A Study of MRG002 in the Treatment of HER2-positive Unresectable Locally Advanced or Metastatic Urothelium Cancer

Study 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.

Official Title
-----------------
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

Conditions
-----------------
Locally Advanced Urothelial Cancer, Metastatic Urothelial Carcinoma

Intervention / Treatment
-----------------
* Drug: MRG002


Participation Criteria
=================
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 1. 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). No severe cardiac dysfunction with left ventricular ejection fraction (LVEF) ≥ 50%. Organ function must meet the basic requirements. Coagulation function must meet the basic requirements. Patients of childbearing potential must take effective contraceptive measures during the treatment and for 6 months after the last dose of treatment. 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 1. History of cirrhosis (decompensated cirrhosis Child-Pugh class B and C). Patients with active autoimmune disease or a history of autoimmune disease, who are using immunosuppressive agents, or systemic hormone therapy and still receiving within 2 weeks prior to enrollment. Received anti-tumor vaccine treatment 4 weeks prior to the first dose or planning to participate in anti-tumor vaccine trials. Female patents with a positive serum pregnancy test or who are breast-feeding or who do not agree to take adequate contraceptive measures during the treatment and for 6 months after the last dose of study treatment. Other conditions inappropriate for participation in this clinical trial, at the discretion of the investigator.

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

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MRG002<br>MRG002 will be administrated by an IV infusion of 2.6 mg/kg on Day 1 of every 3 weeks (21-day cycle). | Drug: MRG002<br>* Administrated intravenously<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) by Independent Review Committee (IRC) | 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. | Baseline to study completion, up to 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ORR by Investigator | ORR is defined as the percentage of patients with CR and PR as assessed by Investigator according to RECIST v1.1. | Baseline to study completion, up to 12 months | 
| Duration of Response (DoR) | DOR is defined as the time from first documented objective response to the first onset of tumor progression or death of any cause. | Baseline to study completion, up to 12 months | 
| Time to Response (TTR) | TTR is defined as the duration from the start of treatment to the first onset of CR or PR in tumor evaluation. | Baseline to study completion, up to 12 months | 
| Disease Control Rate (DCR) | DCR is defined as the percentage of patients who achieve CR, PR, and stable disease (SD) after treatment. | Baseline to study completion, up to 12 months | 
| Progression Free Survival (PFS) | PFS is defined as the duration from the start of treatment to the onset of tumor progression or death of any cause. | Baseline to study completion, up to 12 months | 
| Overall Survival (OS) | OS is defined as the duration from the start of treatment to death of any cause. | Baseline to study completion, up to 12 months | 
| Adverse Events (AEs) | Any reaction, side effect, or untoward event that occurs during the course of the clinical trial whether or not the event is considered related to the study drug. | Baseline to 30 days after the last dose of study treatment | 
| Pharmacokinetics (PK) Parameter of MRG002: concentration-time curve | Concentration-time curve will be depicted based on pharmacokinetics concentration set (PKCS). | Baseline to 30 days after the last dose of study treatment | 
| Incidence of anti-drug antibody (ADA) | The incidence of ADA analysis will be summarized for all patients who received at least one cycle study treatment. | Baseline to 30 days after the last dose of study treatment | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
MRG002, Antibody Drug Conjugate (ADC), HER2, Urothelium Cancer