Clinical Study of HEC68498 in Patients With Advanced Refractory Solid Tumors

Inclusion Criteria

• •（1）Target subjects
• •1. 18 years of age ≤ age ≤ 70 years of age, regardless of gender;
• •2. Patients with various types of advanced solid tumors confirmed by cytological or histological examination.
• •Dose escalation test phase: including breast cancer, colorectal cancer, neuroendocrine tumors, etc .; Extended trial phase: limited to patients with HR + / HER2-, triple-negative, breast, colorectal, and neuroendocrine tumors, and patients with HR + / HER2- and colorectal cancer need genetic testing (blood and / or tumor tissue) PIK3CA mutations have been confirmed. Patients with triple negative breast cancer need genetic testing (blood and / or tumor tissue) to confirm PIK3CA / PTEN- mutations.
• •3. Requires at least standard treatment failure or no standard treatment. Definition of treatment failure: a. Disease progression during or after treatment must have clear imaging or clinical evidence; b. Withdrawal from treatment due to intolerable response.
• •4. According to the solid tumor evaluation criteria (RECIST 1.1), there is at least one measurable lesion.
• •5. Relieve from previous chemotherapy, hormone therapy, targeted therapy, radiotherapy or surgical treatment of toxic reactions (according to CTCAE v5.0 grading ≤ 1 except hair loss)
• •6. ECOG score is 0 or 1 (see Annex 2 for ECOG score criteria);
• •7. Expected survival time ≥ 12 weeks;
• •(2) The subject must have proper organ function
• •1. Blood routine: absolute neutrophil (ANC) ≥ 1.5 × 109 / L; platelet (PLT) ≥ 75 × 109 / L; hemoglobin (Hb) ≥ 90 g / L; Have received hematopoietic cell colony-stimulating growth factors (eg G-CSF, GM-CSF) or have not received blood transfusions. Erythropoietin or erythropoietin therapy can be maintained if it is used immediately before enrollment.
• •2. Liver function: ALT and AST ≤ 2.5 × ULN (for patients with liver metastases, ALT and AST can be relaxed to ≤ 5.0 × ULN); serum bilirubin ≤ 1.5 × ULN;
• •3. Renal function: serum creatinine ≤ 1.5 × ULN; or creatinine clearance (CrCl) ≥ 60 mL / min calculated according to the Cockcroft-Gault formula:
• •Urine routine urinary protein ≤ 1+; if urinary routine urinary protein ≥ 2+, a 24-hour urine protein quantification is less than 1 g.
• •4. Electrolyte: LLN ≤ blood potassium ≤ ULN;
• •5. Coagulation function: international standardized ratio (INR) ≤ 1.5 × ULN; activated partial thromboplastin time (APTT) ≤ 1.5 × ULN; prothrombin time (PT) ≤ 1.5 × ULN;