Bladder cancer
Conditions
Interventions
Combined therapy group:During the first phase of treatment, the patient receives RC48-ADC and toripalimab. RC48-ADC is administered at a dose of 2.0 mg/kg every 2 weeks (Q2W), and toripalimab is admin
Sponsors
The Third Medical Centre, Chinese PLA General Hospital, Beijing, China
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: 1. Voluntarily agree to participate in the study and sign the informed consent form; 2. Male or female, aged >= 18 years; 3. Life expectancy >= 12 weeks; 4. Patients with histopathologically confirmed intermediate- or high-risk non-muscle invasive bladder urothelial carcinoma who are treatment-naïve but refuse BCG therapy, or who have failed prior BCG therapy or are BCG-intolerant, are eligible for enrollment in this clinical study; 5. Subjects must be able to provide tumor tissue specimens from the primary site for PD-L1 and HER2 testing; HER2 IHC 1+ or 2+ or 3+; 6. ECOG Performance Status score of 0 or 1; 7. Adequate cardiac, bone marrow, hepatic, and renal function (based on the central laboratory's normal reference ranges): (1) Left ventricular ejection fraction (LVEF) >= 50%; (2) Hemoglobin >= 9 g/dL; (3) Absolute neutrophil count (ANC) >= 1.5 × 10^9/L; (4) Platelet count >= 100 × 10^9/L; (5) Serum total bilirubin <= 1.5 × ULN (upper limit of normal) for patients without liver metastases; <= 3 × ULN for patients with liver metastases; (6) ALT and AST <= 2.5 × ULN in the absence of liver metastases; ALT and AST <= 5 × ULN in the presence of liver metastases; (7) Serum creatinine <= 1.5 × ULN; 8. For female subjects: Must be surgically sterile, postmenopausal, or agree to use at least one medically approved form of contraception (e.g., intrauterine device [IUD], oral contraceptives, or condoms) during the study treatment period and for 6 months after the end of study treatment. A serum or urine pregnancy test within 7 days prior to study enrollment must be negative, and the subject must be non-lactating. Male subjects should agree to use at least one medically approved form of contraception (e.g., condoms, abstinence) during the study treatment period and for 6 months after the end of study treatment; 9. Willing and able to comply with the trial and follow-up procedures.
Exclusion criteria
Exclusion criteria: 1. History of malignancies other than urothelial carcinoma, except for the following two cases: (1) The patient has undergone potentially curative therapy and has had no evidence of the disease for 5 years; (2) Successfully resected basal cell carcinoma of the skin, squamous cell carcinoma of the skin, superficial bladder cancer, carcinoma in situ of the cervix, and other carcinoma in situ; 2. Diseases affecting the absorption, distribution, metabolism, or excretion of the investigational drug (e.g., severe vomiting, chronic diarrhea, intestinal obstruction, malabsorption, etc.); 3. Previous history of allogeneic stem cell or solid organ transplantation; 4. Prior systemic anti-tumor therapy (including traditional Chinese medicines with anti-tumor indications) completed less than 4 weeks before the start of study treatment in this study, or adverse events from prior therapy have not recovered to = Grade 1 per CTCAE (except for alopecia and pigmentation); 5. History or current diagnosis of congenital or acquired immunodeficiency diseases; 6. Active or previously documented autoimmune or inflammatory disorders (including but not limited to: autoimmune hepatitis, interstitial pneumonia, inflammatory bowel disease, systemic lupus erythematosus, vasculitis, uveitis, hypophysitis, hyperthyroidism or hypothyroidism, asthma requiring bronchodilator therapy, etc.). Patients with vitiligo or asthma that was fully resolved in childhood and requires no intervention in adulthood may be enrolled; 7. Use of systemic immunosuppressive medications within 2 weeks prior to enrollment, or anticipated need for systemic immunosuppressive therapy during the study period, except for the following: (1) Intranasal, inhaled, topical, or local injection (e.g., intra-articular) corticosteroids; (2) Systemic corticosteroids at doses not exceeding 10 mg/day of prednisone or equivalent; (3) Prophylactic use of corticosteroids for hypersensitivity reactions; 8. Known or suspected history of allergy to disitamab vedotin (RC48), anti-PD-1 class drugs, or history of hypersensitivity to chimeric or humanized antibodies or fusion proteins, or allergy to excipients of the investigational drug(s); 9. History of thrombosis or thromboembolic events within the past 6 months, such as stroke and/or transient ischemic attack, deep vein thrombosis, pulmonary embolism, etc.; 10. Patients assessed by the physician to be at significant risk of bleeding, including but not limited to: significant bleeding (>30 ml within 3 months), hemoptysis (>5 ml within 4 weeks) – if these occur, gastroscopy/assessment can be performed, with endoscopic assessment being definitive; or active bleeding or coagulation disorders, bleeding tendency, or receiving thrombolytic, anticoagulant, or antiplatelet therapy; 11. Cardiovascular disease with significant clinical implications, including but not limited to: acute myocardial infarction within the past 6 months, severe/unstable angina or coronary artery bypass grafting, congestive heart failure (New York Heart Association class >II), poorly controlled arrhythmias or those requiring pacemaker treatment, uncontrolled hypertension (systolic blood pressure =140 mmHg and/or diastolic blood pressure =90 mmHg); 12. Other clinically significant laboratory abnormalities or conditions that, in the investigator's judgment, may affect safety evaluation, such as: uncontrolled diabetes, chronic kidney disease, grade II or higher peripheral neuropathy (CTCAE v5.0), thyroid
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The proportion of patients undergoing radical cystectomy at one year; | — |
Secondary
| Measure | Time frame |
|---|---|
| clinical complete response rate;Progression-free survival;Overall survival;Objective response rate, ORR;Disease Control Rate, DCR;Duration of Response, DoR; | — |
Countries
China
Contacts
Public ContactGu Liangyou
The Third Medical Centre, Chinese PLA General Hospital
Outcome results
None listed