Phase I Open-Label Study of P1101 Followed by P1801 in Advanced Solid Tumors

Inclusion criteria

• Willing to provide written informed consent;
• Age ≥18 years;
• Patients with histologically or cytologically confirmed metastatic or locally advanced solid tumors who have progressed despite standard therapy or are intolerant to standard therapy or for whom there is no standard therapy;
• Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 1 at trial entry and an estimated life expectancy of at least 3 months;
• Dose Escalation Phase: Patients with an advanced solid tumor, including, but not limited to RCC and CRC; Dose Expansion Phase: Patients with RCC or CRC;
• Prior chemotherapy or immunotherapy must have been completed at least 4 weeks before screening, and all adverse events have either returned to baseline or stabilized;
• Prior systemic radiation therapy must have been completed at least 4 weeks before screening;
• Normal fundoscopic examination by ophthalmologist at screening; major fundoscopic findings including, but not limited to retinal exudates, hemorrhage, detachment, neovascularization, papilloedema, optic atrophy, microaneurysms and macular changes;
• Patient who has normal laboratory values relevant to thyroid function.

Exclusion criteria

• Concomitant disease or condition that could interfere with the conduct of the study in the opinion of the Investigator;
• Patients requiring chronic treatment with systemic corticosteroids in excess of 10 mg daily of prednisone or equivalent or receiving any systemic immunosuppressive medication will be excluded; while topical, inhaled, nasal and ophthalmic steroids are not prohibited;
• Patients with an active autoimmune disease, a documented history of autoimmune disease or syndrome or asthma that requires systemic steroids or immunosuppressive agents;
• Untreated or symptomatic brain metastasis;
• Subjects with any of the following laboratory test or complications:

• Creatinine > l.5 X Upper Limit of Normal (ULN);
• Absolute neutrophil count (ANC) < 1,500/μL;
• Platelet count < 100,000/μL;
• Hemoglobin < 9 g/dL;
• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 2.5 X ULN (> 5 X ULN if liver metastasis), or total bilirubin > 1.5 X ULN
• international normalized ratio (INR) or activated partial thromboplastin time (aPTT) > 1.5 X ULN;
• uncontrolled diabetes mellitus (HbA1c ≥7.4%);
• Any presence of poorly controlled major psychiatric (including but not limited to those with severe depression, severe bipolar disorder, schizophrenia, suicidal ideation or history of suicidal attempt);
• Any presence of poorly controlled cardiovascular (including but not limited to those with uncontrolled hypertension, New York Heart Association (NYHA) class 2 congestive heart failure, uncontrolled arrhythmia, severe coronary arterial stenosis, unstable angina); or with history of stroke or acute myocardial infarction within 3 years prior to screening;
• Female subjects or the spouse of male subjects, with child-bearing potential who are unwilling or unable to practice any highly effective methods of contraception, defined as vasectomy in men, tubal ligation in women, or use of condoms and spermicides, or birth control pills, or intrauterine devices from 28 days prior to Day 1 until the final follow up visit;
• Patients who are pregnant, who have a possibility of being pregnant or who desire to become pregnant during the study period;
• Lactating women;
• History of hypersensitivity reactions to the active ingredients or any excipient of the study drugs; or history of severe hypersensitivity reactions to other monoclonal antibodies;
• Use investigational drug of other clinical trials within 4 weeks prior to screening;
• History of drug-induced pneumonitis or current pneumonitis;
• Active infection requiring systemic antibiotic therapy;
• Patients with HBV DNA ≧ 2,000, positive HCV RNA, or known human immunodeficiency virus (HIV) infection;
• Patients with Common terminology criteria for adverse events (CTCAE) Grade ≥ 3 cardiac disease or with a history of cardiac arrest;
• Receive any vaccination within 4 weeks prior to screening;
• Use telbivudine within 4 weeks prior to screening or those will use telbivudine after screening;
• Use of prohibited medication or herbal remedies within 4 weeks prior to screening;
• History of CTCAE Grade ≥3 immune-related adverse event (AE) that was considered related to prior immune-modulatory therapy or any immune-related AEs that required immunosuppressive therapy.