A Phase I Trial of Simmitinib in Advanced Solid Tumors

Phase I Dose-escalation Trial of Simmitinib for Patients With Advanced Solid Tumors in Therapeutic Failure

This is an open label, multi-center, phase I study of oral Simmitinib in subjects with advanced solid tumors including gastric cancer.

This is an open label, multi-center, phase I study of oral Simmitinib in subjects with advanced solid tumors including gastric cancer [including gastroesophageal cancer], cholangiocarcinoma, lung squamous cell carcinoma, urothelial transitional cell carcinoma, and estrogen-receptor-positive breast cancer patients [ER+], etc. This phase I study will evaluate the safety, tolerability, pharmacokinetics and the preliminary efficacy of the FGFR/KDR/CSF1R multi-target inhibitor Simmitinib.

Inclusion Criteria:

• Voluntary written informed consent of the patient obtained before any study-specific procedure；
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1;
• Patients with histologically/cytologically confirmed diagnosis of advanced solid tumors refractory to standard therapy or for whom no standard therapy exist;
• Adequate washing period from last anti-tumor therapy;
• Measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1;
• The expected survival time for more than 12 weeks;
• Adequate bone marrow, hepatic, renal, pancreas, and coagulation function, Blood phosphorus and calcium in the normal range.

Exclusion Criteria:

• Prior treatment with selective FGFR inhibitors or multi-target kinase Inhibitors with FGFR as the main target;
• Unrecovered from any drug-related adverse event to grade ≤ 1 according to the National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) v.3.0 derived from any previous anti-tumor treatment, excluding alopecia, Pigmentation, or other toxicity with little safety risk for subjects;
• Active Central Nervous System (CNS) metastases (brain or leptomeningeal metastases, etc.);
• Any other history of malignancy within 3 years;
• Congenital coagulation abnormalities. Active bleeding or previous history of massive bleeding (>30ml within 3 months), history of hemoptysis (more than 5ml fresh bleeding within 4 weeks);
• Corneal diseases of clinical significance. There is a history of retinal pigment epithelial detachment or evidence of the presence of retinal pigment epithelial detachment. History of age-related macular degeneration or evidence of age-related macular degeneration exists；
• Subjects with impaired cardiac function or heart disease of clinical significance;
• Pregnant or lactating women.