Toripalimab ± Sequential Intravesical Gemcitabine-Mitomycin C for BCG-Unresponsive/-Intolerant High-Risk NMIBC: Open-Label Randomized Phase 2 Study

Korábbi kezelés

• Low-grade (LG) recurrence during or after BCG therapy.
• Concomitant upper tract urothelial carcinoma, or lymph-node/distant metastasis.
• Systemic chemotherapy, small-molecule targeted therapy, or radiotherapy within 2 weeks before first study treatment.
• Prior immune checkpoint inhibitor therapy.

Más betegség

• Muscle-invasive bladder cancer (T2-T4).
• Contraindications to intravesical instillation, including within 2 weeks after TURBT, bladder perforation, symptomatic urinary tract infection, or gross haematuria.
• Known hypersensitivity or contraindication to gemcitabine, mitomycin C, or toripalimab.
• Ongoing acute or chronic systemic infection, or history of active tuberculosis.
• Other malignancy requiring active treatment.
• Any condition that, in the investigator's judgment, makes participation not in the patient's best interest or could confound study results.
  • Study Population Adults with BCG-unresponsive or BCG-intolerant HR-NMIBC treated at participating centres in China.

Egyéb

• Indwelling ureteral stent or known vesicoureteral reflux.
• Pregnant, planning pregnancy, or breastfeeding women.

• Age ≥18 years; sex: all; signed written informed consent by the participant or legally authorised representative.
• Histologically confirmed high-risk non-muscle-invasive bladder cancer (HR-NMIBC), defined as any T1, high-grade Ta, and/or carcinoma in situ (CIS).
• BCG-intolerant (unable to continue BCG because of severe adverse reactions) or meeting at least one definition of BCG treatment failure:
  • Persistent or recurrent CIS within 12 months after completion of adequate BCG (with or without concomitant NMIBC);
  • Recurrent high-grade Ta/T1 within 6 months after completion of adequate BCG;
  • High-grade T1 at the first evaluation after BCG induction (~3 months);
  • Ta high-grade and/or CIS present or recurrent at ~3 months after receiving ≥5 BCG instillations.
  • Adequate BCG, for the purposes of this protocol, is defined as receipt of at least 5 of 6 induction instillations (maintenance not required).
• ECOG performance status 0-2.
• Adequate organ function per protocol laboratory criteria.
• No intravesical chemotherapy or immunotherapy between the most recent cystoscopy/TURBT and study start; a single immediate postoperative intravesical chemotherapy at the time of the most recent cystoscopy/TURBT is allowed during screening per local practice.
• Willing and able to comply with study procedures.