A Study of M701 (EpCAM and CD3) in Malignant Ascites

To evaluate the safety and tolerability of multiple ascending doses of M701 administered intraperitoneally in patients with malignant ascites.

Inclusion criteria

• Males or females, aged > 18 years;
• Histologically- or cytologically-confirmed advanced solid tumors;
• Patients who require therapeutic paracentesis, defined as at least 1 therapeutic paracentesis (e.g., to relieve abdominal pressure and discomfort) during 4 weeks prior to the baseline paracentesis;
• Patients who have failed to standard treatment, or who have no standard treatment available that may confer clinical benefit;
• EpCAM+ tumor cells in ascites fluid;
• Patients who have received anti-tumor therapy including chemotherapy, hormone therapy, radiotherapy (except local radiotherapy for pain relief) ≥ 2 weeks or received immunotherapy, biological agents ≥ 3 weeks prior to the first dose of study drug;
• Patients who have recovered from any toxic reaction to previous medications (Grade 0 or 1 based on NCI-CTCAE v5.0);
• Patients with an ECOG Performance Status score (PS) 0-3;
• Patients with a life expectancy > 8 weeks;
• Organ function levels must meet the following requirements:

Bone marrow: absolute neutrophil count (ANC) ≥ 1.5 ×10^9/L, platelet count ≥ 80 ×10^9/L, hemoglobin ≥ 9.0 g/dL (without blood transfusion within14 days of the first dose of study drug); Liver: bilirubin ≤ 1.5 x upper limit of normal (ULN), aspartate aminotransferase (AST) and alanine transaminase (ALT) ≤ 3 x ULN ( ≤ 5 x ULN in case of liver metastases); Kidney: serum creatinine ≤1.5 x ULN and estimated glomerular filtration rate (eGFR) ≥ 50 ml/min;

• Patients must understand and voluntarily sign the informed consent form.

Exclusion criteria

• Known to have a history of allergy to the active ingredients of M701; or with a definite history of drug allergy or specific allergy (asthma, rubella, eczema dermatitis);
• Known or suspected hypersensitivity to M701 or similar antibodies;
• Extensive liver metastases (> 70% organ volume comprises malignancy);
• Uncontrolled active infection (CTCAE ≥ Grade 2);
• Serious diarrhea (CTCAE ≥ Grade 2);
• Serious dyspnea requiring oxygen therapy;
• History of auto-immune diseases (e.g. inflammatory bowel disease, idiopathic thrombocytopenic purpura, lupus erythematosus, autoimmune hemolytic anemia, scleroderma, serious psoriasis, rheumatoid arthritis);
• History of acute or chronic pancreatitis;
• Other serious diseases that may prevent patients participation in this trial (such as uncontrolled diabetes mellitus, severe gastrointestinal disorders);
• Cardiac insufficiency, NYHA class III or IV;
• Intestinal obstruction that occurred within 30 days prior to the first dose of study drug;
• Non-drainable ascites;
• Confirmed portal vein obstruction;
• History of immunodeficiency, including positive HIV test;
• Active hepatitis B virus infection or hepatitis C virus infection, positive syphilis antibody test and positive HIV antibody test;
• Pregnant or breastfeeding woman;
• Plan to conceive within six months;
• Previous confirmed history of neurological or mental disorders, including epilepsy and dementia;
• Have received a clinical study active drug treatment within 1 month prior to the first dose of study drug;
• Those that are deemed ineligible for this clinical trial by study personnel.