Clinical trial NCT04501744: A Study of M701 (EpCAM and CD3) in Malignant Ascites
Official title: A Phase 1, Multicenter, Open-label, Dose-escalation Study to Evaluate the Safety, Tolerability and PK/PD of Recombinant Anti-EpCAM and Anti-CD3 Human-Mouse Chimeric Bispecific Antibody Via Intraperitoneal Infusion in Malignant Ascites
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Malignant Ascites
Cancer
Lead sponsor: Wuhan YZY Biopharma Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2020-08-06
Enrollment: 42
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: To evaluate the safety and tolerability of multiple ascending doses of M701 administered intraperitoneally in patients with malignant ascites.

Eligibility criteria: Inclusion Criteria:

1. Males or females, aged \> 18 years;
2. Histologically- or cytologically-confirmed advanced solid tumors;
3. Patients who require therapeutic paracentesis, defined as at least 1 therapeutic paracentesis (e.g., to relieve abdominal pressure and discomfort) during 4 weeks prior to the baseline paracentesis;
4. Patients who have failed to standard treatment, or who have no standard treatment available that may confer clinical benefit;
5. EpCAM+ tumor cells in ascites fluid;
6. Patients who have received anti-tumor therapy including chemotherapy, hormone therapy, radiotherapy (except local radiotherapy for pain relief) ≥ 2 weeks or received immunotherapy, biological agents ≥ 3 weeks prior to the first dose of study drug;
7. Patients who have recovered from any toxic reaction to previous medications (Grade 0 or 1 based on NCI-CTCAE v5.0);
8. Patients with an ECOG Performance Status score (PS) 0-3;
9. Patients with a life expectancy \> 8 weeks;
10. Organ function levels must meet the following requirements:

    Bone marrow: absolute neutrophil count (ANC) ≥ 1.5 ×10\^9/L, platelet count ≥ 80 ×10\^9/L, hemoglobin ≥ 9.0 g/dL (without blood transfusion within14 days of the first dose of study drug); Liver: bilirubin ≤ 1.5 x upper limit of normal (ULN), aspartate aminotransferase (AST) and alanine transaminase (ALT) ≤ 3 x ULN ( ≤ 5 x ULN in case of liver metastases); Kidney: serum creatinine ≤1.5 x ULN and estimated glomerular filtration rate (eGFR) ≥ 50 ml/min;
11. Patients must understand and voluntarily sign the informed consent form.

Exclusion Criteria:

1. Known to have a history of allergy to the active ingredients of M701; or with a definite history of drug allergy or specific allergy (asthma, rubella, eczema dermatitis);
2. Known or suspected hypersensitivity to M701 or similar antibodies;
3. Extensive liver metastases (\> 70% organ volume comprises malignancy);
4. Uncontrolled active infection (CTCAE ≥ Grade 2);
5. Serious diarrhea (CTCAE ≥ Grade 2);
6. Serious dyspnea requiring oxygen therapy;
7. History of auto-immune diseases (e.g. inflammatory bowel disease, idiopathic thrombocytopenic purpura, lupus erythematosus, autoimmune hemolytic anemia, scleroderma, serious psoriasis, rheumatoid arthritis);
8. History of acute or chronic pancreatitis;
9. Other serious diseases that may prevent patients participation in this trial (such as uncontrolled diabetes mellitus, severe gastrointestinal disorders);
10. Cardiac insufficiency, NYHA class III or IV;
11. Intestinal obstruction that occurred within 30 days prior to the first dose of study drug;
12. Non-drainable ascites;
13. Confirmed portal vein obstruction;
14. History of immunodeficiency, including positive HIV test;
15. Active hepatitis B virus infection or hepatitis C virus infection, positive syphilis antibody test and positive HIV antibody test;
16. Pregnant or breastfeeding woman;
17. Plan to conceive within six months;
18. Previous confirmed history of neurological or mental disorders, including epilepsy and dementia;
19. Have received a clinical study active drug treatment within 1 month prior to the first dose of study drug;
20. Those that are deemed ineligible for this clinical trial by study personnel.

Primary outcomes:
measure: MTD
timeFrame: From the time of the first dose (Day 1) until the forth dosing (Day 28)
measure: Incidence of AEs
timeFrame: 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)
Secondary outcomes:
measure: Area under the curve (AUC) of M701
timeFrame: From the time of first dosing (Day 1) until disease progression or toxicity intolerance (up to 6 months).
measure: Maximum observed concentration (Cmax) of M701
timeFrame: From the time of first dosing (Day 1) until disease progression or toxicity intolerance (up to 6 months).
measure: Minimum observed concentration (Cmin) of M701
timeFrame: From the time of first dosing (Day 1) until disease progression or toxicity intolerance (up to 6 months).
measure: The antibody titer of the neutralizing antibody
timeFrame: From the time of first dosing (Day 1) until disease progression or toxicity intolerance (up to 6 months).
measure: Number of subjects who develop detectable anti-drug antibodies (ADAs)
timeFrame: From the time of first dosing (Day 1) until disease progression or toxicity intolerance (up to 6 months).
measure: Expression levels of CEA
timeFrame: From the time of screening period until disease progression or toxicity intolerance (up to 6 months and 14 days).
measure: Expression levels of CA125
timeFrame: From the time of screening period until disease progression or toxicity intolerance (up to 6 months and 14 days).
measure: Expression levels of CA72-4
timeFrame: From the time of screening period until disease progression or toxicity intolerance (up to 6 months and 14 days).
measure: Expression levels of CA19-9
timeFrame: From the time of screening period until disease progression or toxicity intolerance (up to 6 months and 14 days).
measure: Expression levels of AFP
timeFrame: From the time of screening period until disease progression or toxicity intolerance (up to 6 months and 14 days).
measure: Cytokines
timeFrame: From the time of first dosing (Day 1) until disease progression or toxicity intolerance (up to 6 months).
measure: Counts of Lymphocyte subsets
timeFrame: From the time of first dosing (Day 1) until disease progression or toxicity intolerance (up to 6 months).
measure: Ascites volume
timeFrame: From the time of first dosing (Day 1) until disease progression or toxicity intolerance (up to 6 months).
Other outcomes:
Locations:
city: Beijing
country: China
facility: The 307th Hospital of Chinese People's Liberation Army
state: Beijing
city: Wuhan
country: China
facility: Tongji Hospital of Tongji Medical College,Huazhong University of Science and Technology
state: Hubei
Study officials:
affiliation: 307 Hospital of PLA
name: Jianming Xu
role: PRINCIPAL_INVESTIGATOR
affiliation: Tongji Hospital
name: Shixuan Wang
role: PRINCIPAL_INVESTIGATOR
References: