Phase I Clinical Study of MBS301 in Treatment of HER2 Positive Recurrent or Metastatic Malignant Solid Tumor

Study Overview
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Brief Summary
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This is a phase I study evaluating the safety and pharmacokinetics of MBS301 after intravenous administration in patients with HER-2 positive recurrent or metastatic malignant solid tumors

Official Title
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Evaluation on Open-Labeled and Dose-Escalation Phase I Clinical Study of Safety and Pharmacokinetics of Recombinant Humanized Bispecific Monoclonal Antibody MBS301 for Injection in Treatment of HER2 Positive Recurrent or Metastatic Malignant Solid Tumor

Conditions
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HER2-positive Recurrent or Metastatic Malignant Solid Tumor

Intervention / Treatment
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* Drug: Recombinant Humanized Bispecific Monoclonal Antibody MBS301


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with HER2-positive recurrent or metastatic malignant solid tumor diagnosed by histopathology or cytology. Patients with any types of malignant solid tumors who have progressed despite standard therapy or are intolerant of standard therapy, or for which no standard therapy exists. Patients should have measurable lesions or immeasurable lesions (according to RECIST 1.1). ECOG physical condition: 0 or 1 point. Expected survival period exceeds 12 weeks. Exclusion Criteria: Absolute neutrophils count (ANC) is less than1.5×109/L and/or blood platelets less than 100 ×109/L and/or hemoglobin less than 9g/dL. Total bilirubin is more than 1.5 ×ULN. Patients without hepatic metastasis, ALT or AST is more than 1.5 ×ULN; Patients with hepatic metastasis, ALT or AST is more than 3 ×ULN. Serum creatinine is more than 1.5 × ULN or estimated creatinine clearance <50 mL/min(according to Cockcroft-Gault). International normalized ratio (INR) is more than 1.5 × ULN or activated partial thromboplastin time (APTT) is more than 1.5 × ULN. Patient has prior treated with anthracyclineswhich accumulated dose is equivalent to adriamycin≥360mg/m2. Patient has been experienced toxic reactions after previous anticancer therapy and has not recovered to Grade 0 or Grade 1 (except for hair loss). Known a history with brain metastasis. Have a history of liver disease of clinical significance. Known to be human immunodeficiency virus (HIV) positive.

Ages Eligible for Study
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Minimum Age: 18 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MBS301<br>Drug: Recombinant Humanized Bispecific Monoclonal Antibody MBS301 | Drug: Recombinant Humanized Bispecific Monoclonal Antibody MBS301<br>* The patients confirming to the eligibility criteria will be assigned to the 8 dose groups based on the sequence of inclusion. MBS301 will be administered intravenousely on day 1 of each 21-day cycle for each patient.The first intravenous infusion for each patient will be last for 90 minutes.It could be changed to 60 minutes for the subsequent infusions if the drug is well tolerated.<br>* Other names: MBS301;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| DLT of MBS301 | Evaluate the safety of MBS301 and determine the dose limited toxicity (DLT) . | up to the third treatment cycle of the last subject was ended (each cycle is 21 days) | 
| MTD of MBS301 | Evaluate the safety of MBS301 and determine the maximum tolerated dose (MTD). | up to the third treatment cycle of the last subject was ended (each cycle is 21 days) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Investigate the pharmacokinetics profile(Cmax) of MBS301 | Maximum Plasma Concentration [Cmax] | At the end of Cycle 3 (each cycle is 21 days) | 
| Investigate the pharmacokinetics profile(AUC) of MBS301 | Area Under the Curve [AUC] | At the end of Cycle 3 (each cycle is 21 days) | 
| Investigate the pharmacokinetics profile(Tmax) of MBS301 | Time for Peak concentration[Tmax] | At the end of Cycle 3 (each cycle is 21 days) | 
| Investigate the pharmacokinetics profile(MRT) of MBS301 | Mean ResidenceTime[MRT] | At the end of Cycle 3 (each cycle is 21 days) | 
| Investigate the pharmacokinetics profile(T1/2) of MBS301 | Half-life[T1/2] | At the end of Cycle 3 (each cycle is 21 days) | 
| Investigate the pharmacokinetics profile(Vd) of MBS301 | Apparent volume of distribution[Vd] | At the end of Cycle 3 (each cycle is 21 days) | 
| Investigate the pharmacokinetics profile(CL) of MBS301 | Clearance[CL] | At the end of Cycle 3 (each cycle is 21 days) | 
| Evaluate the immunogenicity of MBS301 | Anti-drug antibody (ADA) | screening, before the second/third cycle of administration, Cycle 1 day 15, at the end of Cycle 3 (each cycle is 21 days) | 
| Evaluate the objective response rate (ORR)of MBS301 | objective response rate (ORR) | up to approximately 2 years | 
| Evaluate the duration of response (DoR) of MBS301 | duration of response (DoR) | up to approximately 2 years | 
| Evaluate the disease control rate (DCR) of MBS301 | disease control rate (DCR) | up to approximately 2 years | 
| Evaluate the progression free survival (PFS) of MBS301 | progression free survival (PFS) | up to approximately 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HER2-positive, solid tumor, MBS301