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

NCT ID: NCT04501744

Last Updated: 2025-07-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 35 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-09-30
• Study Completion Date: 2022-09-30

Brief Summary

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.

Detailed Description

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

Conditions

Malignant Ascites; Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

M701

Patients will undergo a 2-week screening period and a 4-week core treatment period, and eligible patients who complete the core treatment period will receive a cycle of extended treatment (once weekly for 4 weeks) until disease progression or toxicity intolerance.

Group Type: EXPERIMENTAL

Cohort 1 of M701

Intervention Type: DRUG

Patients in Cohort 1 will receive 4 escalating doses (2, 5, 10 and 25 μg) of M701 on Days 1, 8, 15 and 22. The maintenance dose during extended treatment period is 25 μg.

Cohort 2 of M701

Intervention Type: DRUG

Patients in Cohort 2 will receive a starting dose on Day 1 and three infusions at a higher maintenance dose level on Days 8, 15 and 22. The starting dose is 25 μg, and the maintenance dose during core treatment period and extended treatment period is 50 μg.

Cohort 3 of M701

Intervention Type: DRUG

Patients in Cohort 3 will receive a starting dose on Day 1 and three infusions at a higher maintenance dose level on Days 8, 15 and 22. The starting dose is 50 μg, and the maintenance dose during core treatment period and extended treatment period is 100 μg.

Cohort 4 of M701

Intervention Type: DRUG

Patients in Cohort 4 will receive a starting dose on Day 1 and three infusions at a higher maintenance dose level on Days 8, 15 and 22. The starting dose is 100 μg, and the maintenance dose during core treatment period and extended treatment period is 200 μg.

Cohort 5 of M701

Intervention Type: DRUG

Patients in Cohort 5 will receive a starting dose on Day 1 and three infusions at a higher maintenance dose level on Days 8, 15 and 22. The starting dose is 150 μg, and the maintenance dose during core treatment period and extended treatment period is 300 μg.

Cohort 6 of M701

Intervention Type: DRUG

Patients in Cohort 6 will receive a starting dose on Day 1 and three infusions at a higher maintenance dose level on Days 8, 15 and 22. The starting dose is 200 μg, and the maintenance dose during core treatment period and extended treatment period is 400 μg.

Cohort 7 of M701

Intervention Type: DRUG

Patients in Cohort 7 will receive a starting doseon Day 1 and three infusions at a higher maintenance dose level on Days 8, 15 and 22. The starting dose is 250 μg, and the maintenance dose during core treatment period and extended treatment period is 500 μg.

Interventions

Cohort 1 of M701

Patients in Cohort 1 will receive 4 escalating doses (2, 5, 10 and 25 μg) of M701 on Days 1, 8, 15 and 22. The maintenance dose during extended treatment period is 25 μg.

Intervention Type: DRUG

Cohort 2 of M701

Patients in Cohort 2 will receive a starting dose on Day 1 and three infusions at a higher maintenance dose level on Days 8, 15 and 22. The starting dose is 25 μg, and the maintenance dose during core treatment period and extended treatment period is 50 μg.

Intervention Type: DRUG

Cohort 3 of M701

Patients in Cohort 3 will receive a starting dose on Day 1 and three infusions at a higher maintenance dose level on Days 8, 15 and 22. The starting dose is 50 μg, and the maintenance dose during core treatment period and extended treatment period is 100 μg.

Intervention Type: DRUG

Cohort 4 of M701

Patients in Cohort 4 will receive a starting dose on Day 1 and three infusions at a higher maintenance dose level on Days 8, 15 and 22. The starting dose is 100 μg, and the maintenance dose during core treatment period and extended treatment period is 200 μg.

Intervention Type: DRUG

Cohort 5 of M701

Patients in Cohort 5 will receive a starting dose on Day 1 and three infusions at a higher maintenance dose level on Days 8, 15 and 22. The starting dose is 150 μg, and the maintenance dose during core treatment period and extended treatment period is 300 μg.

Intervention Type: DRUG

Cohort 6 of M701

Patients in Cohort 6 will receive a starting dose on Day 1 and three infusions at a higher maintenance dose level on Days 8, 15 and 22. The starting dose is 200 μg, and the maintenance dose during core treatment period and extended treatment period is 400 μg.

Intervention Type: DRUG

Cohort 7 of M701

Patients in Cohort 7 will receive a starting doseon Day 1 and three infusions at a higher maintenance dose level on Days 8, 15 and 22. The starting dose is 250 μg, and the maintenance dose during core treatment period and extended treatment period is 500 μg.

Intervention Type: DRUG

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Wuhan YZY Biopharma Co., Ltd.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jianming Xu

Role: PRINCIPAL_INVESTIGATOR

307 Hospital of PLA

Shixuan Wang

Role: PRINCIPAL_INVESTIGATOR

Tongji Hospital

Locations

The 307th Hospital of Chinese People's Liberation Army

Beijing, Beijing Municipality, China

Tongji Hospital of Tongji Medical College,Huazhong University of Science and Technology

Wuhan, Hubei, China

Countries

China

Other Identifiers

M70101

Identifier Type: -

Identifier Source: org_study_id