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.
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 115
- 试验地点
- 1
- 主要终点
- Puncture-free survival, PuFS
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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).
- •Liver function: Total bilirubin ≤1.5 times the upper limit of normal (ULN), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤3 times ULN (AST and ALT ≤5 times ULN allowed in the presence of liver metastasis).
- •Serum albumin ≥28 g/L. Renal function: Serum creatinine ≤1.5 times ULN.
排除标准
- •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
- •Occurrence of complete intestinal obstruction within 30 days before the first dose, or diagnosis of incomplete intestinal obstruction deemed unsuitable for participation in the trial based on symptoms and signs as determined by the investigator.
- •Inability to adequately drain ascites due to objective reasons (including loculated ascites).
- •Confirmed portal vein obstruction.
- •History of immunodeficiency, including positive HIV test.
- •Active hepatitis B virus infection, active hepatitis C virus infection, active syphilis, or positive HIV antibody.
- •Pregnant or lactating women.
- •Patients with fertility requirements during or within 6 months after treatment.
- •Known history of neurological or psychiatric disorders deemed by the investigator to affect cognitive function or compliance, including unstable epilepsy, dementia, schizophrenia, etc.
研究组 & 干预措施
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.
干预措施: paracentesis (Drug)
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.
干预措施: M701 (Drug)
结局指标
主要结局
Puncture-free survival, PuFS
时间窗: 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
次要结局
- 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))