Comparing MRG002 to standard chemotherapy for advanced urothelial cancer

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

This study is testing whether a new treatment called MRG002 can help people with advanced bladder cancer live longer and feel better compared to standard chemotherapy.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 290 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Shanghai Miracogen Inc. (Industry-sponsored)
• Drugs / interventions: trastuzumab, chemotherapy, immunotherapy
• Locations: 1 site (Beijing, Beijing Municipality)
• Trial ID: NCT05754853 on ClinicalTrials.gov

What this trial studies

This study aims to evaluate the effectiveness of MRG002, an antibody-drug conjugate, compared to investigator-selected chemotherapy in patients with HER2-positive unresectable advanced or metastatic urothelial cancer. A total of 290 participants will be randomly assigned to receive either MRG002 or chemotherapy in a 1:1 ratio. The primary endpoints include overall survival and progression-free survival, along with assessments of safety, tolerability, and pharmacokinetics. The study focuses on patients who have previously undergone platinum-based chemotherapy and PD-1/PD-L1 inhibitors.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 to 75 with HER2-positive unresectable locally advanced or metastatic urothelial cancer who have failed prior treatments.

Not a fit: Patients with HER2-negative tumors or those who have not received prior platinum-based chemotherapy may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new effective option for patients with advanced urothelial cancer who have limited treatment choices.

How similar studies have performed: Other studies have shown promising results with antibody-drug conjugates in similar cancer types, indicating potential for success with this approach.

Eligibility criteria

Inclusion Criteria:

* 1\. Willing to sign the ICF and follow the requirements specified in the protocol.

  2\. Aged 18 to 75 (including 18 and 75), both genders. 3. Expected survival time ≥ 12 weeks. 4. Patients with unresectable locally advanced or metastatic urothelium cancer confirmed by histopathology.

  5\. 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.

  6\. Archival or biopsy tumor specimens should be provided (primary or metastatic).

  7\. HER2 positive (IHC 3+ or IHC 2+) in the tumor specimens confirmed by central laboratory test.

  8\. Patients must have measurable lesions according to the Response Evaluation Criteria in Solid Tumors (RECIST v1.1).

  9\. ECOG performance score 0 or 1. 10. 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).

  11\. Organ function must meet the basic requirements. 12. Patients of childbearing potential must take effective contraceptive measures during the treatment and for 180 days after the last dose of treatment.

Exclusion Criteria:

* 1\. History of hypersensitivity to any component of MRG002 or history of hypersensitivity of ≥ Grade 3 to trastuzumab.

  2\. 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.

  3\. Patients with clinical symptoms such as plural, abdominal or pericardial effusion requiring puncture drainage.

  4\. Patients with central nervous system (CNS) metastasis and/or neoplastic meningitis.

  5\. Any severe or uncontrolled systemic diseases. 6. Patients with poorly controlled heart diseases. 7. Evidence of active infections, including but not limited to Hepatitis B, Hepatitis C, or human immunodeficiency virus (HIV) infection.

  8\. History of other primary malignancies. 9. History of interstitial pneumonia, severe chronic obstructive pulmonary disease, severe pulmonary insufficiency, symptomatic bronchospasm, etc.

  10\. Peripheral neuropathy greater than Grade 1. 11. History of cirrhosis. 12. Patients with active autoimmune disease or a history of autoimmune disease, who are using immunosuppressive agents, or systemic hormone therapy and still receiving them within 2 weeks prior to enrollment.

  13\. Uncontrolled tumor-associated bone pain or urgent spinal cord compression. Patients requiring pain control must have been on a stable treatment regimen for at least 2 weeks at the time of first dose 14. Other conditions inappropriate for participation in this clinical trial, at the discretion of the investigator.

Where this trial is running

Beijing, Beijing Municipality

• Cancer Hospital Chinese Academy of Medical Sciences — Beijing, Beijing Municipality, China (Recruiting)

Study contacts

• Principal investigator: Aiping Zhou, MD — Cancer Institute and Hospital, Chinese Academy of Medical Sciences
• Study coordinator: Program Director

Conditions Advanced or Metastatic Urothelium Cancer; MRG002; Antibody Drug Conjugate; HER2; Urothelium Cancer