A Study of RC48-ADC Combined With Toripalimab For First-line Treatment of Urothelial Carcinoma

A Open-Label, Multicenter, Randomised, Controlled Phase 3 Study of RC48-ADC Plus Toripalimab Versus Chemotherapy Alone in Previously Untreated Unresectable Locally Advanced or Metastatic Urothelial Carcinoma With HER2-Expressing

This is a Phase 3, Open-Label, Multicenter, Randomised, Controlled Study designed to compare RC48-ADC in Combination With JS001 to Chemotherapy Alone in Previously Untreated HER2-Expressing Unresectable Locally Advanced or Metastatic Urothelial Carcinoma.

Study Overview

• Status: Recruiting
• Conditions: Urothelial Carcinoma; HER2-expressing
• Intervention / Treatment: Drug: RC48-ADC; Drug: Toripalimab; Drug: Gemcitabine; Drug: Cisplatin; Drug: Carboplatin

Detailed Description

This is a Phase 3, Open-Label, Multicenter, Randomised, Controlled Study to evaluate the efficacy and safety of RC48-ADC,a recombinant humanized anti-HER2 monoclonal antibody-Monomethyl auristatin E (MMAE) conjugate, in Combination With JS001,a PD-1 monoclonal antibody, for the treatment of Previously Untreated HER2-Expressing Unresectable Locally Advanced or Metastatic Urothelial Carcinoma.

• Study Type: Interventional
• Enrollment (Estimated): 452
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Jianmin Fang, PhD; Phone Number: +86-010-58075561; Email: jianminfang@hotmail.com

Study Locations

• China
  • Beijing, China
    • Recruiting
    • Beijing Cancer Hospital
    • Contact: Jun Guo
  • Beijing
    • Beijing, Beijing, China
      • Recruiting
      • Cancer Hospital Chinese Academy of Medical Sciences
      • Contact: Aiping zhou

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Expected survival ≥12 weeks.
• Locally advanced unresectable or metastatic UC with histopathological confirmation, including UC originating from the renal pelvis, ureters, bladder, or urethra.
• Participants must not have received prior systemic therapy for locally advanced or metastatic urothelial carcinoma with the following exceptions:

Participants that received neoadjuvant chemotherapy with recurrence >6 months from completion of therapy are permitted; Participants that received adjuvant chemotherapy following cystectomy with recurrence >6 months from completion of therapy are permitted.

• At least one measurable lesion based on RECIST version 1.1
• HER2-expressing status determined by the central laboratory to be IHC 1+, 2+ or 3+.
• ECOG performance status score: 0 or 1.
• Adequate cardiac, bone marrow, hepatic, renal, and coagulation functions.

Exclusion Criteria:

• Known hypersensitivity to RC48-ADC or Toripalimab or any of its components.
• History of major surgery within 4 weeks of planned start of trial treatment.
• Toxicity from a previous treatment has not returned to Grade 0-1.
• Prior ADCs or PD-1/PD-L1 inhibitor therapy.
• Active central nervous system (CNS) metastases.
• Known active hepatitis B, active hepatitis C, or human immunodeficiency virus (HIV) infection.
• History of other malignancy within the previous 5 years, except for low-risk localized prostate cancer, appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, or cancers with a similar curative outcome as those mentioned above.
• Other serious, uncontrolled concomitant diseases that may affect protocol compliance or interpretation of outcomes, including active opportunistic infections or advanced (severe) infections, or uncontrolled diabetes.
• Active autoimmune diseases that require systemic therapy over the past 2 years. Replacement therapies (such as thyroxine, insulin, or physiological replacement of glucocorticoids due to renal or pituitary deficiency) are allowed.
• Assessed by the investigator to be unable or unwilling to comply with the requirements of the protocol.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: RC48-ADC + JS001; Participants will receive RC48-ADC + JS001 every 2 weeks (Q2W) until investigator assessed loss of clinical benefit, unacceptable toxicity, investigator or participant decision to withdraw from therapy, or death (whichever occurs first).	Drug: RC48-ADC; 2.0 mg/kg IV every 2 weeks; Other Names: Disitamab Vedotin; Drug: Toripalimab; 3.0 mg/kg IV every 2 weeks; Other Names: JS001
Active Comparator: Gemcitabine + cisplatin/carboplatin; Participants will receive Gemcitabine + cisplatin or carboplatin every 3 weeks (Q3W) for maximum 6 weeks or until investigator assessed loss of clinical benefit, unacceptable toxicity, investigator or participant decision to withdraw from therapy, or death (whichever occurs first).	Drug: Gemcitabine; 1000mg/m2 IV infusion on Days 1 and 8 of every 3 week cycle; Drug: Cisplatin; 70mg/m2 IV infusion on Day 1 of every 3 week cycle; Drug: Carboplatin; AUC=4.5, IV infusion on Day 1 of every 3 week cycle

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival (PFS), evaluated by independent review committee	Progression-free survival (PFS) refers to the time from the date of randomization to the first researcher's evaluation of disease progression or death (calculated by the event that occurred first). The disease progression will be evaluated by independent review committee according to the RECIST 1.1 standard.	Up to approximately 3 years
Overall survival (OS)	Overall survival (OS) refers to the time from the date of randomization to the date of death of the subject.	Up to approximately 3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective remission rate (ORR)	The objective response rate will be mainly analyzed by the independent efficacy evaluation committee according to the RECIST 1.1 standard tumor evaluation (the evaluation by the investigator will also be performed).	Up to approximately 3 years
Progression-free survival (PFS), evaluated by the investigator	Progression-free survival (PFS) refers to the time from the date of randomization to the first researcher's evaluation of disease progression or death (calculated by the event that occurred first). The disease progression will be evaluated by the researchers according to the RECIST 1.1 standard.	Up to approximately 3 years
Duration of relief (DOR)	DOR is defined as the time from the first documented objective response (CR or PR) to the first documented disease progression or death	Up to approximately 3 years
Disease control rate (DCR)	Disease control rate (DCR) is defined as cases where objective remission (assessed as complete remission or partial remission according to RECIST 1.1 standard) or stable disease during the study.	Up to approximately 3 years

Collaborators and Investigators

• Sponsor: RemeGen Co., Ltd.
• Investigators: Study Director: Na Su, PhD, RemeGen Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): June 14, 2022
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): April 30, 2028

Study Registration Dates

• First Submitted: March 21, 2022
• First Submitted That Met QC Criteria: March 21, 2022
• First Posted (Actual): March 31, 2022

Study Record Updates

• Last Update Posted (Actual): December 18, 2023
• Last Update Submitted That Met QC Criteria: December 15, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: Urothelial Carcinoma; First-Line; HER2-expressing; RC48
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Carcinoma; Carcinoma, Transitional Cell; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunologic Factors; Immunoconjugates; Carboplatin; Gemcitabine; Disitamab vedotin
• Other Study ID Numbers: RC48-C016

Drug and device information, study documents

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