SHR-1501 Combined With SHR-2005 for High-Risk Non-Muscle Invasive Bladder Cancer Which is Not Completely Resectable by TURBt

NCT06588179 | Not Yet Recruiting Phase 1

• 1 other identifier: NMIBC-NCR01
• Study Type: interventional
• Target: 58
• Locations: 1 country
• Sites: 1

Brief Summary

This is a single-center, single-arm, phase Ib/II study, aimed at assessing the safety and efficacy of SHR-1501 in combination with SHR-2005 as treatment for patients with high-risk non-muscle invasive bladder cancer (HR NMIBC) which is not completely resectable by transurethral resection of bladder tumor (TURBt).

Conditions

NMIBC

Outcome Measures

Primary Outcomes (4)

• Phase I : Incidence of dose limiting toxicities (DLTs)

  From Day 1 to Day 21

• Phase I : RP2D（Recommended Phase 2 dose）

  From Day 1 to 90 days after last dose

• Phase I : Incidence and severity of adverse events (AEs)

  From Day 1 to 90 days after last dose

• Phase II : CR rate at 3 months

  Approximately 2 years

Secondary Outcomes (6)

• Phase I : CR rate at 3 months

  From Day 1 to 90 days after last dose

• Phase II : Incidence and severity of adverse events (AEs)

  Approximately 2 years

• Phase Ib/II: PR rate at 3 months

  Approximately 2 years

• Phase Ib/II: CR rate at 6 months and 12months

  Approximately 2 years

• Phase Ib/II: Duration of CR (DoR)

  Approximately 2 years

Study Arms (1)

Arm：SHR-1501+SHR-2005

EXPERIMENTAL

Drug: SHR-1501+SHR-2005

Interventions

SHR-1501+SHR-2005 DRUG

SHR-1501, instillation；SHR-2005, instillation

Arm：SHR-1501+SHR-2005

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥18 years old, both genders
• Previous pathological biopsy was diagnosed as high-risk NMIBC
• Tumors cannot be completely resected by TURBT（at least 2 senior urologists assessed that the lesion area is too extensive to be completely resected）
• Ineligible or unwilling to undergo radical cystectomy
• TURBT was performed within 6 weeks
• Agreed to provide cystoscopic biopsy specimens for review
• ECOG performance status of 0-2
• Life expectancy ≥ 2 years
• Adequate organ function：
• Hematological indexes: ANC ≥1.5x10\^9/L, PLT ≥100x10\^9/L, Hb ≥ 90 g/L;
• Liver function: TBIL ≤1.5 ULN; ALT and AST≤2.5 ULN; Albumin \> 3g/dL
• Renal function: Cr≤1.5 ULN or creatinine clearance ≥ 60 ml/min (Cockcroft-Gault formula); if proteinuria ≥++, requiring 24-hour urine protein level ≤1.0g;
• ECG: females QTcF ≤470ms and males ≤450ms
• Cardiac ultrasound: LVEF≥50%
• Coagulation: INR or PT ≤1.5 ULN，APTT≤1.5 ULN

You may not qualify if:

• Previous pathological biopsy was diagnosed with muscle-invasive bladder cancer at T2 or higher stages
• Received any other intravesical chemotherapy treatment within 2 weeks or received any other clinical drugs within 4 weeks
• History of allergy to any of the study drugs or study drug components
• Upper urinary tract tumor detected by CTU or MRU during screening period or other concomitant malignant tumors within 5 years before the first administration
• Previously received any TNFR agonist antibody therapy(such as OX40, CD27, CD357 antibodies), IL-15 agonist antibody therapy, or IL-2 agonist antibody therapy
• Oversize surgery or severe trauma within 4 weeks before the first use of research drugs
• Previously discontinued bladder instillation therapy due to adverse reactions such as sepsis, systemic infection, or urinary incontinence
• Active/uncontrolled impairment of the urogenital system, kidneys, liver, gallbladder, cardiovascular system, gastrointestinal tract, nervous system, or hematopoietic system, which may lead to complications for the subject when receiving intravesical therapy and/or general anesthesia
• A history of interstitial lung disease or non-infectious pneumonitis requiring treatment with glucocorticoids, or current presence of interstitial pneumonitis or non-infectious pneumonitis, or a history of other severe pulmonary diseases
• A history of immunodeficiency, including HIV seropositivity, other acquired or congenital immunodeficiency diseases, a history of organ transplantation, or current use of immunosuppressants
• History of clinically significant cardiovascular disease within 6 months before the first administration
• Investigator-assessed concern for medication safety; severe infections requiring antibiotic, antiviral or antifungal drug control; and unexplained fever \> 38.5°C within 2 weeks
• Patient with active hepatitis B (HBeAg positive and HBV DNA≥500 IU/mL), hepatitis C (HCV antibody positive and HCV RNA higher than the detection limit of the analytical method)
• Adverse reactions of previous anti-tumor treatment have not recovered to Grade≤1 per NCI-CTCAE v5.0
• The presence of any other conditions that the investigator deems inappropriate to participate in this study, including serious physical or mental illness, abnormal laboratory tests, and other factors that may increase the risk of participating in the study, or interfere with the results of the study

Sponsors & Collaborators

• Fudan University: lead

Study Sites (1)

Fudan University Shanghai Cancer Center

Shanghai, Shanghai Municipality, 200032, China

Location

MeSH Terms

Conditions

Non-Muscle Invasive Bladder Neoplasms

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Urinary Bladder Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases

Study Officials

• Dingwei Ye, MD

  Fudan University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Dingwei Ye, MD

CONTACT

86-21-64175590; dwyeli@163.com

Xiaolin Lu, MD

CONTACT

86-21-64175590

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief Physician

Study Record Dates

• First Submitted: September 5, 2024
• First Posted: September 19, 2024
• Study Start: October 1, 2024
• Primary Completion (Estimated): October 1, 2027
• Study Completion (Estimated): October 1, 2027
• Last Updated: September 19, 2024

Record last verified: 2024-09

Locations

CN (1)