A Phase II, Randomized, Open-label, Controlled, Multicenter Study to Evaluate the Efficacy and Safety of M701 Combined With Systemic Therapy in Patients With Malignant Ascites Caused by Gastrointestinal or Ovarian Cancer.
Overview
- Phase
- Phase 2
- Intervention
- M701
- Conditions
- Malignant Ascites
- Sponsor
- Wuhan YZY Biopharma Co., Ltd.
- Enrollment
- 115
- Locations
- 1
- Primary Endpoint
- Puncture-free survival, PuFS
- Status
- Completed
- Last Updated
- 9 months ago
Overview
Brief Summary
A Phase II, Randomized, Open-label, Controlled, Multicenter Study to Evaluate the Efficacy and Safety of M701 in treating Patients with Malignant Ascites Caused by Gastrointestinal or Ovarian Cancer combined with Systemic Therapy.
Detailed Description
The phase II 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 gastrointestinal and ovarian cancer who are also receiving systemic therapy. A total of 80 patients with malignant ascites caused by gastrointestinal or ovarian cancer will be randomly assigned to two treatment arms in a 1:1 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, but the test arm will additionally receive M701 intra-peritoneal infusion, while the control arm will undergo paracentesis only. The primary endpoint of the study will be the puncture-free survival, which evaluates the efficacy of M701 in controlling malignant ascites. Secondary endpoints include the objective response rate (ORR) of malignant ascites, progression-free survival (PFS), overall survival (OS), quality of life (QOL), and safety profiles. The number of EpCAM-positive cells in the malignant ascites will be measured using flow cytometry before and after treatment with M701.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Able to understand and voluntarily sign the written informed consent form.
- •Histologically or pathologically confirmed epithelial malignancies, including advanced gastric cancer or colorectal cancer that has failed at least two lines of treatment, or platinum-resistant advanced ovarian cancer, primary peritoneal carcinoma, or fallopian tube carcinoma.
- •Clinical diagnosis of malignant ascites with a moderate or higher amount of ascites. Moderate or higher is defined as having a volume of ascites ≥1L based on CT assessment or actual drainage of ≥1L.
- •The time interval between the most recent anti-tumor treatment and the first dose of M701 must meet the following criteria:
- •Intraperitoneal treatment: ≥2 weeks since the most recent intraperitoneal treatment.
- •Adverse events (AEs) from previous treatments have recovered to grade ≤1 (excluding other AEs deemed by the investigator not to affect the safety of the study drug, such as hair loss).
- •Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-
- •Estimated survival time ≥8 weeks.
- •Organ function levels must meet the following requirements:
- •Hematology: Absolute neutrophil count (ANC) ≥1.5 × 10\^9/L, platelets ≥80 × 10\^9/L, hemoglobin ≥8.5 g/dL, lymphocyte ratio (lymphocyte count/leukocyte count) ≥10% (without transfusion within 14 days).
Exclusion Criteria
- •Patients who have previously received M701 or any antibody-based drugs targeting EpCAM and/or CD3 within the 4 months prior to the first dose.
- •Patients with microsatellite instability-high (MSI-H)/deficient mismatch repair (dMMR) colorectal cancer who have not previously received immunotherapy.
- •Patients who have undergone major surgery within the 4 weeks prior to the first dose.
- •Patients with extensive liver metastases (tumor volume occupying approximately \>70% of total liver volume).
- •Active infections requiring intravenous antibiotics within 14 days before the first dose.
- •Severe diarrhea (CTCAE grade ≥2).
- •Severe respiratory distress requiring oxygen therapy.
- •Active autoimmune diseases, except for the following conditions that are allowed for screening: type 1 diabetes, controlled hypothyroidism with replacement therapy only, skin diseases that do not require systemic treatment。
- •Other severe medical conditions that may limit the patient's participation in the trial。
- •Impaired cardiac function with New York Heart Association (NYHA) class 3 or
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
Puncture-free survival, PuFS
Time Frame: From the time of 4th dosing (Day 18) to the next puncture/drainage or death (up to 6 months)
The time to the next puncture/drainage or death
Secondary Outcomes
- Overall survival, OS(From the time of first dosing (Day 1) until death (up to 6 months).)
- objective response rate (ORR) of malignant ascites(From the time of 4th dosing (Day 18) to the next puncture/drainage or death (up to 180 days)re/drainage or death (up to 6 months))
- Positive rate of ADA and Nab in serum(From the time of first dosing (Day 1) until the EOT (up to 6 months).)
- The EpCAM expression in ascites(From the time of first dosing (Day 1) until the EOT (up to 6 months).)
- Progression-free Survival, PFS(From the time of first dosing (Day 1) until disease progression or toxicity intolerance or death (up to 6 months).)
- Quality of Life, QoL(From the time of first dosing (Day 1) until the EOT (up to 6 months).)
- Safety profiles(From the time of first dosing (Day 1) until one month after the EOT (up to 6 months).)
- Trough serum concentration (Ctrough)(6 months (anticipated))
- Peak serum concentration (Cmax)(6 months (anticipated))