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RC48-ADC in Adjuvant/Salvage Treatment of HER2 Positive Non-muscle-invasive Bladder Cancer

Phase 2
Not yet recruiting
Conditions
Non-muscle Invasive Bladder Cancer
Interventions
Registration Number
NCT05996952
Lead Sponsor
West China Hospital
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.

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.

Recruitment & Eligibility

Status
NOT_YET_RECRUITING
Sex
All
Target Recruitment
77
Inclusion Criteria
  • Be willing and able to provide written informed consent/assent for the trial.
  • Life expectancy ≥12 weeks.
  • 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.
  • Have been treated with adequate BCG therapy and failed (according to 2023 EAU guidelines for NMIBC, for salvage treatment arm).
  • Have elected not to undergo, or are considered ineligible for radical cystectomy, as determined by the treating surgeon.
  • 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.
  • Have a performance status of 0, 1 or 2 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale.
  • Demonstrate adequate organ function.
  • 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.
  • 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
  • Has muscle-invasive (i.e. T2, T3, T4) locally advanced non-resectable or metastatic urothelial carcinoma.
  • Has concurrent extra-vesical (i.e. urethra, ureter or renal pelvis) non-muscle invasive transitional cell carcinoma of the urothelium.
  • 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.
  • 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.).
  • Allergic to study therapy.
  • Has a known additional malignancy that has had progression or has required active treatment in the last five years.
  • Has an active autoimmune disease that has required systemic treatment in past 2 years.
  • Have diseases that may interfere with the study treatment or severe and uncontrolled concomitant diseases.
  • Has had an allogeneic tissue/solid organ transplant.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Salvage RC48-ADCRC48-ADCIn this arm, RC48-ADC is evaluated in patients with HER2-positive non-muscle-invasive bladder cancer who failed BCG treatment as an adjuvant treatment.
Adjuvant RC48-ADCRC48-ADCIn this arm, RC48-ADC is evaluated in patients with HER2-positive high-risk non-muscle-invasive bladder cancer as an adjuvant treatment.
Primary Outcome Measures
NameTimeMethod
12-month recurence-free survival rateFrom 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 rateFrom 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 eventsFrom patient screening to 30 days after end of cycle 6

The type, incidence, relatedness, and severity of adverse events

Secondary Outcome Measures
NameTimeMethod
Progression-free survivalFrom 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

6-month recurence-free survival rateFrom 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

Overall survivalFrom 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 scaleAfter every cycle of treatment and 30 days after end of cycle 6

Assessed by eEuroQoL EQ-5D scale, higher scores mean better outcomes

Recurrence-free survivalFrom 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

Duration of responseFrom time of complete response to up to 60 months

Time from complete response to recurrence of any disease

Trial Locations

Locations (1)

West China Hospital

🇨🇳

Chengdu, Sichuan, China

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