A Randomized, Controlled, Multi-Center Phase III Clinical Study to Evaluate the Efficacy and Safety of M701 for Intraperitoneal Injection in Patients With Malignant Ascites Caused by Advanced Epithelial Solid Tumors
Overview
- Phase
- Phase 3
- Intervention
- M701
- Conditions
- Malignant Ascites
- Sponsor
- Wuhan YZY Biopharma Co., Ltd.
- Enrollment
- 312
- Locations
- 2
- Primary Endpoint
- PuFS
- Status
- Active, not recruiting
- Last Updated
- 9 months ago
Overview
Brief 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).
Investigators
Eligibility Criteria
Inclusion Criteria
- •Able to understand and voluntarily sign the written informed consent form;
- •Age ≥18 years and ≤75 years;
- •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;
- •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;
- •The time interval between the last anti-tumor treatment and Randomization should meet the following time intervals:
- •Intraperitoneal therapy: The time from the most recent intraperitoneal infusion therapy to randomization should be ≥ 2 weeks;
- •Systemic treatment: No washout required;
- •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);
- •ECOG PS score of 0 to 2;
- •An expected survival of ≥ 8 weeks;
Exclusion Criteria
- •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);
- •Have previously used M701, or have used antibody drugs targeting EpCAM and/or CD3 within 4 months before the first dose;
- •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;
- •Have undergone major surgery within 4 weeks prior to randomization or plan to undergo major surgery during the study(excluding exploratory surgery);
- •New or concurrent infection within 14 days prior to randomization that has not been controlled to clinical stability;
- •Patients with severe respiratory diseases at screening, leading to respiratory failure or those judged by the investigator to be unsuitable for enrollment;
- •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);
- •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;
- •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;
- •Unable to drain the ascites completely due to objective reasons (including ascites septation) or complicated with chylous ascites;
Arms & Interventions
M701 group
M701 will be administered via intra-peritoneal infusion following sufficient drainage of malignant ascites. The treatment regimen consists of a leading dose of 50μg on Day 1, followed by three infusions of the full dose of 400 μg M701 on Days 4, 11, and 18. If well tolerated, patients will continue to receive M701 infusions every 2 weeks as maintenance treatment.Additionally, these patients will receive systemic therapy as determined by the investigator.
Intervention: M701
Control group
Patients in the control group will undergo paracentesis on Day 1 and Day 18. If necessary, they may receive additional paracentesis during this period. Additionally, these patients will receive systemic therapy as determined by the investigator.
Intervention: paracentesis
Outcomes
Primary Outcomes
PuFS
Time Frame: Time from the end of drainage of C1V4 ascites to the start of the next drainage or death (up to 6 months).
Defined as the time from the end of C1V4 ascites drainage to the next drainage (based on the time of puncture) or the time of death is recorded as the PuFS.
Secondary Outcomes
- OS(Time from randomization to death from any cause (up to 6 months).)