This study is to investigate the safety, tolerability, PK, PD and immunogenicity of multiple ascending doses of M701 administered intraperitoneally to patients with malignant ascites caused by advanced solid tumors.
To evaluate the safety and tolerability of multiple ascending doses of M701 administered intraperitoneally in patients with malignant ascites.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
35
Patients in Cohort 1 will receive 4 escalating doses (2, 5, 10 and 25 μg) of M701 on Days 1, 8, 15 and 22. The maintenance dose during extended treatment period is 25 μg.
Patients in Cohort 2 will receive a starting dose on Day 1 and three infusions at a higher maintenance dose level on Days 8, 15 and 22. The starting dose is 25 μg, and the maintenance dose during core treatment period and extended treatment period is 50 μg.
Patients in Cohort 3 will receive a starting dose on Day 1 and three infusions at a higher maintenance dose level on Days 8, 15 and 22. The starting dose is 50 μg, and the maintenance dose during core treatment period and extended treatment period is 100 μg.
The 307th Hospital of Chinese People's Liberation Army
Beijing, Beijing Municipality, China
Tongji Hospital of Tongji Medical College,Huazhong University of Science and Technology
Wuhan, Hubei, China
MTD
Number of DLTs (dose limiting toxicities) during the first 28 days after the first administrations of study drug in each cohort.
Time frame: From the time of the first dose (Day 1) until the forth dosing (Day 28)
Incidence of AEs
Incidence and severity of AEs, including but not limited to vital signs, physical examination, laboratory tests. All AEs will be classified as Grades 1 through 5 as defined by NCI CTCAE v5.0.
Time frame: From the start of administration to the end of the study or 28 days after the administration is stopped (up to 6 months and 28 days)
Area under the curve (AUC) of M701
The endpoints for assessment of PK of M701 include serum concentrations of M701 at different timepoints after M701 administration.
Time frame: From the time of first dosing (Day 1) until disease progression or toxicity intolerance (up to 6 months).
Maximum observed concentration (Cmax) of M701
The endpoints for assessment of PK of M701 include serum concentrations of M701 at different timepoints after M701 administration.
Time frame: From the time of first dosing (Day 1) until disease progression or toxicity intolerance (up to 6 months).
Minimum observed concentration (Cmin) of M701
The endpoints for assessment of PK of M701 include serum concentrations of M701 at different timepoints after M701 administration.
Time frame: From the time of first dosing (Day 1) until disease progression or toxicity intolerance (up to 6 months).
The antibody titer of the neutralizing antibody
The immunogenicity of M701 will be collected by testing the antibody titer of the neutralizing antibody.
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Patients in Cohort 4 will receive a starting dose on Day 1 and three infusions at a higher maintenance dose level on Days 8, 15 and 22. The starting dose is 100 μg, and the maintenance dose during core treatment period and extended treatment period is 200 μg.
Patients in Cohort 5 will receive a starting dose on Day 1 and three infusions at a higher maintenance dose level on Days 8, 15 and 22. The starting dose is 150 μg, and the maintenance dose during core treatment period and extended treatment period is 300 μg.
Patients in Cohort 6 will receive a starting dose on Day 1 and three infusions at a higher maintenance dose level on Days 8, 15 and 22. The starting dose is 200 μg, and the maintenance dose during core treatment period and extended treatment period is 400 μg.
Patients in Cohort 7 will receive a starting doseon Day 1 and three infusions at a higher maintenance dose level on Days 8, 15 and 22. The starting dose is 250 μg, and the maintenance dose during core treatment period and extended treatment period is 500 μg.
Time frame: From the time of first dosing (Day 1) until disease progression or toxicity intolerance (up to 6 months).
Number of subjects who develop detectable anti-drug antibodies (ADAs)
The immunogenicity of M701 will be assessed by summarizing the number of subjects who develop detectable anti-drug antibodies (ADAs).
Time frame: From the time of first dosing (Day 1) until disease progression or toxicity intolerance (up to 6 months).
Expression levels of CEA
As tumor marker, expression levels of CEA will be tested in each study site.
Time frame: From the time of screening period until disease progression or toxicity intolerance (up to 6 months and 14 days).
Expression levels of CA125
As tumor marker, expression levels of CA125 will be tested in each study site.
Time frame: From the time of screening period until disease progression or toxicity intolerance (up to 6 months and 14 days).
Expression levels of CA72-4
As tumor marker, expression levels of CA72-4 will be tested in each study site.
Time frame: From the time of screening period until disease progression or toxicity intolerance (up to 6 months and 14 days).
Expression levels of CA19-9
As tumor marker, expression levels of CA19-9 will be tested in each study site.
Time frame: From the time of screening period until disease progression or toxicity intolerance (up to 6 months and 14 days).
Expression levels of AFP
As tumor marker, expression levels of AFP will be tested in each study site.
Time frame: From the time of screening period until disease progression or toxicity intolerance (up to 6 months and 14 days).
Cytokines
The levels of pharmacodynamic cytokines will be determined at the PD central laboratory.
Time frame: From the time of first dosing (Day 1) until disease progression or toxicity intolerance (up to 6 months).
Counts of Lymphocyte subsets
Lymphocyte subsets will be determined at the PD central laboratory.
Time frame: From the time of first dosing (Day 1) until disease progression or toxicity intolerance (up to 6 months).
Ascites volume
Ascites volume will be collected before each dose.
Time frame: From the time of first dosing (Day 1) until disease progression or toxicity intolerance (up to 6 months).