Clinical trial NCT06196736: A Study to Evaluate 9MW2821 Versus Chemotherapy in Subjects With Previously Treated Locally Advanced or Metastatic Urothelial Cancer
Official title: An Open-label, Randomized Phase 3 Study to Evaluate 9MW2821 vs Investigator's Choice of Chemotherapy in Subjects With Locally Advanced or Metastatic Urothelial Cancer Who Have Previously Received PD-(L)1 Inhibitor and Platinum-containing Chemotherapy
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Advanced Urothelial Carcinoma
Lead sponsor: Mabwell (Shanghai) Bioscience Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2024-01-09
Enrollment: 432
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study was to compare the antitumor activity of 9MW2821 and chemotherapy in participants with locally advanced or metastatic urothelial cancer previously treated with PD-(L)1 inhibitor and platinum-containing chemotherapy.


Eligibility criteria: Inclusion Criteria:

1. Competent to comprehend, sign, and date an independent ethics committee/institutional review board/research ethics board (IEC/IRB/REB) approved informed consent form.
2. Male or female subjects aged 18 to 75 years (including 18 and 75 years).
3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
4. Histologically confirmed locally advanced or metastatic urothelial cancer, not amenable to resection with curative intent.
5. Subject must have received a platinum containing chemotherapy and PD-(L)1 inhibitor in the metastatic/locally advanced setting. If platinum and/or PD-(L)1 inhibitor was administered in the adjuvant/neoadjuvant setting subject must have progressed during treatment or within 12 months of completion.
6. Subject must have experienced radiographic progression during or after the last treatment regimen.
7. An archival tumor tissue sample or a fresh tissue sample should be provided.
8. Life expectancy of ≥ 12 weeks.
9. Subjects must have measurable disease according to RECIST (version 1.1).
10. Adequate organ functions.
11. Sexually active fertile subjects, and their partners, must agree to use methods of contraception during the study and at least 6 months after termination of study therapy.
12. Subjects are willing to follow study procedures.

Exclusion Criteria:

1. Chemotherapy or radiotherapy within 21 days prior to the first dose of study drug, traditional Chinese medicine with anticancer indication within 14 days prior to the first dose of study drug, use of any investigational drug or device within 28 days prior to the first dose of study drug, received treatment of nectin-4 targeted ADC, received treatment of ADC with MMAE payload, received prior chemotherapy with all available study therapies in the control arm, any strong CYP3A4 inducers/inhibitors within 14 days prior to the first dose of study drug.
2. Preexisting treatment related toxicity Grade ≥ 2 (except alopecia and grade 2 endocrine system toxicity with stable replacement therapy).
3. Major surgery within 28 days prior to first dose of study drug.
4. Hemoglobin A1C (HbA1c) ≥ 8%.
5. Preexisting peripheral neuropathy Grade ≥ 2.
6. Any live vaccines within 28 days before first dose of study drug or during the study.
7. Documented history of clinically significant cardiac or cerebrovascular diseases within 6 months prior to the first dose of study drug.
8. Other severe or uncontrolled disease, i.e. severe respiratory system disease, thromboembolic events, active bleeding or active infection.
9. Central nervous system metastases.
10. History of another malignancy within 3 years before the first dose of study drug. Subjects with cured malignancies are allowed.
11. History of autoimmune disease requiring systemic treatment within 2 years before the first dose of study drug.
12. Has ocular conditions that may increase the risk of corneal epithelium damage.
13. Known sensitivity to any of the ingredients of the investigational product; History of drug abuse or mental illness.
14. Uncontrolled tumor-related bone pain or spinal cord compression. Patients requiring pain medication must be on a stable regimen for at least 2 weeks before the first dose of study drug.
15. Pleural effusion, ascites or pericardial effusion with syptoms or needed drainage.
16. Condition or situation which may put the subject at significant risk.

Primary outcomes:
measure: Progression Free Survival per Blinded Independent Central Review
timeFrame: Up to 3 years
measure: Overall Survival
timeFrame: Up to 3 years
Secondary outcomes:
measure: Objective Response Rate per Blinded Independent Central Review and investigator
timeFrame: Up to 3 years
measure: Duration of Response per Blinded Independent Central Review and investigator
timeFrame: Up to 3 years
measure: Time to response per Blinded Independent Central Review and investigator
timeFrame: Up to 3 years
measure: Disease Control Rate per Blinded Independent Central Review and investigator
timeFrame: Up to 3 years
measure: Progression Free Survival per investigator
timeFrame: Up to 3 years
measure: Incidence of adverse events
timeFrame: Up to 3 years
measure: Incidence of Anti-Drug Antibody (ADA)
timeFrame: Up to 3 years
measure: Mean change from baseline in the European Organisation for Research and Treatment of Cancer (EORTC) 30-item core quality-of-life questionnaire (QLQ-C30）
timeFrame: Up to 3 years
measure: Mean change from baseline in EuroQOL 5-dimension 5-level Questionnaire [EQ-5D-5L] Visual Analog Scale (VAS)
timeFrame: Up to 3 years
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Fudan University Shanghai Cancer Center
state: Shanghai
Study officials:
References: