Clinical trial NCT06588179: SHR-1501 Combined With SHR-2005 for High-Risk Non-Muscle Invasive Bladder Cancer Which is Not Completely Resectable by TURBt
Official title: Phase Ib/II Clinical Study of SHR-1501 Combined With SHR-2005 in the Treatment of Patients With High-Risk Non-Muscle Invasive Bladder Cancer Which is Not Completely Resectable by TURBt
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE1
PHASE2
Conditions: NMIBC
Lead sponsor: Fudan University
Sponsor class: OTHER
First posted: 2024-09-19
Enrollment: 58
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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).


Eligibility criteria: Inclusion Criteria:

1. Age ≥18 years old, both genders
2. Previous pathological biopsy was diagnosed as high-risk NMIBC
3. Tumors cannot be completely resected by TURBT（at least 2 senior urologists assessed that the lesion area is too extensive to be completely resected）
4. Ineligible or unwilling to undergo radical cystectomy
5. TURBT was performed within 6 weeks
6. Agreed to provide cystoscopic biopsy specimens for review
7. ECOG performance status of 0-2
8. Life expectancy ≥ 2 years
9. Adequate organ function：

   1. Hematological indexes: ANC ≥1.5x10\^9/L, PLT ≥100x10\^9/L, Hb ≥ 90 g/L;
   2. Liver function: TBIL ≤1.5 ULN; ALT and AST≤2.5 ULN; Albumin \> 3g/dL
   3. 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;
   4. ECG: females QTcF ≤470ms and males ≤450ms
   5. Cardiac ultrasound: LVEF≥50%
   6. Coagulation: INR or PT ≤1.5 ULN，APTT≤1.5 ULN
10. Female or male subjects of childbearing age who have not undergo surgical sterilization shall agree to use contraceptive measures (such as intrauterine device and contraceptive pill) during the study treatment period and within 3 months after the end of the study treatment period, and both female subjects and female partners of male subjects should use highly effective contraceptive methods; the Female subjects of childbearing age who have not undergone surgical sterilization must have a negative serum HCG test result within 7 days prior to the first administration and must be non-lactating.
11. Volunteered to join the study, signed the informed consent, and had good compliance with follow-up

Exclusion Criteria:

1. Previous pathological biopsy was diagnosed with muscle-invasive bladder cancer at T2 or higher stages
2. Received any other intravesical chemotherapy treatment within 2 weeks or received any other clinical drugs within 4 weeks
3. History of allergy to any of the study drugs or study drug components
4. Upper urinary tract tumor detected by CTU or MRU during screening period or other concomitant malignant tumors within 5 years before the first administration
5. Previously received any TNFR agonist antibody therapy(such as OX40, CD27, CD357 antibodies), IL-15 agonist antibody therapy, or IL-2 agonist antibody therapy
6. Oversize surgery or severe trauma within 4 weeks before the first use of research drugs
7. Previously discontinued bladder instillation therapy due to adverse reactions such as sepsis, systemic infection, or urinary incontinence
8. 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
9. 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
10. A history of immunodeficiency, including HIV seropositivity, other acquired or congenital immunodeficiency diseases, a history of organ transplantation, or current use of immunosuppressants
11. History of clinically significant cardiovascular disease within 6 months before the first administration
12. Investigator-assessed concern for medication safety; severe infections requiring antibiotic, antiviral or antifungal drug control; and unexplained fever \> 38.5°C within 2 weeks
13. 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)
14. Adverse reactions of previous anti-tumor treatment have not recovered to Grade≤1 per NCI-CTCAE v5.0
15. 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

Primary outcomes:
measure: Phase I : Incidence of dose limiting toxicities (DLTs)
timeFrame: From Day 1 to Day 21
measure: Phase I : RP2D（Recommended Phase 2 dose）
timeFrame: From Day 1 to 90 days after last dose
measure: Phase I : Incidence and severity of adverse events (AEs)
timeFrame: From Day 1 to 90 days after last dose
measure: Phase II : CR rate at 3 months
timeFrame: Approximately 2 years
Secondary outcomes:
measure: Phase I : CR rate at 3 months
timeFrame: From Day 1 to 90 days after last dose
measure: Phase II : Incidence and severity of adverse events (AEs)
timeFrame: Approximately 2 years
measure: Phase Ib/II: PR rate at 3 months
timeFrame: Approximately 2 years
measure: Phase Ib/II: CR rate at 6 months and 12months
timeFrame: Approximately 2 years
measure: Phase Ib/II: Duration of CR (DoR)
timeFrame: Approximately 2 years
measure: Phase Ib/II: Cystectomy-Free Survival (CFS)
timeFrame: Approximately 2 years
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Fudan University Shanghai Cancer Center
state: Shanghai
Study officials:
affiliation: Fudan University
name: Dingwei Ye, MD
role: PRINCIPAL_INVESTIGATOR
References: