RC48-ADC in Adjuvant/Salvage Treatment of HER2 Positive Non-muscle-invasive Bladder Cancer
Study Details
Study Description
Brief Summary
This study will evaluate the efficacy and safety of intravenous RC48-ADC in adjuvant/salvage treatment of HER2 positive high-risk non-muscle-invasive bladder cancer.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 2 |
Detailed Description
This study is a multicenter phase II study, which aims to evaluate the efficacy and safety of intravenous RC48-ADC in adjuvant/salvage treatment of HER2 positive high-risk non-muscle-invasive bladder cancer.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Adjuvant RC48-ADC In this arm, RC48-ADC is evaluated in patients with HER2-positive high-risk non-muscle-invasive bladder cancer as an adjuvant treatment. |
Drug: RC48-ADC
Patients are treated with RC48-ADC at 2.0 mg/kg as an intravenous infusion over 30-90 minutes (60 minutes is recommended) once every 2 weeks for 12 weeks.
|
| Experimental: Salvage RC48-ADC In this arm, RC48-ADC is evaluated in patients with HER2-positive non-muscle-invasive bladder cancer who failed BCG treatment as an adjuvant treatment. |
Drug: RC48-ADC
Patients are treated with RC48-ADC at 2.0 mg/kg as an intravenous infusion over 30-90 minutes (60 minutes is recommended) once every 2 weeks for 12 weeks.
|
Outcome Measures
Primary Outcome Measures
- 12-month recurence-free survival rate [From treatment initiation to 12 month]
The probability of patients remaining free of high-risk NMIBC or worse for at least 12 months after first dose of RC48-ADC adjuvant treatment
- 3-month pathological complete response rate [From treatment initiation to 3 month]
The proportion of patients are negative for urine cytology and cystoscopy at 3 month after first dose of RC48-ADC salvage treatment
- Adverse events [From patient screening to 30 days after end of cycle 6]
The type, incidence, relatedness, and severity of adverse events
Secondary Outcome Measures
- 6-month recurence-free survival rate [From treatment initiation to 6 month]
The probability of patients remaining free of high-risk NMIBC or worse for at least 6 months after first dose of RC48-ADC adjuvant treatment
- Duration of response [From time of complete response to up to 60 months]
Time from complete response to recurrence of any disease
- Recurrence-free survival [From time of first dose of RC48-ADC adjuvant treatment to up to 60 months]
Time from first dose of RC48-ADC adjuvant treatment to high-risk NMIBC recurrence or worse
- Progression-free survival [From time of first dose of RC48-ADC treatment to up to 60 months]
Time from first dose of RC48-ADC treatment to progression to higher stage or death
- Overall survival [From time of first dose of RC48-ADC treatment to up to 60 months]
Time from first dose of RC48-ADC treatment to death from any cause
- Quality of life assessed by EQ-5D scale [After every cycle of treatment and 30 days after end of cycle 6]
Assessed by eEuroQoL EQ-5D scale, higher scores mean better outcomes
Eligibility Criteria
Criteria
Inclusion Criteria:
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Be willing and able to provide written informed consent/assent for the trial.
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Life expectancy ≥12 weeks.
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Have a histologically-confirmed diagnosis of high-risk non-muscle-invasive (according to 2023 NCCN guidelines for bladder cancer) transitional cell carcinoma of the bladder. Subjects with tumors of mixed transitional/non-transitional cell histology are allowed, but transitional cell carcinoma must be the predominant histology.
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Have been treated with adequate BCG therapy and failed (according to 2023 EAU guidelines for NMIBC, for salvage treatment arm).
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Have elected not to undergo, or are considered ineligible for radical cystectomy, as determined by the treating surgeon.
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Have tumor tissues for HER2 IHC evaluation and have a HER2 expression score of HER2 2+ or HER2 3+ reviewed by an independent pathologist at the central laboratory.
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Have a performance status of 0, 1 or 2 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale.
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Demonstrate adequate organ function.
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Female subjects of childbearing potential must have a negative urine or serum pregnancy test within 7 days prior to receiving the first dose of study medication.
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Male subjects of childbearing potential (Section 5.7.2) must agree to use an adequate method of contraception starting with the first dose of study therapy through 6 months after the last dose of study therapy.
Exclusion Criteria:
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Has muscle-invasive (i.e. T2, T3, T4) locally advanced non-resectable or metastatic urothelial carcinoma.
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Has concurrent extra-vesical (i.e. urethra, ureter or renal pelvis) non-muscle invasive transitional cell carcinoma of the urothelium.
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Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment.
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Has undergone any intervening intravesical chemotherapy or immunotherapy from the time of most recent cystoscopy/TURBT to starting trial treatment. (Note: A single dose of intravesical treatment given as part of the most recent cystoscopy/TURBT, during the screening period, such as with chemotherapy as per local / regional practices, is acceptable.).
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Allergic to study therapy.
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Has a known additional malignancy that has had progression or has required active treatment in the last five years.
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Has an active autoimmune disease that has required systemic treatment in past 2 years.
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Have diseases that may interfere with the study treatment or severe and uncontrolled concomitant diseases.
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Has had an allogeneic tissue/solid organ transplant.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | West China Hospital | Chengdu | Sichuan | China | 610041 |
Sponsors and Collaborators
- West China Hospital
- RemeGen Co., Ltd.
Investigators
- Principal Investigator: Hao Zeng, West China Hospital
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 2023(24)