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

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

Overview

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

Interventions

• 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.

Primary outcome measures

• DLT of MBS301 [Time frame: up to the third treatment cycle of the last subject was ended (each cycle is 21 days)]
• MTD of MBS301 [Time frame: up to the third treatment cycle of the last subject was ended (each cycle is 21 days)]

Secondary outcome measures (12)

• Investigate the pharmacokinetics profile(Cmax) of MBS301 [Time frame: At the end of Cycle 3 (each cycle is 21 days)]
• Investigate the pharmacokinetics profile(AUC) of MBS301 [Time frame: At the end of Cycle 3 (each cycle is 21 days)]
• Investigate the pharmacokinetics profile(Tmax) of MBS301 [Time frame: At the end of Cycle 3 (each cycle is 21 days)]
• Investigate the pharmacokinetics profile(MRT) of MBS301 [Time frame: At the end of Cycle 3 (each cycle is 21 days)]
• Investigate the pharmacokinetics profile(T1/2) of MBS301 [Time frame: At the end of Cycle 3 (each cycle is 21 days)]
• Investigate the pharmacokinetics profile(Vd) of MBS301 [Time frame: At the end of Cycle 3 (each cycle is 21 days)]
• Investigate the pharmacokinetics profile(CL) of MBS301 [Time frame: At the end of Cycle 3 (each cycle is 21 days)]
• Evaluate the immunogenicity of MBS301 [Time frame: 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 [Time frame: up to approximately 2 years]
• Evaluate the duration of response (DoR) of MBS301 [Time frame: up to approximately 2 years]
• Evaluate the disease control rate (DCR) of MBS301 [Time frame: up to approximately 2 years]
• Evaluate the progression free survival (PFS) of MBS301 [Time frame: up to approximately 2 years]

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Henan Cancer Hospital — Zhengzhou

Identifiers

NCT: NCT03842085 · MBS301-CT01

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗