A Study of Simmitinib Plus SG001 in Advanced Solid Tumors

Inclusion criteria

• Have fully understood and voluntarily sign the ICF for this study;
• Age of 18-75 years (inclusive);
• Dose escalation phase: patients with histologically or cytologically confirmed inoperable or metastatic advanced solid tumors;
• Dose expansion phase: patients who have failed standard treatment (PD or intolerable toxicity after treatment), have no available standard treatment.According to the previous data, the specific tumor cohort was expanded.
• In the expansion phase, patients should agree to provide tissue specimens for detection of PD-L1 expression levels and/or MSI or dMMR status;
• At least one measurable lesion according to RECIST 1.1;
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) score 0-1;
• Adequate organ function, defined as:

Neutrophil count (ANC) ≥ 1.5 × 10^9/L; Platelet count (PLT) ≥ 100× 10^9/L; Hemoglobin (Hb) ≥ 90 g/L; Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × upper limit of normal (ULN) (≤ 5.0 × ULN for patients with liver metastases); Serum total bilirubin (TBIL) ≤ 1.5 × ULN; Serum creatinine ≤ 1.5 × ULN; Prothrombin time (PT), activated partial thromboplastin time (APTT), international normalized ratio(INR)≤1.5 × ULN; Thyroid Stimulating Hormone (TSH)≤ULN; Left ventricular ejection fraction (LVEF)≥50%; Male and female patients of childbearing age must agree to take effective contraceptive measures during treatment and within 6 months after the last dose of treatment.

Exclusion criteria

• Patients who have previously received any anti-tumor therapy within 4 weeks prior to the first dose;
• Urine protein ≥ ++ and 24 h urine protein > 1.0g at screening period;
• Symptomatic central nervous system (CNS) metastases or meningeal metastases;
• Patients who have previously received any live attenuated vaccine within 4 weeks before the first use of the study treatment or are expected to received any live attenuated vaccine during the study;
• History of allergic reactions attributed to any monoclonal antibody, and uncontrolled history of allergic asthma;
• Patients with other types of malignant tumors within 5 years prior to the screening, except for radically resected, non-recurrent skin basal cell carcinoma, skin squamous cell carcinoma, superficial bladder cancer, cervical cancer in situ, or other carcinoma in situ;
• Patients with any active autoimmune disease requiring systemic therapy within 2 years prior to the first dose;
• Patients with bleeding tendency; active bleeding or a history of heavy bleeding within the past 6 months;
• Presence of any severe and/or uncontrolled disease before starting treatment;
• Any active infection requiring antibiotics or hormones systemic treatment by intravenous infusion within 14 days prior to the first dose;
• Dose expansion phase: Prior systemic therapy with immunosuppressants or immunoagonists targeting PD-1, PD-L1, CTLA-4, etc;
• Dose expansion phase: Prior systemic therapy with Antiangiogenic drugs including Anlotinib, Afatinib , Lenvatinib, Sorafenib and Fruquintinib, etc;