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

Sponsor

Beijing Mabworks Biotech Co., Ltd. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT03842085

Collaborator

(none)

Enrollment

Location

Arm

43.7

Anticipated Duration (Months)

0.8

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
HER2-positive Recurrent or Metastatic Malignant Solid Tumor	Drug: Recombinant Humanized Bispecific Monoclonal Antibody MBS301	Phase 1

Study Design

Study Type:

Interventional

Anticipated Enrollment :

34 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Apr 11, 2019

Anticipated Primary Completion Date :

Aug 1, 2022

Anticipated Study Completion Date :

Dec 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: MBS301 Drug: Recombinant Humanized Bispecific Monoclonal Antibody MBS301	Drug: Recombinant Humanized Bispecific Monoclonal Antibody MBS301 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. Other Names: MBS301

Arm

Intervention/Treatment

Experimental: MBS301

Drug: Recombinant Humanized Bispecific Monoclonal Antibody MBS301

Drug: Recombinant Humanized Bispecific Monoclonal Antibody MBS301

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.

Other Names:

MBS301

Outcome Measures

Primary Outcome Measures

DLT of MBS301 [up to the third treatment cycle of the last subject was ended (each cycle is 21 days)]
Evaluate the safety of MBS301 and determine the dose limited toxicity (DLT) .
MTD of MBS301 [up to the third treatment cycle of the last subject was ended (each cycle is 21 days)]
Evaluate the safety of MBS301 and determine the maximum tolerated dose (MTD).

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.