A Clinical Study of RC48-ADC Combined With Triplizumab For Treatment of Myometrial Invasive Bladder Cancer

• Status: Not yet recruiting
• Trial end date: 2024-10-01
• Target enrollment: 0
• Participant gender: All

Summary

The purpose of this project is to explore whether Monoclonal Antibody-MMAE Conjugate for Injection (RC48-ADC) combined with Triplizumab as a preoperative neoadjuvant therapy for myometrial invasive bladder cancer (MIBC) can achieve a good tumor descending period, so as to prolong disease-free survival and overall survival.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School

Criteria

Inclusion Criteria:

1. Patients with myometrial invasive bladder cancer are prepared for radical cystectomy;

2. HER2 overexpression confirmed by pathological biopsy: IHC2+ or IHC3+; subjects can provide tumor samples detected by HER2;

3. Age ≥ 18 years old and ≤ 80 years old;

4. Tumor clinical stage is (c) T2-3bN0M0;

5. ECOG score ≤ 1;

6. Subjects have not received systemic chemotherapy, ADC drugs or immunotherapy.

7. The important laboratory examination indexes meet the following requirements:

1. Hemoglobin ≥ 90g/L.

2. Absolute neutrophil count (ANC) ≥ 1.5 × 109 / L.

3. Platelet ≥ 100 × 109 / L.

4. 3.5mmol/L ≤ serum potassium ≤ 5.5mmol/L.

5. Liver function index: ALT, AST ≤ 1.5 times the upper limit of normal value (ULN), TBIL ≤ 1.5ULN.

6. eGFR ≥ 50 mL/min

7. The left ventricular ejection fraction (LVEF) was 50%.

8. Subjects with serum creatinine ≤ 1.5 × ULN or creatinine clearance rate (CrCl) ≥ 50mL/min

8. The subject is volunteer to participate, and the subject must signed an informed consent form (ICF), indicating that it understands the purpose of this study and the required procedures, and is willing to participate in the study. Subjects must be willing and abide by prohibition and restrictions specified in the research program

9. Female subjects should be surgically sterilized or postmenopausal, or agree to use at least one medically approved contraceptive method (such as intrauterine device, contraceptive or condom) during the study treatment and within 6 months after the end of the study treatment period. The blood pregnancy test must be negative within 7 days before the study, and it must be non-lactation. Male subjects should agree to use at least one medically approved contraceptive method (such as condoms, abstinence, etc.) during the study treatment period and within 6 months after the end of the study treatment period.

10. Subjects are willing and able to follow the trial and follow-up procedures

Exclusion Criteria:

1. Patients who cannot tolerate radical cystectomy;

2. patients with myometrial invasive urothelial carcinoma with distant metastasis (abdominal CT scan + enhancement, chest CT scan, ECT- bone scan, PET-CT, MRI, etc.).

3. Uncontrollable concomitant diseases, including, but not limited to, persistent infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, arrhythmia, interstitial lung disease, severe chronic gastrointestinal disease associated with diarrhoea, or mental illness / social conditions, which will limit compliance with research requirements, significantly increase the risk of AE or impair the patient's ability to write informed consent.

4. Patients with drug allergy or hypersensitivity, patients with autoimmune diseases;

5. Received antineoplastic therapy within 3 weeks before the start of the study, including chemotherapy, radiotherapy, targeted therapy, immunotherapy and clinical research antineoplastic drug therapy.

6. Had received live attenuated vaccine or had serious infection or planned to receive any vaccine during the study period one month before entering the group.

7. Systemic corticosteroids or other systemic immunosuppressive drugs are used within 2 weeks before enrollment, or systemic immunosuppressive drugs are expected to be needed during the trial;

8. Serovirological examination (based on the normal value of the research center):

HBsAg or HBcAb test results are positive, while HBVDNA copies are positive; HCVAb test results are positive (only if the PCR test result of HCVRNA is negative).

The results of HIVAb test were positive.

9. Heart failure classified as grade 3 or above by the New York College of Cardiology (NYHA);

10. Active or progressive infections that require systematic treatment, such as active pulmonary tuberculosis;

11. Systemic diseases that have not been stably controlled by researchers, including diabetes, hypertension, liver cirrhosis, interstitial pneumonia, obstructive pulmonary disease, etc.

12. Serious arteriovenous thrombosis or cardio-cerebrovascular accidents occurred within 1 year before administration, such as deep venous thrombosis, pulmonary embolism, cerebral infarction, cerebral hemorrhage, myocardial infarction, etc., except for lacunar infarction that is asymptomatic and does not require clinical intervention;

13. Previous allogeneic hematopoietic stem cell transplantation;

14. Previous antibody-coupled drug therapy;

15. Pregnant or lactating women.

16. Suffering from any other disease, abnormal metabolism, abnormal physical examination or abnormal laboratory examination, according to the researchers, there is reason to suspect that the patient has a disease or condition that is not suitable for the use of research drugs, or will affect the interpretation of the results of the study, or put the patient at high risk;

17. Other situations that some researchers believe are not appropriate to participate in this study.

Elimination standard

1. Received other local or systemic treatments at the same time;

2. The simultaneous use of other foods and drugs that affected the judgment of tolerance; (3) In violation of the requirements of the study scheme, drugs were not given according to the dose and course of treatment specified in the study scheme;

(4) The quality of data recording was poor and the data was incomplete and inaccurate.

Termination criteria

1. Subjects asked to stop using the research therapy.

2. Recurrence (local, regional or distant).

3. For any clinical AE, laboratory examination abnormalities or concomitant diseases, according to the judgment of the researchers, continuing to participate in the study is not the greatest benefit to the subjects.

4. The researcher terminated the study.

5. The informed consent form can no longer be freely signed because of crime or forcible detention for the treatment of mental illness or physical illness (such as infectious diseases).

6. The adverse events and severity of other clinical trials of this study or study drugs suggest that the risk of the subjects is too high to continue the study;

7. The speed of enrollment in the research center is too slow to complete the enrollment plan within a limited time;

8. The quality of the clinical data is not good enough to continue the follow-up study;

9. The study is terminated due to the regulatory requirements or policy changes of the national drug administration.