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

A Phase I Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Immunogenicity Profiles of the Recombinant Anti-HER2 and Anti-CD3 Humanized Bispecific Antibody (M802) in HER2-Positive Advanced Solid Tumors

The purpose of this study is to evaluate the safety and tolerability of different doses of M802 in patients with HER2-positive advanced solid tumors, and to determine the dose limiting toxicity (DLT) and the maximum tolerated dose (MTD) so as to provide basis for the recommended phase 2 dose (RP2D).

Inclusion Criteria:

1. Males or females, aged ≥18 years old.

2. 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.

3. 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.

4. 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).

5. Patients must have measurable lesions at baseline according to the RECIST Version 1.1.

6. Patients must have an ECOG performance status (PS) Score of 0-1.

7. Patients must have an expected survival > 12 weeks.

8. Patients must have a baseline left ventricular ejection fraction (LVEF) ≥ 50%.

9. 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.

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

Exclusion Criteria:

1. Patients who had prior treatment with trastuzumab or similar monoclonal drugs within 4 weeks before first dosing of M802.
2. Patients with brain metastasis.
3. Patients who have uncontrollable active infections (Grade ≥ 2 according to CTCAE Version 5.0).
4. Patients with severe respiratory disease who are not suitable for the study at the judgment of investigator.
5. Patients with severe immunosuppression (long-term use of immunosuppressant or glucocorticoid with daily dosage of dexamethasone ≥10 mg).
6. 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.
7. 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.
8. Patients with a history of autoimmune diseases (e.g. inflammatory bowel disease, idiopathic thrombocytopenic purpura, lupus erythematosus, hemolytic anemia, scleroderma, severe psoriasis, rheumatoid arthritis).
9. Patients with severe hyperthyroidism or hypothyroidism.
10. 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.
11. Patients with a history of immunodeficiency, including HIV positive.
12. Patients with Hepatitis b surface antigen test positive or hepatitis c antibody test positive.
13. Patients who have received inoculation of (attenuated) live virus vaccine within 4 weeks before first dosing of M802.
14. Pregnant, lactating women, or females or males who have fertility plan within 12 months.
15. Patients with a previous history of definite neurological or psychiatric disorders, including epilepsy or dementia.
16. 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).
17. 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).