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

Exclusion Criteria33

• Prior Anti-Cancer Treatment History:
• 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).
• 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.
• \. Prior therapies and recovery from related toxicities：
• a) 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).
• b) 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.
• c) 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.
• f) 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.
• Medical and Surgical History:
• History or current diagnosis of muscle-invasive (T2-T4), locally advanced (T3/T4, any N), or metastatic bladder cancer.
• History or evidence of upper urinary tract (kidney, renal pelvis, ureter) or prostatic urethral tumors.
• Known vesicoureteral reflux or evidence of bladder perforation.
• Active urinary tract infection.
• 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).
• Post-TURBT complications that preclude intravesical instillation, per investigator judgment.
• Clinically significant polyuria (e.g., 24-hour urine volume \>4000 mL).
• History of other malignancies within 2 years prior to screening that have shown progression or required active treatment.
• Active or prior autoimmune disease requiring systemic immunosuppressants or corticosteroids.
• History of severe pulmonary toxicity.
• History or imaging evidence of active pulmonary TB within 1 year prior to enrollment, or prior TB infection not adequately treated.
• Uncontrolled pleural, pericardial, or peritoneal effusion deemed clinically significant by the investigator (e.g., requiring repeated drainage \>once/month).
• History of significant cardiovascular disease.
• Major surgery within 4 weeks prior to signing informed consent.
• Infectious Disease History
• a) Severe infections within 4 weeks before first dose. b) Any history of confirmed active HBV, HCV, HIV, or active tuberculosis infection.
• Other Conditions
• 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).
• Any other conditions deemed by the investigator to render the subject unsuitable for participation.