High-risk non-muscle-invasive bladder cancer
Conditions
Interventions
Experimental group:Dose Exploration Phase:
The aim is to evaluate the safety and tolerability of ADC drugs and to clarify the RP2D. SHR-A2102 is administered by transvesical perfusion, and the dosing
Sponsors
Shanghai General Hospital
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: 1. Volunteer to participate in this clinical study, understand the study procedures, and be able to sign the informed consent form in writing; 2. Age>=18 years old, gender is not limited; 3. Eastern Cooperative Oncology Group (ECOG) performance status score =2 years; 5. Able to provide sufficient fresh or archival tumor tissue specimens for the detection of Nectin-4 expression levels; 6. Previous pathological biopsy diagnosed as high-risk NMIBC (see Annex 1 for the definition of "high-risk"); 7. Underwent cystoscopy within 6 weeks before the first dose without resectable lesions (Ta/T1 resectable lesions can be removed during cystoscopy during the screening period), or residual lesions were only CIS; For T1 subjects, if no muscularis propria is found in the resected tissue after the last transurethral bladder tumor resection (TURBT), TURBT must be performed again and the pathological examination confirms that the muscularis propria tissue is included; 8. Unsuitable or unwilling to undergo radical cystectomy; 9. No response to previous BCG therapy or inability to tolerate BCG treatment assessed by the investigator and relapse before enrollment after chemotherapy perfusion (gemcitabine, epirubicin, pirubicin, mitomycin); Non-response to BCG therapy is defined as meeting any of the following conditions: (1) persistent/recurrent CIS or combined Ta/T1 within 12 months of adequate treatment with BCG; (2) Relapse of high-grade Ta/T1 within 6 months of adequate treatment with BCG; (3) High-grade T1 was assessed for the first time after BCG induction was completed. Adequate treatment with BCG as described above: Completion of 5 of 6 first induction perfusions and 2 of 3 maintenance perfusions or completion of 5 of 6 first induction perfusions and 2 of 6 reinduction perfusions, if BCG is used irregularly, the total number of uses must be >=6. ); 10. Vital organ function meets the following criteria: - Blood routine test (no blood transfusion and blood products within 14 days before blood routine examination, not corrected with G-CSF or other hematopoietic stimulating factors): absolute neutrophil count (ANC) >=1.0×10^9/L; Platelet count (PLT)>=100×10^9/L; Hemoglobin (Hb)>=80g/L; - Liver function tests: total bilirubin (TBIL) =50%; - Coagulation function test: APTT<=1.5×ULN, while INR or PT<=1.5×ULN; 11. Use contraceptive measures for contraception during the study treatment period and within 6 months after the end of the study treatment period, female subjects of childbearing potential or male subjects whose partners are women of childbearing potential need to use highly effective contraceptive methods; Female subjects of childbearing potential must have a negative serum HCG test within 7 days prior to the first dose and must be non-lactating.
Exclusion criteria
Exclusion criteria: 1. Previous antibody conjugate therapy with the following characteristics: Nectin-4 (if enrolled in SHR-A2102 treatment), such as 9MW2821, etc.; The ingredients contain topoisomerase I inhibitors, such as EnHertu (DS-8201a), U3-1402, etc. 2. Those who have received the following treatments in the past and have not had disease progression before enrollment as judged by the investigator: - Cytotoxic chemotherapy drugs or other drugs (such as oncolytic virus, IL-2) treated by vesical perfusion; - immune checkpoint inhibitor therapy; - Other investigational drugs for the treatment of NMIBC. 3. Is receiving study treatment in other clinical trials or is less than 4 weeks from the end of the first dose of this study; 4. Previous or current upper urinary tract tumors or urethral prostate tumors, or other malignant tumors within 5 years of the first dose (except for carcinoma in situ that has completely resolved and malignant tumors that are judged to be slow progression by the investigator); 5. Severe infection (such as requiring intravenous antibiotics, antifungals or antiviral drugs > 7 days) within 4 weeks before the first dose, or unexplained fever >38.5°C during the screening period/before the first dose; Past medical history or examination suggests active tuberculosis within 1 year before the first dose; 6. Patients with clear urinary tract infection or gross hematuria, and the investigator assesses that it affects the safety of medication; 7. History of significant clinically significant cardiovascular disease, including but not limited to: (1) congestive heart failure (NYHA grade >=2); (2) Unstable angina; (3) Myocardial infarction in the past 6 months; (4) Any supraventricular arrhythmia or ventricular arrhythmia requiring treatment or intervention; 8. History of immunodeficiency, including positive HIV serology, other acquired or congenital immunodeficiency diseases, history of organ transplantation, or use of immunosuppressive drugs; 9. Those with active hepatitis B (HBeAg positive and HBV DNA>=500 IU/mL), hepatitis C (hepatitis C antibody positive and HCV RNA higher than the lower limit of detection of the analytical method); 10. Known allergy or intolerance to the study drug or excipients; Other serious physical or psychiatric illnesses, laboratory test abnormalities, and other factors that may increase the risk of participation in the study or interfere with the results of the study; and any other condition that the investigator deems unsuitable for participation in this study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Any study drug-related event occurring in a DLT (i.e., the first dose of medication during the induction period to the target dose level): hematologic toxicity; hepatotoxicity; Urinary tract-related adverse reactions; Non-hematologic toxicity of >=Grade 3;;DFS rate at 12 months;Maximum tolerated dose;Recommended dose for phase II clinical trial; | — |
Secondary
| Measure | Time frame |
|---|---|
| Type, incidence, severity (rated according to CTCAE v5.0), duration, and correlation with study drug of AEs and SAEs;Relationship between expression status of Nectin-4 in tumor tissue and efficacy;Efficacy endpoint; | — |
Countries
China
Contacts
Public ContactHan Bangmin
Shanghai General Hospital
Outcome results
None listed