Treat Malignant Ascites Caused by Gastrointestinal or Ovarian Cancer With M701 Bispecific Antibody

Malignant Ascites Clinical Trial

Official title:

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.

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT06266091
• Other study ID #: M70102
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: November 24, 2021
• Est. completion date: December 31, 2024

Study information

• Verified date: January 2024
• Source: Wuhan YZY Biopharma Co., Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 80
• Est. completion date: December 31, 2024
• Est. primary completion date: March 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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 0-2. 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.

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 4.

• 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.

Related Conditions & MeSH terms

• Ascites
• Malignant Ascites

Intervention

Drug:
• M701
Intra-peritoneal infusion of M701 combined with system therapy
• paracentesis
paracentesis combined with system therapy

Locations

Country	Name	City	State
China	The First Medical Center of Chinese PLA General Hospital	Beijing	Beijing

Sponsors (1)

Lead Sponsor	Collaborator
Wuhan YZY Biopharma Co., Ltd.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Puncture-free survival, PuFS	The time to the next puncture/drainage or death	From the time of 4th dosing (Day 18) to the next puncture/drainage or death (up to 6 months)
Secondary	objective response rate (ORR) of malignant ascites	The change of precentage of malignant ascites volume from the baseline by the image evaluation	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)
Secondary	Progression-free Survival, PFS	The time to disease progression assessed by the imaging evaluation or toxicity or death	From the time of first dosing (Day 1) until disease progression or toxicity intolerance or death (up to 6 months).
Secondary	Overall survival, OS	The time to death	From the time of first dosing (Day 1) until death (up to 6 months).
Secondary	Quality of Life, QoL	Using the QLQ-C30 Scale to score the quality of life at every visit, which includes 3 parts: global health status(2-14, higher is better), funtional status(16-64, lower is better), symptom scale(12-48, lower is better),	From the time of first dosing (Day 1) until the EOT (up to 6 months).
Secondary	Safety profiles	frequency, relationship and seriousness of adverse events	From the time of first dosing (Day 1) until one month after the EOT (up to 6 months).
Secondary	Positive rate of ADA and Nab in serum	The positive rate of Anti-Drug Antibody (ADA) and Neutralizing antibody (Nab) in the serum during the study	From the time of first dosing (Day 1) until the EOT (up to 6 months).
Secondary	The EpCAM expression in ascites	Measure the count of EpCAM postive cells in the ascites before and after M701 treatment	From the time of first dosing (Day 1) until the EOT (up to 6 months).
Secondary	Trough serum concentration (Ctrough)	The lowest concentration of M701 in the serum in one treatment cycle	6 months (anticipated)
Secondary	Peak serum concentration (Cmax)	The highest concentration of M701 in the serum in one treatment cycle	6 months (anticipated)