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

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.

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.