An Open-label, Randomized, Multi-center, Phase III Clinical Study of MRG002 Versus Investigator's Choice of Chemotherapy in the Treatment of Patients With HER2-positive Unresectable Locally Advanced or Metastatic Urothelial Cancer Previously Treated With Platinum-based Chemotherapy and PD-1/PD-L1 Inhibitors
Overview
- Phase
- Phase 3
- Intervention
- Docetaxel Injection
- Conditions
- Advanced or Metastatic Urothelium Cancer
- Sponsor
- Shanghai Miracogen Inc.
- Enrollment
- 290
- Locations
- 1
- Primary Endpoint
- Progression-Free Survival (PFS) by Independent Review Committee (IRC)
- Status
- Recruiting
- Last Updated
- 3 years ago
Overview
Brief Summary
The primary objective of this study is to compare the overall survival (OS) and progression-free survival (PFS) between MRG002 and investigator selected chemotherapy in patients with HER2-positive unresectable locally advanced or metastatic urothelial cancer previously treated with platinum-based chemotherapy and PD-1/PD-L1 inhibitors.
Detailed Description
This study aims to enroll 290 patients. Participants will be randomly assigned to receive treatment of MRG002 or investigator selected chemotherapy in a 1:1 ratio. The efficacy of MRG002 will be assessed by patient's OS, PFS and other indicators as compared to investigator selected chemotherapy. Additionally, this study will assess the pharmacokinetic profile, immunogenicity, safety, tolerability, and treatment compliance 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.
- •Patients who have failed prior platinum-based chemotherapy and PD-1/PD-L1 inhibitors and have have progressive disease or recurrence on or after their most recent therapy.
- •Archival or biopsy tumor specimens should be provided (primary or metastatic).
- •HER2 positive (IHC 3+ or IHC 2+) in the tumor specimens confirmed by central laboratory test.
- •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, Grade 2 hypothyroidism, 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.
- •Patients who have received ADC drugs, or prior taxane, gemcitabine, and pemetrexed for locally advanced or metastatic urothelial cancer; or have received investigational drugs from other clinical trials, chemotherapy, radiotherapy, targeted therapy, or immunotherapy within 4 weeks prior to the first dose; or have received Chinese medicine (herbal medicine) or Chinese patent medicine with anti-tumor indications within 2 weeks prior to the first dose; or have received strong CYP3A4 inhibitors within 2 weeks prior to the first dose or have current requirement of CYP3A4 inhibitors; or had major surgery within 4 weeks prior to the first dose without full recovery or planned surgery within 12 weeks after study treatment.
- •Patients with clinical symptoms such as plural, 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 2.2 mg/kg on Day 1 of every 3 weeks (21-day cycle).
Intervention: Docetaxel Injection
MRG002
MRG002 will be administrated by an IV infusion of 2.2 mg/kg on Day 1 of every 3 weeks (21-day cycle).
Intervention: Paclitaxel Injection
MRG002
MRG002 will be administrated by an IV infusion of 2.2 mg/kg on Day 1 of every 3 weeks (21-day cycle).
Intervention: Gemcitabine Hydrochloride for Injection
MRG002
MRG002 will be administrated by an IV infusion of 2.2 mg/kg on Day 1 of every 3 weeks (21-day cycle).
Intervention: Pemetrexed Disodium Injection
Docetaxel /Paclitaxel /Gemcitabine Hydrochloride /Pemetrexed Disodium Injection
Docetaxel injection will be administered by an IV infusion of 75 mg/m2 on Day 1 of every 3 weeks (21-day cycle); Paclitaxel will be administrated by an IV infusion of 175 mg/m2 on Day 1 of every 3 weeks (21-day cycle). Gemcitabine Hydrochloride will be administrated by an IV infusion of 1000 mg/m2 on Day 1 and Day 8 of every 3 weeks (21-day cycle). Pemetrexed Disodium will be administrated by an IV infusion of 500 mg/m2 on Day 1 of every 3 weeks (21-day cycle).
Intervention: MRG002
Outcomes
Primary Outcomes
Progression-Free Survival (PFS) by Independent Review Committee (IRC)
Time Frame: Baseline to study completion (up to 36 months)
PFS is defined as the duration from the date of randomization to the onset of tumor progression or death of any cause.
Overall Survival (OS)
Time Frame: Baseline to study completion (up to 36 months)
OS is defined as the time from the date of randomization until death of any cause.
Secondary Outcomes
- Disease Control Rate (DCR)(Baseline to study completion (up to 36 months))
- PFS by investigator(Baseline to study completion (up to 36 months))
- Clinical Benefit Rate (CBR)(Baseline to study completion (up to 36 months))
- Objective Response Rate (ORR)(Baseline to study completion (up to 36 months))
- Time to Response (TTR)(Baseline to study completion (up to 36 months))
- Duration of Response (DoR)(Baseline to study completion (up to 36 months))
- Anti-drug antibody (ADA)(Baseline to 7 days after discontinuation of treatment)
- Adverse Events (AEs)(Baseline to 30 days after the last dose of study treatment)
- Neutralizing antibody (NAb)(Baseline to 7 days after discontinuation of treatment)
- Pharmacokinetics (PK) Parameter of MRG002: concentration-time curve(Baseline to 7 days after discontinuation of treatment)