RC48 Combined With Toripalimab and Radiotherapy for Bladder Sparing Treatment in MIBC

NCT05979740 | Unknown Phase 2 DMC

• 1 other identifier: LY2023-002-A
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

This is a prospective, open, single-center clinical study of RC48 combined with PD-1 and radiotherapy as bladder-preserving therapy in patients with muscular invasive bladder uroepithelial carcinoma with high HER-2 expression (IHC 2+ or 3+). The study was conducted in accordance with the Good Practice for Clinical Trials of Pharmaceutical Products (GCP). Six patients were enrolled in this study. Each patient received RC48 injection \[2.0 mg/kg, Q2W, iv\] and Toripalimab injection \[3mg/kg, Q2W, iv\] for 1\~2 cycles, and radiotherapy at the second or third cycle. The total dose of bladder irradiation field was greater than 50Gy (about 30 times), and the safety monitoring of the subjects was conducted within 28 days after receiving the study drug treatment for the first time. Adverse events were graded using the National Cancer Institute (NCI) Standard for the Assessment of Common Terminology for Adverse Events (CTCAE) Version 5.0 guidelines, and the occurrence of DLT in patients was observed. If the subject does not complete the safety assessment for the tolerance observation period for non-dose tolerance reasons, a new subject will be replaced.

Conditions

Muscle Invasive Bladder Cancer; HER2 Expression; Radiotherapy; PD-1; Antibody-drug Conjugates

Keywords

Muscle Invasive Bladder Cancer; HER2 expression; Radiotherapy; PD-1; ADC; Bladder Sparing

Outcome Measures

Primary Outcomes (1)

• Safety

  Adverse events will be defined according to NCI CTCAE, Version 5.0

  Up to 28 days

Secondary Outcomes (7)

• Percent of Patients With Complete Response (CR)

  Up to 3 months

• Percent of Patients With Complete Response (CR)

  Up to 12 months

• Percent of Patients With Complete Response (CR)

  Up to 24 months

• 1-yr and 2-yr Bladder-intact Event-free Survival (BI-EFS)

  Up to 24 months

• Recurrence Free Survival (RFS)

  Up to 24 months

Study Arms (1)

RC48+Toripalimab+Radiotherapy

EXPERIMENTAL

RC48: 2.0 mg/kg, Q2W, iv; Toripalimab: 3mg/kg, Q2W, iv; Radiotherapy: total dose was greater than 50Gy (about 30 times).

Drug: Disitamab Vedotin and Toripalimab

Interventions

Disitamab Vedotin and Toripalimab DRUG

Each patient received RC48 injection \[2.0 mg/kg, Q2W, iv\] and Toripalimab injection \[3mg/kg, Q2W, iv\] for 1\~2 cycles, and Radiotherapy radiotherapy at the second or third cycle. The total dose of bladder irradiation field was greater than 50Gy (about 30 times), and the safety monitoring of the subjects was conducted within 28 days after receiving the study drug treatment for the first time.

Also known as: RC48, JS001

RC48+Toripalimab+Radiotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• 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
• 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);
• 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.

Sponsors & Collaborators

• RenJi Hospital: lead

Study Sites (1)

Renji Hospital, School of Medicine, Shanghai Jiao Tong University

Shanghai, Shanghai Municipality, 200127, China

RECRUITING

Related Publications (1)

• Zhang L, Jin D, Zang J, Qian L, Zhang T, Wu Y, Ding Y, Xie F, Tang H, Xia J, Cao D, Zhang R, Zhuang G, Chen H. Disitamab vedotin combined with toripalimab and radiotherapy for multimodal organ-sparing treatment of muscle invasive bladder cancer: a proof-of-concept study. Neoplasia. 2025 Oct;68:101216. doi: 10.1016/j.neo.2025.101216. Epub 2025 Aug 6.

  PMID: 40774226 DERIVED

MeSH Terms

Interventions

disitamab vedotin; toripalimab; RC48 antibody

Study Officials

• Haige Chen

  RenJi Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Haige Chen

CONTACT

02168383575; kirbyhaige@aliyun.com

Ruiyun Zhang

CONTACT

02168383575

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 31, 2023
• First Posted: August 7, 2023
• Study Start: August 1, 2023
• Primary Completion: December 13, 2023
• Study Completion: February 13, 2024
• Last Updated: August 31, 2023

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)