Phase 1 Study of CI-8993 Anti-VISTA Antibody in Patients With Advanced Solid Tumor Malignancies

The plan is to enroll approximately 50 patients with metastatic or unresectable solid tumor malignancy (non-lymphoma) that is considered relapsed and/or refractory to prior therapy into specific dose cohorts to determine the maximum tolerated dose (MTD) of full doses of CI-8993, based on the occurrence of dose limiting toxicities (DLTs) 28 days from the first full dose. Administration is every 2 weeks. To assure patient safety, each patient will receive an initial low dose of CI-8993 (step-dose) one week prior to their first full dose.

A Safety Review Committee (SRC) will review all safety data and make cohort escalation/de-escalation decisions.

Inclusion criteria

• Patient must be ≥18 years of age
• Patients must have the following disease related criteria:

• any type of solid tumor malignancy (non-lymphoma) that is metastatic or unresectable and considered relapsed and/or refractory to prior therapy
• must have evaluable disease.
• Archival formalin-fixed, paraffin-embedded (FFPE) tumor tissue
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Adequate organ and bone marrow function, in the absence of growth factors.
• Fertility criteria:

• Women of childbearing potential (WOCBP) and fertile males with WOCBP partners must use highly effective contraception
• Women must agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction
• Men must agree not to donate sperm
• A man who is sexually active with a woman of childbearing potential and has not had a vasectomy must agree to use a highly effective method of birth control.
• Patient must be willing and able to adhere to the prohibitions and restrictions specified in the protocol. Due to the possibility of neurologic events, patient must agree to refrain from engaging in hazardous occupations or activities such as operating heavy or dangerous machinery during the first cycle of treatment.
• Each patient must sign an informed consent form (ICF) indicating that he or she understands the purpose and procedures required for the study and is willing to participate in the study.

Exclusion criteria

• Patient has any of the following medical situations:

• Uncontrolled intercurrent illness including, but not limited to: poorly controlled hypertension; poorly controlled diabetes; ongoing active infection requiring antibiotics or acute infectious illness (including suspected viral infection); symptomatic congestive heart failure; unstable angina pectoris; cardiac arrhythmia considered to increase risk for the patient by the Investigator; psychiatric illness that would limit compliance with study requirement
• Medical illness requiring systemic glucocorticoid use > 10mg/day prednisone equivalent.
• Patients with any CNS disorder, such as CNS malignancy/metastasis, stroke, transient ischemic attack, or seizure disorder
• Personal or familial history of hemophagocytic lymphohistiocytosis or macrophage activation syndrome
• An autoimmune disease with a history of flares requiring immunosuppressant medications within the past 6 months
• Prior allogeneic organ or bone marrow transplant (BMT).
• Social situation that would limit compliance with study requirements
• Major surgery (eg, requiring general anesthesia) within 4 weeks before the planned first dose of study drug, or not fully recovered from prior surgery, or has surgery planned during the time the patient is expected to participate in the study or within 4 weeks after the last dose of study drug.
• History of positive testing for hepatitis B surface antigen (HBsAg) or hepatitis C antibody (anti-hepatitis C virus) or other clinically active liver disease, or positive testing at screening for HBsAg or anti- hepatitis C virus.
• History of human immunodeficiency virus (HIV) antibody positive
• Patient has had prior therapy meeting the following:

• Anticancer immunotherapy within 3 weeks prior to the first dose of CI-8993
• Prior T Cell Receptor-modified or chimeric antigen receptor T cell (CART) therapy
• Other anticancer therapy, including chemotherapy, targeted therapy, or treatment with an investigational anticancer agent within 2 weeks prior to the first dose of CI-8993
• Radiotherapy (excluding limited palliative radiation) within 2 weeks of start of CI-8993
• Unresolved toxicities from previous anticancer therapies above Grade 1.
• Immune-related AE with prior immunotherapy that was Grade 3 or higher.
• Patient has known allergies, hypersensitivity, or intolerance to components of CI 8993
• Patient receiving therapeutic anticoagulants
• Fertility exclusions:

• Patient is pregnant, breastfeeding, or planning to become pregnant while enrolled in this study or within 3 months after the last dose of study drug; WOCBP must have a negative pregnancy status confirmed by serum pregnancy test at screening and within 72 hours of first dose of study drug.
• Patient is a man who plans to father a child while enrolled in this study or within 3 months after the last dose of study drug.
• Vaccinated with a live vaccine within 28 days (with the exception of the annual inactivated influenza vaccine) prior to the first dose of study drug