RC48-ADC in Adjuvant/Salvage Treatment of HER2 Positive Non-muscle-invasive Bladder Cancer

A Multicenter Phase II Study of RC48-ADC in Adjuvant/Salvage Treatment of HER2 Positive High-risk Non-muscle-invasive Bladder Cancer

This study will evaluate the efficacy and safety of intravenous RC48-ADC in adjuvant/salvage treatment of HER2 positive high-risk non-muscle-invasive bladder cancer.

Study Overview

• Status: Not yet recruiting
• Conditions: Non-muscle Invasive Bladder Cancer
• Intervention / Treatment: Drug: RC48-ADC

Detailed Description

This study is a multicenter phase II study, which aims to evaluate the efficacy and safety of intravenous RC48-ADC in adjuvant/salvage treatment of HER2 positive high-risk non-muscle-invasive bladder cancer.

• Study Type: Interventional
• Enrollment (Estimated): 77
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Hao Zeng; Phone Number: 8602885422114; Email: kucaizeng@163.com
• Study Contact Backup: Name: Junru Chen; Phone Number: 8602885422114; Email: jrchen@scu.edu.cn

Study Locations

• China
  • Sichuan
    • Chengdu, Sichuan, China, 610041
      • West China Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Be willing and able to provide written informed consent/assent for the trial.
• Life expectancy ≥12 weeks.
• Have a histologically-confirmed diagnosis of high-risk non-muscle-invasive (according to 2023 NCCN guidelines for bladder cancer) transitional cell carcinoma of the bladder. Subjects with tumors of mixed transitional/non-transitional cell histology are allowed, but transitional cell carcinoma must be the predominant histology.
• Have been treated with adequate BCG therapy and failed (according to 2023 EAU guidelines for NMIBC, for salvage treatment arm).
• Have elected not to undergo, or are considered ineligible for radical cystectomy, as determined by the treating surgeon.
• Have tumor tissues for HER2 IHC evaluation and have a HER2 expression score of HER2 2+ or HER2 3+ reviewed by an independent pathologist at the central laboratory.
• Have a performance status of 0, 1 or 2 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale.
• Demonstrate adequate organ function.
• Female subjects of childbearing potential must have a negative urine or serum pregnancy test within 7 days prior to receiving the first dose of study medication.
• Male subjects of childbearing potential (Section 5.7.2) must agree to use an adequate method of contraception starting with the first dose of study therapy through 6 months after the last dose of study therapy.

Exclusion Criteria:

• Has muscle-invasive (i.e. T2, T3, T4) locally advanced non-resectable or metastatic urothelial carcinoma.
• Has concurrent extra-vesical (i.e. urethra, ureter or renal pelvis) non-muscle invasive transitional cell carcinoma of the urothelium.
• Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment.
• Has undergone any intervening intravesical chemotherapy or immunotherapy from the time of most recent cystoscopy/TURBT to starting trial treatment. (Note: A single dose of intravesical treatment given as part of the most recent cystoscopy/TURBT, during the screening period, such as with chemotherapy as per local / regional practices, is acceptable.).
• Allergic to study therapy.
• Has a known additional malignancy that has had progression or has required active treatment in the last five years.
• Has an active autoimmune disease that has required systemic treatment in past 2 years.
• Have diseases that may interfere with the study treatment or severe and uncontrolled concomitant diseases.
• Has had an allogeneic tissue/solid organ transplant.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Adjuvant RC48-ADC; In this arm, RC48-ADC is evaluated in patients with HER2-positive high-risk non-muscle-invasive bladder cancer as an adjuvant treatment.	Drug: RC48-ADC; Patients are treated with RC48-ADC at 2.0 mg/kg as an intravenous infusion over 30-90 minutes (60 minutes is recommended) once every 2 weeks for 12 weeks.
Experimental: Salvage RC48-ADC; In this arm, RC48-ADC is evaluated in patients with HER2-positive non-muscle-invasive bladder cancer who failed BCG treatment as an adjuvant treatment.	Drug: RC48-ADC; Patients are treated with RC48-ADC at 2.0 mg/kg as an intravenous infusion over 30-90 minutes (60 minutes is recommended) once every 2 weeks for 12 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
12-month recurence-free survival rate	The probability of patients remaining free of high-risk NMIBC or worse for at least 12 months after first dose of RC48-ADC adjuvant treatment	From treatment initiation to 12 month
3-month pathological complete response rate	The proportion of patients are negative for urine cytology and cystoscopy at 3 month after first dose of RC48-ADC salvage treatment	From treatment initiation to 3 month
Adverse events	The type, incidence, relatedness, and severity of adverse events	From patient screening to 30 days after end of cycle 6

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
6-month recurence-free survival rate	The probability of patients remaining free of high-risk NMIBC or worse for at least 6 months after first dose of RC48-ADC adjuvant treatment	From treatment initiation to 6 month
Duration of response	Time from complete response to recurrence of any disease	From time of complete response to up to 60 months
Recurrence-free survival	Time from first dose of RC48-ADC adjuvant treatment to high-risk NMIBC recurrence or worse	From time of first dose of RC48-ADC adjuvant treatment to up to 60 months
Progression-free survival	Time from first dose of RC48-ADC treatment to progression to higher stage or death	From time of first dose of RC48-ADC treatment to up to 60 months
Overall survival	Time from first dose of RC48-ADC treatment to death from any cause	From time of first dose of RC48-ADC treatment to up to 60 months
Quality of life assessed by EQ-5D scale	Assessed by eEuroQoL EQ-5D scale, higher scores mean better outcomes	After every cycle of treatment and 30 days after end of cycle 6

Collaborators and Investigators

• Sponsor: West China Hospital
• Collaborators: RemeGen Co., Ltd.
• Investigators: Principal Investigator: Hao Zeng, West China Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): August 1, 2023
• Primary Completion (Estimated): August 1, 2025
• Study Completion (Estimated): August 1, 2026

Study Registration Dates

• First Submitted: August 3, 2023
• First Submitted That Met QC Criteria: August 10, 2023
• First Posted (Actual): August 18, 2023

Study Record Updates

• Last Update Posted (Actual): August 18, 2023
• Last Update Submitted That Met QC Criteria: August 10, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Urologic Diseases; Carcinoma; Neoplasms, Glandular and Epithelial; Urinary Bladder Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Urinary Bladder Neoplasms; Non-Muscle Invasive Bladder Neoplasms
• Other Study ID Numbers: 2023(24)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No