Safety, Pharmacokinetics and Efficacy of CT-707, Toripalimab and Gemcitabine in Advanced Pancreatic Cancer

Exclusion Criteria

• •1. Patients who have received chemotherapy, biotherapy, endocrine therapy, immunotherapy and other anti-tumor therapy within 4 weeks prior to the first use of the study drug.
• •2. Patients who have received clinical investigational drug or treatment within 4 weeks prior to the first use of the study drug.
• •3. Patients who have received major surgery within 4 weeks or had minor surgery within 2 weeks before the first dose of administration.
• •5. Patients receiving any medications or substances that are known to be moderate to strong inhibitors or inducers of CYP3A4 and which cannot be discontinued at least 1 week prior to the first dose of administration .
• •6. Patients who have active central nervous system (CNS)or leptomeningeal metastasis. However, participants who are asymptomatic, clinically stable, and did not require steroid therapy at least 4 weeks before the first dose of study treatment are eligible.
• •7. Patients who have cardiovascular and cerebrovascular diseases currently or within the last 6 months, including but not limited to:
• •I. Myocardial infarction; II. Unstable Angina pectoris; III. Cerebrovascular accident; IV. Other acute uncontrolled heart disease; Mean resting corrected QTc interval using the Fridericia formula (QTcF) \> 470 msec/female and \> 450 msec/male; Severe arrhythmias or abnormal cardiac conduction, such as ventricular arrhythmias requiring clinical intervention, degree ii-iii atrioventricular block, etc; Various factors that may increase the risk of QTc prolongation or arrhythmic events, such as heart failure, hypokalemia, congenital long QT syndrome, a family history of a first-degree relative with long QT syndrome or sudden unexplained death before the age of 40, receiving any medication with known QT prolongation; Left ventricular ejection fraction (LVEF) \< 40 % within 4 weeks prior to the first use of the study drug; Hypertension remains uncontrolled after aggressive antihypertensive therapy. Uncontrolled hypertension was defined as systolic blood pressure \> 185 mmHg and/or diastolic blood pressure \> 110 mmHg measured on 3 repetitions at least 10 minutes apart.
• •8. Patients suffering from conditions which are likely to adversely affect gastrointestinal motility (ulcerative disease, uncontrollable nausea, vomiting, diarrhea, or poor absorption syndrome).
• •9. Any evidence of severe or uncontrolled systemic disease, active infection or active bleeding diatheses, including any patient known to have hepatitis B, hepatitis C or human immunodeficiency virus (HIV).
• •10. Patients have uncontrolled pleural, pericardial or abdominal effusion requiring drainage excluding those staying stable for at least two weeks after drainage.
• •11. Patients have active autoimmune disease that requires systemic treatment (immunomodulatory drugs, corticosteroids, or immunomodulatory drugs) in the past 2 years.
• •12. Patients with severely impaired lung functions such as pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, radiation pneumonia and drug-associated pneumonia.
• •13. Patients have allergic reactions to any component of CT-707, toripalimab and gemcitabine, or with history of severe allergic reactions to other monoclonal antibodies or gemcitabine.
• •14. Female patients who are pregnant or breast-feeding, or male or female patients of reproductive potential who are not employing an effective method of birth control.
• •15. Patients with mental disorder, alcohol and/or drug dependence.
• •16. The investigator considers that the subject has a history of serious systemic diseases or other reasons and is not suitable or not willing to participate in this clinical study.