Safety, Tolerability and Pharmacokinetic Profile of M108 Monoclonal Antibody in Patients With Advanced Unresectable Solid Tumors in China

Study Overview
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Brief Summary
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M108 is a monoclonal antibody specific for gastric and gastroesophageal adenocarcinomas. The aim of this phase I study is to establish safety and Tolerability of different Dosage regimen in patients With Advanced Unresectable Solid Tumors in China.

Official Title
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A Phase I, Multi-center, Open-label, Single-dose Escalation and Expansion, Dose Escalation and Expansion Combination With Chemotherapy Study Evaluating the Safety, Tolerability and Pharmacokinetic Profile of M108 Monoclonal Antibody in Patients With Advanced Unresectable Solid Tumors in China

Conditions
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Advanced Unresectable Solid Tumors

Intervention / Treatment
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* Drug: M108
* Drug: M108


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written informed consent. Advanced Unresectable solid tumors proven by histology At least 1 measurable site of the disease according RECIST 1.1 criteria ECOG performance status (PS) 0-1 Life expectancy > 3 months Age ≥ 18 years and ≤75 years Adequate haematological function; absolute neutrophil count ≥1.5 x 109/L; white blood cell count ≥3.0 x 109/L; platelets ≥100 x 109/L; haemoglobin ≥9 g/dL. Adequate coagulation function; international normalized ratio ( INR) ≤ 1.5 x upper limit of normal (ULN), or activated partial thromboplastin time (APTT) ≤ 1.5 x ULN. Adequate hepatic function; bilirubin ≤1.5 x ULN, aspartate aminotransferase (AST), and alanine aminotransferase (ALT) ≤2.5 x ULN. Adequate renal function; creatinine ≤1.5 x ULN, or reatinine clearance rate ≥60 mL/minute calculated. Exclusion Criteria: Previous received or planned to be vaccinated with 2019-nCoV vaccine or other vaccines within 3 months prior to the start of study treatment or during the study or within 3 months after the end of the study; Previous radiotherapy within 4 weeks prior to the start of study treatment. (if palliative radiotherapy was given to bone metastatic side peripherally and the patient recovered from acute toxicity was allowed). Previous anti-tumor therapy within 4 weeks prior to the start of study treatment. Previous major operation within 8 weeks prior to the start of study treatment. Prior severe allergic reaction or intolerance to a monoclonal antibody, including humanised or chimeric antibodies. Symptomatic cerebral metastases. Uncontrolled or severe illness. Known human immunodeficiency virus infection or known symptomatic hepatitis Other clinically significant disease which may have adversely affected the safe delivery of treatment within this study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dose Escalation Cohort<br>Monotherapy: Five dose levels of M108 will be tested according to an accelerated titration method followed by a conventional 3 + 3 study design. Combined with chemotherapy: Three dose levels of M108 will be tested by a conventional 3 + 3 study design. The dose-limiting toxicity (DLT) will be assessed from the first administration to the end of the first cycle (21 days). | Drug: M108<br>* Monotherapy: Accelerated titration method, IV infusion Q3W; Conventional 3 + 3 study design, IV infusion Q3W. (21-day cycles) Combined with chemotherapy: Conventional 3 + 3 study design, IV infusion Q3W. (21-day cycles)<br>* Other names: Chemotherapy;|
| Experimental: Dose Expansion Cohort<br>Once the effective dose has been determined, 1 2 expansion cohorts will be opened to evaluate the efficacy and safety of the selected dose. | Drug: M108<br>* IV infusion Q3W. (21-day cycles)<br>* Other names: Chemotherapy.;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of adverse events | defined by the Common Terminology Criteria for Adverse Events version 5.0 (CTCAE V5.0) | From enrollment until 28+7 days after the last dose | 
| Maximum Tolerated Dose | MTD | 21 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum measured plasma concentration of M108 | Cmax | From enrollment until 28 days after the last dose | 
| Time to maximum plasma concentration of M108 | Tmax | From enrollment until 28 days after the last dose | 
| Half-life of M108 | T1/2 | From enrollment until 28 days after the last dose | 
| Immunogenicity profile of M108 | Blood samples will be collected from subjects post treatment for assessment to detect the presence of anti-drug antibodies(ADA). | From enrollment until 28 days after the last dose | 
| Objective Response Rate | ORR | From first dose to disease progression , death or end of study，an average of 1 year | 
| Progression free survival | PFS | From first dose to disease progression , death or end of study，an average of 1 year |