •1. Recent encephalopathy episodes in the last 6 months.
• •2. Recent (within the last 6 months) gastro-esophageal varices bleeding.
• •3. Participant whose tumors have cardiac involvement, as determined by imaging.