Phase 1 Study of FS-1502 in Patients With HER2 Expressed Advanced Solid Tumors and Breast Cancer.

Inclusion Criteria

• •1. Age ≥18 years at the time of study registration (men and women eligible);
• •2. Phase Ia dose-escalation study:
• •Patients with HER2-expressing advanced malignant solid tumors who had failed to standard therapy(including surgery, chemotherapy, radiation therapy or biotherapy) , or can not receive standard therapy, or no standard therapy is available.
• •1. HER2 expression: IHC3+, IHC2+/FISH+
• •2. HER2 expression: IHC1+, IHC2+/FISH-
• •Phase Ib dose-expanded study:
• •Histologically or cytologically confirmed HER2-positive patients with advanced breast cancer who had previously received at least 2 line therapy and had failed anti-HER2 therapy. Details as follows:
• •1. HER2 positive (defined as IHC3+ or IHC2+/FISH+);
• •2. For patients with advanced breast cancer who had previously failed anti-HER2 therapy and had received at least 2-line therapy, postoperative adjuvant therapy which could be considered as a treatment line number if disease progression during treatment and within 12 months after completion of treatment.
• •3. Provide evidence of disease progression or intolerable toxicity as confirmed by the investigator or medical history recorded prior to enrollment.
• •4. The enrollment can be based on written HER2 test report from certified local lab, and if patients had no HER2 test report, they should provide sufficient paraffin sections or fresh tumor tissue specimens which should be sent to the local lab or the central laboratory for testing and confirmation.
• •Pivotal clinical study:
• •Patients with locally advanced or relapsed metastatic breast cancer who have been histologically or cytologically confirmed to be HER2-positive and who have received two or more lines of anti-HER2 therapy in the past. Details as follows:
• •1. Her2-positive patients: Patients with IHC3+ or IHC2+ and FISH positive patients should provide enough tumor tissue samples within 5 years for the central laboratory to confirm HER2 status. Patients with HER2-positive patients are considered to be eligible for inclusion in this study; If the specimens provided are undetectable or are not available, a positive HER2 test from a local laboratory approved by the NMPA may be reported for entrainment.
• •2. Previous treatment with two or more lines of anti-HER2 therapy, neoadjuvant therapy or adjuvant therapy can be used as a treatment line number if the disease progresses during or within 12 months after treatment.
• •3. Evidence of investigator-confirmed or documented disease progression or intolerance of toxicity prior to enrollment.
• •3. The ECOG performance status must be 0 or 1.
• •4. Expected survival for at least 12 weeks.
• •5. Has adequate organ and bone marrow function: absolute neutrophil count (ANC) ≥ 1.0x1E9/L(without colony stimulating factor within 7 days); hemoglobin ≥ 90g/L (without red blood cell infusion within 14 days); platelet count ≥ 100x1E9/L(without thrombopoietin or thrombopoietin receptor agonists within 7 days nor platelet infusion within 14 days); Total bilirubin ≤ 1.5x upper limit normal (ULN), or ≤ 3x ULN if with Gilbert syndrome; aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5x ULN; AST and ALT ≤ 5x ULN if liver metastasis; Serum creatinine \< 1.5x ULN and creatinine clearance ≥ 50mL/min (Cockroft-Gault formula calculation); Serum potassium ≥3.5 mmol/L；albumin ≥ 3g/dL; left ventricular ejection fraction (LVEF) \>50%；urinary protein ≤1+ or 24-hour urinary protein dose \< 1.0g.
• •6. Has at least one non-intracranial measurable lesion by RECIST version 1.1.
• •7. Male or female patients with fertility must agree to use effective contraceptive methods during the study period and within 3 months of the last dose of study therapy, such as dual barrier contraceptive methods, condoms, oral or injectable contraceptives, and intrauterine devices.
• •8. Ability to understand and voluntarily sign written informed consent.