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

A Phase 1, Multicenter, Open-label, Dose-escalation Study to Evaluate the Safety, Tolerability and PK/PD of Recombinant Anti-EpCAM and Anti-CD3 Human-Mouse Chimeric Bispecific Antibody Via Intraperitoneal Infusion in Malignant Ascites

This study is to investigate the safety, tolerability, PK, PD and immunogenicity of multiple ascending doses of M701 administered intraperitoneally to patients with malignant ascites caused by advanced solid tumors.

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

Inclusion Criteria:

1. Males or females, aged > 18 years;

2. Histologically- or cytologically-confirmed advanced solid tumors;

3. 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;

4. Patients who have failed to standard treatment, or who have no standard treatment available that may confer clinical benefit;

5. EpCAM+ tumor cells in ascites fluid;

6. 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;

7. Patients who have recovered from any toxic reaction to previous medications (Grade 0 or 1 based on NCI-CTCAE v5.0);

8. Patients with an ECOG Performance Status score (PS) 0-3;

9. Patients with a life expectancy > 8 weeks;

10. 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;

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

Exclusion Criteria:

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