A Study of Intravesical FL115 Alone or in Combination With BCG in Non-Muscle Invasive Bladder Cancer

Prior treatment

• 1.Prior Anti-Cancer Treatment History:
• Have previously undergone any of the following NMIBC-related treatments:
  • Received extensive pelvic radiotherapy (involving \>30% of bone marrow) within 2 years prior to the first dose.
  • Received systemic therapy aimed at treating NMIBC (e.g., radiotherapy, chemotherapy, immunosuppressive therapy) within 4 weeks prior to the first dose.
  • Received intravesical instillation aimed at treating NMIBC within 4 weeks prior to the first dose, including intravesical local treatment delivered transurethrally.
  • Underwent TURBT or other surgical procedures targeting bladder lesions within 2 weeks prior to the first dose.
  • 2\. Prior therapies and recovery from related toxicities：
• Systemic immunosuppressive therapy within 4 weeks before first dose, except: ≤10 mg/day prednisone equivalent, local/inhaled/intranasal steroids, adrenal replacement ≤7.5 mg/day prednisone, or single-dose prophylaxis for contrast allergy.
• Prior allogeneic organ or PBSC/bone marrow transplantation. d) Live virus vaccination within 4 weeks prior to first dose. e) Prior ≥ Grade 3 or treatment-discontinuation irAE due to immunotherapy, except controlled hypothyroidism, type 1 diabetes, or limited skin irAEs.
• Unresolved AEs from prior anti-tumor therapy that have not returned to baseline or ≤ Grade 1 (per CTCAE v5.0) prior to first dose, except alopecia, ≤ Grade 2 neuropathy, or controlled hypothyroidism. Other ≤ Grade 2 AEs require PI and sponsor medical review.
  • 3.Medical and Surgical History:
• Discontinuation of prior BCG therapy due to severe adverse events such as sepsis, systemic infection requiring treatment, or urinary incontinence (Phase Ib and II applicable).
• Active or prior autoimmune disease requiring systemic immunosuppressants or corticosteroids.
• History or imaging evidence of active pulmonary TB within 1 year prior to enrollment, or prior TB infection not adequately treated.
• Major surgery within 4 weeks prior to signing informed consent.
  • 4.Infectious Disease History
• Severe infections within 4 weeks before first dose. b) Any history of confirmed active HBV, HCV, HIV, or active tuberculosis infection.
  • 5.Other Conditions

Other illness

• Known or suspected allergy to FL115, its excipients, interleukin-based therapies, or fusion proteins (Grade 3-4), or to BCG/excipients (for Phase Ib/II).
• History or current diagnosis of muscle-invasive (T2-T4), locally advanced (T3/T4, any N), or metastatic bladder cancer.
• Known vesicoureteral reflux or evidence of bladder perforation.
• Active urinary tract infection.
• History of other malignancies within 2 years prior to screening that have shown progression or required active treatment.
• History of severe pulmonary toxicity.
• History of significant cardiovascular disease.
• Any other conditions deemed by the investigator to render the subject unsuitable for participation.

Lab values

• Have previously received IL-2 or IL-15 agonist therapy, including but not limited to rhIL-15 (NCI), ALT-803 (FL-115), and NKTR-214 (Nektar).

Other

• History or evidence of upper urinary tract (kidney, renal pelvis, ureter) or prostatic urethral tumors.
• Post-TURBT complications that preclude intravesical instillation, per investigator judgment.
• Clinically significant polyuria (e.g., 24-hour urine volume \>4000 mL).
• Uncontrolled pleural, pericardial, or peritoneal effusion deemed clinically significant by the investigator (e.g., requiring repeated drainage \>once/month).
• Pregnant or breastfeeding women.
• Known, documented, or suspected substance abuse. Exceptions: Prescribed opioids for pain control or other investigator-approved, medically justified cases (pending sponsor medical lead agreement).

• Male or female subjects aged 18 years or older.
• Histologic confirmation of non-muscle invasive bladder cancer of the transitional cell carcinoma high-grade subtype (mixed histology tumors allowed if transitional cell histology is predominant histology).
• Histologically confirmed presence of BCG-unresponsive CIS (with or without Ta or T1 disease) or histologically confirmed presence of BCG-unresponsive high-grade Ta or T1 disease.
• Absence of resectable disease after transurethral resection (TURBT) procedures (residual carcinoma in situ (CIS) acceptable; patients with T1 tumors must undergo repeat resection and biopsy \[inclusive of muscularis propria\] if initial biopsy did not include muscularis propria). Patients with high-grade Ta and/or T1 disease should have complete resection before study treatment.
• Subjects refuse or are judged by the investigator not suitable for radical cystectomy.
• ECOG score 0-2.
• Expected survival ≥ 2 years (judged by the investigator).
• Adequate organ function.
• Voluntary written informed consent and agree to comply with all protocol-specified procedures and follow-up evaluations.