An Open-label, Single-arm, Multi-center, Phase II Clinical Study of MRG002 in the Treatment of Patients With HER2-positive Unresectable Locally Advanced or Metastatic Urothelium Cancer
Overview
- Phase
- Phase 2
- Intervention
- MRG002
- Conditions
- Locally Advanced Urothelial Cancer
- Sponsor
- Shanghai Miracogen Inc.
- Enrollment
- 58
- Locations
- 36
- Primary Endpoint
- Objective Response Rate (ORR) by Independent Review Committee (IRC)
- Last Updated
- 4 years ago
Overview
Brief Summary
The objective of this study is to assess the safety, efficacy, pharmacokinetics, and immunogenicity of MRG002 as single agent in patients with HER2-positive unresectable locally advanced or metastatic urothelium cancer.
Detailed Description
The study consists of two stages. In Phase IIa, approximately 25 subjects will be enrolled to evaluate the safety and preliminarily efficacy of MRG002. Based on the initial safety and efficacy data obtained from the Phase IIa, the study design of second stage Phase IIb single-arm study either will be continued or the trail will be terminated. If the Phase IIa data support the continuation of the study, in the second stage, approximately an additional 33 subjects will be enrolled to further evaluate the efficacy and safety of MRG002.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Willing to sign the ICF and follow the requirements specified in the protocol.
- •Aged 18 to 75 (including 18 and 75), both genders.
- •Expected survival time ≥ 12 weeks.
- •Patients with unresectable locally advanced or metastatic urothelium cancer confirmed by histopathology.
- •Failed in the prior one or more line of systemic chemotherapy.
- •HER2 positive (IHC 3 + or IHC 2 +) in the tumor specimens confirmed by central laboratory test.
- •Archival or biopsy tumor specimens should be provided (primary or metastatic).
- •Patients must have measurable lesions according to the Response Evaluation Criteria in Solid Tumors (RECIST v1.1).
- •ECOG performance score 0 or
- •Prior anti-tumor treatment-related AEs (NCI CTCAE v5.0 Criteria) have recovered to ≤ Grade 1 (except alopecia, non-clinically significant or asymptomatic laboratory abnormalities).
Exclusion Criteria
- •History of hypersensitivity to any component of MRG002 or history of hypersensitivity of ≥ Grade 3 to trastuzumab.
- •Received radiotherapy, chemotherapy, biotherapy, immunotherapy, or other anti-tumor drugs within 4 weeks prior to the first dose MRG002 treatment.
- •Patients with clinical symptoms such as pleural, abdominal or pericardial effusion requiring puncture drainage.
- •Patients with central nervous system (CNS) metastasis and/or neoplastic meningitis.
- •Any severe or uncontrolled systemic diseases.
- •Patients with poorly controlled heart diseases.
- •Evidence of active infections, including but not limited to Hepatitis B, Hepatitis C, or human immunodeficiency virus (HIV) infection.
- •History of other primary malignancies.
- •History of interstitial pneumonia, severe chronic obstructive pulmonary disease, severe pulmonary insufficiency, symptomatic bronchospasm, etc.
- •Peripheral neuropathy greater than Grade
Arms & Interventions
MRG002
MRG002 will be administrated by an IV infusion of 2.6 mg/kg on Day 1 of every 3 weeks (21-day cycle).
Intervention: MRG002
Outcomes
Primary Outcomes
Objective Response Rate (ORR) by Independent Review Committee (IRC)
Time Frame: Baseline to study completion, up to 12 months
ORR is defined as the percentage of patients with complete response (CR) and partial response (PR) as assessed by Independent Review Committee (IRC) according to RECIST v1.1.
Secondary Outcomes
- ORR by Investigator(Baseline to study completion, up to 12 months)
- Duration of Response (DoR)(Baseline to study completion, up to 12 months)
- Incidence of anti-drug antibody (ADA)(Baseline to 30 days after the last dose of study treatment)
- Disease Control Rate (DCR)(Baseline to study completion, up to 12 months)
- Adverse Events (AEs)(Baseline to 30 days after the last dose of study treatment)
- Pharmacokinetics (PK) Parameter of MRG002: concentration-time curve(Baseline to 30 days after the last dose of study treatment)
- Time to Response (TTR)(Baseline to study completion, up to 12 months)
- Progression Free Survival (PFS)(Baseline to study completion, up to 12 months)
- Overall Survival (OS)(Baseline to study completion, up to 12 months)