Trial Title:
Treatment of Malignant Ascites Caused by Advanced Epithelial Solid Tumors With M701 Bispecific Antibody
NCT ID:
NCT06432296
Condition:
Malignant Ascites
Conditions: Official terms:
Ascites
Study type:
Interventional
Study phase:
Phase 3
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
M701
Description:
Intra-peritoneal infusion of M701 in experimental group (M701 group_
Arm group label:
M701 group
Intervention type:
Procedure
Intervention name:
paracentesis
Description:
Puncture and Draiange of ascites from the peritoneal cavity in both experimental group
and control group
Arm group label:
Control group
Summary:
A Randomized, Controlled, Multi-Center Phase III Clinical Study to Compare the Efficacy
and Safety of Recombinant Anti-EpCAM and Anti-CD3 Human-Mouse Chimeric Bispecific
Antibody (M701) for Intraperitoneal Injection to Paracentesis alone in Patients with
Malignant Ascites Caused by Advanced Epithelial Solid Tumors.
Detailed description:
The phase III study is a controlled, open-label trial designed to assess the
effectiveness and safety of M701 intra-peritoneal infusion for controlling malignant
ascites in patients with Malignant Ascites Caused by Advanced Epithelial Solid Tumors who
are also receiving systemic therapy.
A total of 270 patients with malignant ascites caused by Malignant Ascites Caused by
Advanced Epithelial Solid Tumors will be randomly assigned to two treatment arms in a 2:1
ratio. These patients must have experienced disease progression or intolerance after
receiving at least two lines of systemic therapy.
Both treatment arms will receive the systemic therapy as per the investigator's
instructions. The test arm will receive paracentesis and intra-peritoneal infusion of
M701, while the control arm will receive paracentesis alone.
The primary endpoint of the study is the puncture-free survival, which evaluates the
efficacy of M701 in controlling malignant ascites. Secondary endpoints include the
overall survival (OS),Time to next puncture (TTNP), Patient-reported outcome (PRO) score,
6-month survival rate,1-month and 2-month puncture-free survival rate, safety
profiles,and Anti-m701 antibody (ADA) and Neutralizing antibody (NAb).
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Able to understand and voluntarily sign the written informed consent form;
2. Age ≥18 years and ≤75 years;
3. Histologically or pathologically confirmed epithelial malignant solid
tumors,including: advanced gastric cancer and colorectal cancer that have failed at
least two lines of treatment (treatment failure is defined as progression after
treatment or intolerance after treatment); or platinum-resistant
(platinum-efractory) dvanced ovarian cancer;
4. Pathologically or clinically diagnosed with malignant ascites, and treatment for
malignant ascites is required as judged by the investigator; B-mode ultrasound
confirms that the volume of ascites is moderate or above (moderate or above ascites
is defined as the maximum depth of ascites by B-mode ultrasound in supine position
is ≥ 4.5 cm, or the actual amount of ascites drained is ≥ 1 L;
5. The time interval between the last anti-tumor treatment and Randomization should
meet the following time intervals:
1. Intraperitoneal therapy: The time from the most recent intraperitoneal infusion
therapy to randomization should be ≥ 2 weeks;
2. Systemic treatment: No washout required;
3. AEs should have recovered to Grade ≤ 1 from previous treatment (except for
other adverse reactions (such as alopecia) that do not affect the safety
evaluation of the investigational drug as judged by the investigator according
to NCI-CTCAE V5.0);
6. ECOG PS score of 0 to 2;
7. An expected survival of ≥ 8 weeks;
8. Organ functions must meet the following criteria:
1. Hematology: Absolute neutrophil count (ANC) ≥ 1.5 × 10^9/L, platelets ≥90
×10^9/L, hemoglobin ≥ 85 g/L, and lymphocyte percentage ≥ 10%;
2. Liver function: total bilirubin ≤ 1.5 × upper limit of normal (ULN), aspartate
aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 × ULN (AST and
ALT ≤ 5 × ULN are allowed in case of liver metastasis);
3. Serum albumin ≥ 28 g/L;
4. Renal function: serum creatinine ≤ 1.5 × ULN.
9. Female subjects of childbearing potential should have a negative pregnancy test at
screening; all female subjects of childbearing potential and male subjects should
take adequate contraceptive measures throughout the treatment period and within 6
months after the end of the study.
Exclusion Criteria:
1. Patients with a known history of allergy to M701 or its components; patients with a
known history of allergy to macromolecular ntibody drugs or a history of specific
allergic reactions (asthma, rubella, and eczematous dermatitis);
2. Have previously used M701, or have used antibody drugs targeting EpCAM and/or CD3
within 4 months before the first dose;
3. Patients with central nervous system (CNS) metastases resulting in clinical symptoms
or requiring therapeutic intervention; patients with previously treated brain
metastases can be enrolled if they are asymptomatic and have stable disease as
indicated by imaging examination ≥ 4 weeks before the first dose and do not require
corticosteroids or anticonvulsant therapy;
4. Have undergone major surgery within 4 weeks prior to randomization or plan to
undergo major surgery during the study(excluding exploratory surgery);
5. New or concurrent infection within 14 days prior to randomization that has not been
controlled to clinical stability;
6. Patients with severe respiratory diseases at screening, leading to respiratory
failure or those judged by the investigator to be unsuitable for enrollment;
7. Patients with active autoimmune diseases (e.g., inflammatory bowel
disease,idiopathic thrombocytopenic purpura, lupus rythematosus, autoimmune
hemolytic anemia, scleroderma, severe psoriasis, and rheumatoid arthritis), but
patients with the following conditions are allowed to be screened: type I
diabetes;hypothyroidism that can be controlled by replacement therapy only; skin
diseases that do not require systemic treatment (e.g., vitiligo, psoriasis, and
alopecia);
8. Patients with severe cardiovascular and cerebrovascular diseases at
screening,including cardiac insufficiency (NYHA Class III-IV); acute cardiovascular
and cerebrovascular events (acute myocardial infarction, acute cerebral
infarction,unstable angina, cerebral hemorrhage, etc.) orundergone vascular stenting
within 6 months(Coronary artery stent implantation, intracranial artery stent
implantation,etc.) or pulmonary embolism within the past 6 months; or venous
thrombotic diseases such as venous thrombosis in lower limb within the past month;
9. Patients with complete intestinal obstruction within 30 days prior to
Randomization,or those diagnosed with subileus but judged by the investigator as
unsuitable for participating in the study based on their symptoms, signs, etc., or
those have severe gastrointestinal disease such as gastric/intestinal perforation;
10. Unable to drain the ascites completely due to objective reasons (including ascites
septation) or complicated with chylous ascites;
11. Portal vein embolism or portal hypertension confirmed by examinations;
12. Patients with active chronic hepatitis B [such as positive hepatitis B surface
antigen (HBsAg) and/or positive hepatitis B core antibody (HBcAb), and HBV DNA ≥2000
IU/mL or HBV DNA ≥5000cps/mL], active hepatitis C [such as positive hepatitis C
virus (HCV) antibody and HCV RNA ≥ lower limit of detection], positive human
immunodeficiency virus (HIV) antibody, or active syphilis infection (positive
syphilis-specific antibody and positive syphilis non-specific antibody);
13. Patients with concurrent pleural effusion and clinical symptoms such as chest
tightness and dyspnea, who have received clinical intervention or require clinical
intervention as assessed by the investigator; or those with concurrent moderate to
severe symptomatic pericardial effusion;
14. Pregnant or lactating women;
15. History of definitive neurological or mental disorders that, per the investigator's
judgment, may affect the cognitive function or compliance of the patient, including
unstable epilepsy, dementia, and schizophrenia;
16. Other conditions that the investigator considers unsuitable for participating in
this clinical study.
Gender:
All
Minimum age:
18 Years
Maximum age:
75 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
The First Medical Center of Chinese PLA General Hospital
Address:
City:
Beijing
Zip:
100141
Country:
China
Status:
Recruiting
Contact:
Last name:
Jianming Xu, MD
Phone:
010-68182255
Email:
imxu2003@163.com
Contact backup:
Last name:
Rongrui Liu, MD
Phone:
010-68182255
Email:
liurongrui@hotmail.com
Facility:
Name:
Harbin Medical University Cancer Hospital
Address:
City:
Harbin
Zip:
150081
Country:
China
Status:
Recruiting
Contact:
Last name:
Yanqiao Zhang, PhD
Phone:
0451-85718890
Email:
yanqiaozhang@162.com
Start date:
March 20, 2024
Completion date:
November 11, 2025
Lead sponsor:
Agency:
Wuhan YZY Biopharma Co., Ltd.
Agency class:
Industry
Source:
Wuhan YZY Biopharma Co., Ltd.
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06432296
