A Study of M802 (HER2 and CD3) in HER2-Positive Advanced Solid Tumors

Inclusion criteria

• Males or females, aged ≥18 years old.
• Patients must have a diagnosis of histologically or cytologically confirmed metastatic advanced solid tumor with failure to standard treatment and who have no available therapy that may confer clinical benefit. Patients with HER2-positive metastatic breast cancer should have received standard anti-HER2 therapies.
• HER2 expression status report should be provided during the screening period with fluorescence in-situ hybridization (FISH) or Chromogenic in situ hybridization (CISH) test positive, or immunohistochemistry IHC 3+, or immunohistochemistry IHC 2+ and confirmed by amplification of FISH or CISH.
• Patients must have stopped anti-tumor treatment for at least 4 weeks prior to the first dose of M802. The anti-tumor treatment includes chemotherapy, immunotherapy, targeted therapy, endocrine therapy, and radiotherapy (except for local radiation therapy for alleviating pain, at least 14 days after end of treatment).
• Patients must have measurable lesions at baseline according to the RECIST Version 1.1.
• Patients must have an ECOG performance status (PS) Score of 0-1.
• Patients must have an expected survival > 12 weeks.
• Patients must have a baseline left ventricular ejection fraction (LVEF) ≥ 50%.
• Patients must have adequate haematological and organ functions as indicated by the following laboratory values:

Haematological: Absolute Neutrophil Count (ANC) ≥ 1.5 ×10^9/L; Blood Platelet Count (BPC) ≥ 80 ×10^9/L; Hemoglobin ≥ 9.0 g/dL (No blood transfusions within 14 days).

Hepatic: Bilirubin ≤ 1.5 × upper limit of normal (ULN); AST and ALT ≤ 2.5 × ULN (AST, ALT ≤ 5 × ULN is allowed when there is liver metastasis).

Renal: Serum creatinine ≤ 1.5 × ULN.

• Patients must understand and voluntarily agree to participate by signing written informed consent.

Exclusion criteria

• Patients who had prior treatment with trastuzumab or similar monoclonal drugs within 4 weeks before first dosing of M802.
• Patients with brain metastasis.
• Patients who have uncontrollable active infections (Grade ≥ 2 according to CTCAE Version 5.0).
• Patients with severe respiratory disease who are not suitable for the study at the judgment of investigator.
• Patients with severe immunosuppression (long-term use of immunosuppressant or glucocorticoid with daily dosage of dexamethasone ≥10 mg).
• Patients who have other malignant tumors in the past 5 years, except the complete cured cervical carcinoma in situ or basal cell or squamous cell carcinoma.
• Patients with a history of serious cardiovascular disease, including receiving coronary artery bypass grafts or coronary stenting, occurrence of myocardial infarction, congestive heart failure within 6 months, or a history of unstable angina, uncontrolled severe hypertension or arrhythmia requiring medication.
• Patients with a history of autoimmune diseases (e.g. inflammatory bowel disease, idiopathic thrombocytopenic purpura, lupus erythematosus, hemolytic anemia, scleroderma, severe psoriasis, rheumatoid arthritis).
• Patients with severe hyperthyroidism or hypothyroidism.
• Patients with metabolic diseases such as uncontrolled diabetes, severe gastrointestinal bleeding, severe diarrhea (Grade ≥ 2 according to CTCAE Version 5.0), or severe gastrointestinal obstruction requiring intervention.
• Patients with a history of immunodeficiency, including HIV positive.
• Patients with Hepatitis b surface antigen test positive or hepatitis c antibody test positive.
• Patients who have received inoculation of (attenuated) live virus vaccine within 4 weeks before first dosing of M802.
• Pregnant, lactating women, or females or males who have fertility plan within 12 months.
• Patients with a previous history of definite neurological or psychiatric disorders, including epilepsy or dementia.
• Patients who participated in clinical studies of other drugs within 4 weeks prior to first dosing of M802 (using last dosing of other drug's clinical studies as end).
• Patients with adverse reactions from previous treatment haven't recovered to grade 1 according to CTCAE Version 5.0 (except for residual effect on hair loss).