A Study of HS-10566 in Patients With High-risk Non-muscle-invasive Bladder Cancer Who Are Ineligible for or Refuse Radical Cystectomy

A Phase I/II Clinical Study Evaluating the Safety, Efficacy, Tolerability, and Pharmacokinetics of HS-10566 in Patients With High-risk Non-muscle-invasive Bladder Cancer Who Are Ineligible for or Refuse Radical Cystectomy

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.

Study Overview

• Status: Not yet recruiting
• Conditions: High-risk Non-muscle-invasive Bladder Cancer
• Intervention / Treatment: Drug: HS-10566

Detailed Description

The study will commence with a dose exploration phase employing a safety lead-in approach. Treatment cycles are 28 days in duration, with investigational product administration continuing for 2 years or until disease progression or fulfillment of other treatment discontinuation criteria. Each dose level will enroll 6 participants for dose-limiting toxicity (DLT) assessment to evaluate the tolerability, safety, and PK/PD profiles of HS-10566. The Safety Review Committee (SRC) will determine subsequent dose levels for exploration via joint review.

Following identification of safe dose levels in the exploration phase, one dose cohort will advance to the proof-of-concept phase, with each cohort enrolling up to 50 participants to further assess therapeutic efficacy and safety.

• Study Type: Interventional
• Enrollment (Estimated): 180
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Zhisong HE, M.D(Doctor of Medicine); Phone Number: (+86) 13910688432; Email: wyj7074@sohu.com
• Study Contact Backup: Name: Hongqian GUO, M.D(Doctor of Medicine); Phone Number: (+86) 025 83106666; Email: gymwpi@126.com

Study Locations

• China
  • Beijing, China, 100034
    • Peking University First Hospital
    • Contact: Zhisong HE, M.D(Doctor of Medicine); Phone Number: (+86) 13910688432; Email: wyj7074@sohu.com
  • Nanjing, China, 210008
    • Nanjing Drum Tower Hospital
    • Contact: Hongqian GUO, M.D(Doctor of Medicine); Phone Number: (+86) 025 83106666; Email: gymwpi@126.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Men or women aged greater than or equal to (≥) 18 years.
2. Signed informed consent form.
3. 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.

4. Patients with non-muscle-invasive bladder cancer (NMIBC) who have undergone prior transurethral resection of bladder tumor (TURBT) and who refuse or are ineligible for radical cystectomy, and meet one of the following two populations:

   1. Patients with high-risk non-muscle-invasive bladder cancer (HR-NMIBC) who are unresponsive to Bacillus Calmette-Guérin (BCG) therapy after prior TURBT, and who refuse or are ineligible for radical cystectomy. BCG unresponsive is defined as occurrence of any one of the following in NMIBC patients after adequate BCG therapy (at least 5 full dose inductions and at least 2 maintenance instillations of BCG):

      • Persistent or recurrent CIS within 12 months after adequate BCG therapy, with or without recurrence of high-grade Ta or T1 tumors;
      • Recurrence of high-grade Ta/T1 tumors within 6 months after adequate BCG therapy (disease-free);
      • Recurrence of high-grade tumors at the first assessment during maintenance therapy after adequate BCG induction.

   2. Patients who have not received BCG therapy after prior TURBT, including the following three scenarios:

      • NMIBC patients who failed intravesical chemotherapy, and who refuse or are ineligible for repeat postoperative intravesical chemotherapy or BCG instillation by the investigator.
      • HR-NMIBC patients who have not received BCG therapy after TURBT, and who refuse or are ineligible for BCG instillation as determined by the investigator. Ineligibility for BCG includes, but is not limited to: active tuberculosis, severe hematuria, recent traumatic catheterization, symptomatic urinary tract infection, immunodeficiency or impairment (e.g., AIDS, patients receiving immunosuppressants or radiotherapy), BCG hypersensitivity, etc.
      • HR-NMIBC patients who received prior BCG therapy but discontinued treatment for more than 3 years before enrollment.

5. Participants must have undergone TURBT within 12 weeks prior to signing informed consent and meet the following criteria:

   1. For papillary lesions (Ta and T1 stages): complete resection of all visible papillary lesions, with negative urine cytology (including atypical findings).
   2. For patients with CIS: residual unresectable CIS lesions are permitted.
6. Sufficient bone marrow reserve and adequate hepatic/renal function.
7. Eastern Cooperative Oncology Group (ECOG) performance status score 0-1.

Exclusion Criteria:

1. Histopathologically confirmed muscle invasive (pathologic T stage ≥ T2), locally advanced, unresectable, or metastatic urothelial carcinoma.
2. Urothelial carcinoma outside the bladder (e.g., urethra, ureter, renal pelvis) unless radically resected with no disease recurrence for > 2 years.

3. History of other primary solid tumors, except:

   1. Radically treated solid tumor with no activity for ≥5 years before enrollment and low recurrence risk;
   2. adequately treated non-melanoma skin cancer (e.g., basal cell carcinoma, squamous cell carcinoma) or lentigo maligna with no evidence of recurrence;
   3. adequately treated carcinoma in situ (e.g., cervical, ductal carcinoma in situ of breast) with no evidence of recurrence.

4. Has received or is receiving any of the following treatments:

   1. Regular intravesical chemotherapy (gemcitabine, pirarubicin, mitomycin, etc.) or BCG instillation intolerance following TURBT/bladder biopsy before enrollment.
   2. Pelvic radiotherapy within 4 weeks prior to first study treatment. Patients with last radiotherapy >4 weeks prior and no confirmed radiation cystitis may be enrolled.
   3. Major surgery (TURBT is not considered major surgery) within 4 weeks before first study treatment, or incomplete recovery from postoperative complications.
   4. Systemic chemotherapy, small-molecule targeted therapy, or investigational therapy within 4 weeks before first study treatment.
5. Residual toxicity ≥ Grade 2 per CTCAE version 6.0 from prior therapy (surgery, intravesical instillation, etc.), except alopecia, pigmentation.
6. Bladder or urethral anatomical features that may interfere with HS-10566 implantation, retention, or removal (e.g., urethral stricture, bladder diverticulum, total urinary incontinence, bladder perforation).
7. Current or history of clinically significant polyuria (24-hour urine output >4000 mL).
8. Requirement for long-term indwelling urinary catheter during study treatment (e.g., urinary obstruction).
9. Intermittent catheterization for clinical indications is allowed.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1:Bacillus Calmette-Guerin (BCG)-unresponsive participants with carcinoma in situ.; HS-10566 is placed into the bladder through a urinary placement catheter in participants with CIS, with or without papillary disease, on Day 1 and will be dosed Q4W for up to the first 24 weeks (6 months), then every 12 weeks through Week 96 (Year 2).	Drug: HS-10566; HS-10566 is an intravesical gemcitabine delivery system available in two drug-loaded strengths: 0.3 g gemcitabine and 0.6 g gemcitabine.
Experimental: Arm 2: BCG-unresponsive participants with high-risk papillary-only disease; HS-10566 is placed into the bladder through a urinary placement catheter in participants with papillary disease only, on Day 1 and will be dosed Q4W for up to the first 24 weeks (6 months), then every 12 weeks through Week 96 (Year 2).	Drug: HS-10566; HS-10566 is an intravesical gemcitabine delivery system available in two drug-loaded strengths: 0.3 g gemcitabine and 0.6 g gemcitabine.
Experimental: Arm 3: BCG-naïve participants with high-risk disease; HS-10566 is placed into the bladder through a urinary placement catheter in participants with BCG-naïve high-risk disease, on Day 1 and will be dosed Q4W for up to the first 24 weeks (6 months), then every 12 weeks through Week 96 (Year 2).	Drug: HS-10566; HS-10566 is an intravesical gemcitabine delivery system available in two drug-loaded strengths: 0.3 g gemcitabine and 0.6 g gemcitabine.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase I: RP2D		Up to 5 months
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.	Up to 36 months
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.	Up to 36 months
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.	Up to 36 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Up to 36 months
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.	up to 2 months
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.	Up to 36 months
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.	Up to 36 months
Phase I: 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.	Up to 36 months
Overall survival (OS)	Overall survival is defined as the duration of time from study entry to death or the date of last contact.	Up to 36 months

Collaborators and Investigators

• Sponsor: Jiangsu Hansoh Pharmaceutical Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Estimated): June 10, 2026
• Primary Completion (Estimated): April 30, 2028
• Study Completion (Estimated): April 30, 2029

Study Registration Dates

• First Submitted: March 8, 2026
• First Submitted That Met QC Criteria: March 8, 2026
• First Posted (Actual): March 13, 2026

Study Record Updates

• Last Update Posted (Actual): March 13, 2026
• Last Update Submitted That Met QC Criteria: March 8, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: High-risk Non-muscle-invasive Bladder Neoplasms Administration, Intravesical
• Other Study ID Numbers: HS-10566-101

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No