This is a multicenter, open-label, Phase I/II clinical study evaluating the safety, efficacy, tolerability, and pharmacokinetic/pharmacodynamic (PK/PD) profiles of HS-10566 in patients with high-risk non-muscle-invasive bladder cancer who are ineligible for or refuse radical cystectomy. The study comprises two distinct phases: a dose exploration phase and a proof-of-concept phase.
Men or women aged greater than or equal to (≥) 18 years.
Signed informed consent form.
Histologically confirmed non-muscle-invasive bladder urothelial carcinoma (i.e., transitional cell carcinoma). Mixed tumor types predominantly consisting of urothelial carcinoma are eligible. Patients diagnosed with neuroendocrine, micropapillary, signet-ring cell, plasmacytoid, or sarcomatoid features are excluded.
Persistent or recurrent CIS within 12 months after adequate BCG therapy, with or without recurrence of high-grade Ta or T1 tumors;
Histopathologically confirmed muscle invasive (pathologic T stage ≥ T2), locally advanced, unresectable, or metastatic urothelial carcinoma.
Urothelial carcinoma outside the bladder (e.g., urethra, ureter, renal pelvis) unless radically resected with no disease recurrence for > 2 years.
Radically treated solid tumor with no activity for ≥5 years before enrollment and low recurrence risk;
adequately treated non-melanoma skin cancer (e.g., basal cell carcinoma, squamous cell carcinoma) or lentigo maligna with no evidence of recurrence;
Parallel
HS-10566
DrugHS-10566 is an intravesical gemcitabine delivery system available in two drug-loaded strengths: 0.3 g gemcitabine and 0.6 g gemcitabine.
HS-10566
DrugHS-10566 is an intravesical gemcitabine delivery system available in two drug-loaded strengths: 0.3 g gemcitabine and 0.6 g gemcitabine.
HS-10566
DrugHS-10566 is an intravesical gemcitabine delivery system available in two drug-loaded strengths: 0.3 g gemcitabine and 0.6 g gemcitabine.
Phase I: RP2D
Phase II Arm 1: overall complete response (CR) rate
Overall CR rate is defined as the percentage of participants achieving a CR at any time post-treatment. It will be measured by determining the percentage of participants without presence of high-grade disease using results from cystoscopy and centrally read urine cytology at any time point.
Phase II Arm 2: disease-free survival (DFS)
DFS will be measured as the time from the date of first dose of study treatment to either the time of the first recurrence of high-risk disease, progression, or death due to any cause, whichever occurs first.
Phase II Arm 3: event-free survival (EFS)
EFS will be measured as the time from the date of first dose of study treatment to either the time of the persistence of CIS after 6 months, the first recurrence of high-risk disease, progression, or death due to any cause, whichever occurs first.
Phase I: Incidence and severity of treatment-emergent adverse events
Incidence of treatment-related adverse events as assessed by Common Terminology Criteria for Adverse Events (CTCAE) v6.0.
Concentrations of Gemcitabine and 2',2' difluorodeoxyuridine (dFdU) in Urine and Plasma
Concentrations of gemcitabine and its metabolite dFdU in urine and plasma will be assessed.
Phase I and Phase II Arm 3: overall complete response (CR) rate
Overall CR rate is defined as the percentage of participants achieving a CR at any time post-treatment. It will be measured by determining the percentage of participants without presence of high-grade disease using results from cystoscopy and centrally read urine cytology at any time point.
Phase I and Phase II Arm 1 and Arm 3: duration of CR (DoR)
DOR is defined from the date of first CR achieved to the date of first evidence of recurrence or progression or death (whichever is earlier) for participants who achieve a CR.
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