Bladder-preserving treatment for muscle invasive bladder cancer using RC48 and Toripalimab

RC48 Combined With PD-1 and Radiotherapy as Bladdersparing Therapy in Patients With Muscular Infiltrating Bladder Uroepithelial Carcinoma With Limited HER-2 Expression Following Maximum Electrical Resection or Partial Cystectomy

This study is testing a new treatment that combines two medications and radiation to see if it can help people with muscle invasive bladder cancer keep their bladders while effectively fighting the disease.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 6 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: RenJi Hospital (Academic / other)
• Drugs / interventions: immunotherapy, Toripalimab, radiation
• Locations: 1 site (Shanghai, Shanghai)
• Trial ID: NCT05979740 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates the effectiveness of RC48 combined with the PD-1 inhibitor Toripalimab and radiotherapy as a bladder-sparing treatment for patients with muscle invasive bladder cancer that exhibits high HER-2 expression. The study involves administering RC48 and Toripalimab every two weeks for up to 12 cycles, alongside radiotherapy delivering over 50Gy to the bladder. Patients undergo initial surgical procedures and are closely monitored for adverse events and treatment efficacy through imaging and pathology evaluations. The goal is to assess the safety and effectiveness of this combined approach in preserving bladder function while treating cancer.

Who should consider this trial

Good fit: Ideal candidates are patients with muscle invasive bladder cancer who have high HER-2 expression and are scheduled for bladder-preserving therapy.

Not a fit: Patients with low HER-2 expression or those who cannot tolerate radiotherapy may not benefit from this treatment.

Why it matters

Potential benefit: If successful, this treatment could offer a new option for patients with muscle invasive bladder cancer, potentially preserving bladder function while effectively managing the disease.

How similar studies have performed: While there have been studies exploring similar combinations of therapies, this specific approach targeting high HER-2 expression in muscle invasive bladder cancer is relatively novel.

Eligibility criteria

Inclusion criteria:

ECOG PS: 0～1；Subjects underwent TURBT surgery or partial cystectomy and imaging diagnosis, which was determined to be muscular infiltrating urothelial carcinoma of the bladder (urothelial carcinoma being the main pathological component: 50%) and planned to undergo radical total cystectomy + lymph node dissection + urine flow diversion; cT2-T4a N0 M0 (CT/MRI ± PET/CT)；Undergo TURBT or partial cystectomy；Tissue examination specimens with TURBT or partial cystectomy；Expected survival ≥3 months；Immunohistochemical staining of tissue after final TURBT or partial cystectomy showed IHC 2+ or 3+；The major organs are functioning normally, the following criteria are met:

1. The blood routine examination criteria should meet (no blood transfusion and no treatment with granulocyte colony stimulating factor within 14 days before enrollment) :

   i. Absolute count of neutrophils (ANC) ≥1,000/mm3 ii. Platelet count ≥75,000/mm3 iii. Hemoglobin ≥ 8.0g /dL
2. Liver function:

   i. Total bilirubin ≤1.5× prescribed ULN or direct bilirubin ≤ULN for subjects with total bilirubin levels \>1.5×ULN ii. Upper limit of normal values (ULN) ≤2.5 times of alanine Aminotransferase (ALT) and aspartate Aminotransferase (AST) Note: ≤1.5× ULN (This criterion only applies to patients who have not received anticoagulant therapy; Patients receiving anticoagulant therapy should keep anticoagulants within therapeutic limits);
3. Kidney function:

The Cockcroft-Gault formula was used to determine the creatinine clearance (CrCl) \> 30 mL/min.

Subjects (or their legal representatives) must sign an informed consent form (ICF) indicating that they understand the purpose and procedures of the study and are willing to participate in the study; Fertile women must have a negative pregnancy test result (beta-hCG) (urine or serum) within 7 days before the study drug is first administered.

Exclusion criteria: Previously received anti-PD-1, anti-PD-L1, anti-PD-L2 therapy, including adjuvant therapy stage；Known allergy to recombinant humanized anti-PD-1 monoclonal antibody drugs and their components；Those who had received other antitumor therapy (including corticosteroid therapy, immunotherapy) or participated in other clinical studies within 4 weeks prior to study therapy, or had not recovered from previous toxicity (except for 2 degree hair loss and 1 degree neurotoxicity)；Pregnant or lactating woman；HIV positive；People with active hepatitis B or C；A history of definite active tuberculosis；Have active autoimmune diseases requiring systemic treatment within the past 2 years (e.g., use of disease-regulating drugs, corticosteroids, or immunosuppressive drugs) that allow for relevant replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for renal or pituitary insufficiency)；Other serious, uncontrolled concomitant diseases that may affect protocol adherence or interfere with interpretation of results, These include active opportunistic or progressive (severe) infections, uncontrolled diabetes, cardiovascular disease (heart failure of Grade Ⅲ or Ⅳ as defined by the New York Heart Association scale, heart block of degree Ⅱ or higher, myocardial infarction within the past 6 months, unstable arrhythmia or unstable angina, cerebral infarction within 3 months, etc.), or pulmonary disease (interstitial pneumonia, History of obstructive pulmonary disease and symptomatic bronchospasm)；Those who received the live vaccine within 4 weeks before treatment began；Previously received allogeneic hematopoietic stem cell transplantation or solid organ transplantation；Major surgical procedures (excluding diagnostic surgery) within 4 weeks prior to the start of treatment；Those who have a history of psychotropic substance abuse and cannot abstain or have a history of mental disorders；A large amount of pleural fluid or ascites with clinical symptoms or symptomatic management；Have had other unhealed malignancies in the past 5 years, excluding those that are apparently cured or curable, such as basal or squamous cell skin cancer, localized low-risk prostate cancer, carcinoma in situ of the cervix or carcinoma in situ of the breast; Remarks: Patients with localized low-risk prostate cancer (defined as stage ≤T2b, Gleason score ≤7, and PSA≤20ng/mL at the time of prostate cancer diagnosis (as measured) who had received radical therapy and had no biochemical recurrence of prostate specific antigen (PSA) were eligible to participate in this study)；Urothelial carcinoma associated with upper urinary tract (renal pelvis and ureteral urothelial carcinoma)；Other severe, acute, or chronic medical or psychiatric conditions or laboratory abnormalities that, according to the investigator, may increase the risks associated with study participation or may interfere with the interpretation of the study results

Where this trial is running

Shanghai, Shanghai

• Renji Hospital, School of Medicine, Shanghai Jiao Tong University — Shanghai, Shanghai, China (Recruiting)

Study contacts

• Principal investigator: Haige Chen — RenJi Hospital
• Study coordinator: Haige Chen

Conditions Muscle Invasive Bladder Cancer; HER2 Expression; Radiotherapy; PD-1; Antibody-drug Conjugates; HER2 expression; ADC; Bladder Sparing