NCT05302284

Brief Summary

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.

Trial Health

77
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
452

participants targeted

Target at P50-P75 for phase_3

Timeline
25mo left

Started Jun 2022

Longer than P75 for phase_3

Geographic Reach
1 country

2 active sites

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress66%
Jun 2022Apr 2028

First Submitted

Initial submission to the registry

March 21, 2022

Completed
10 days until next milestone

First Posted

Study publicly available on registry

March 31, 2022

Completed
3 months until next milestone

Study Start

First participant enrolled

June 14, 2022

Completed
4.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 31, 2026

Expected
1.3 years until next milestone

Study Completion

Last participant's last visit for all outcomes

April 30, 2028

Last Updated

December 18, 2023

Status Verified

December 1, 2023

Enrollment Period

4.6 years

First QC Date

March 21, 2022

Last Update Submit

December 15, 2023

Conditions

Urothelial CarcinomaHER2-expressing

Keywords

Urothelial CarcinomaHER2-expressingRC48First-Line

Outcome Measures

Primary Outcomes (2)

  • 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 Outcomes (4)

  • Objective remission rate (ORR)

    Up to approximately 3 years

  • Progression-free survival (PFS), evaluated by the investigator

    Up to approximately 3 years

  • Duration of relief (DOR)

    Up to approximately 3 years

  • Disease control rate (DCR)

    Up to approximately 3 years

Study Arms (2)

RC48-ADC + JS001

EXPERIMENTAL

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-ADCDrug: Toripalimab

Gemcitabine + cisplatin/carboplatin

ACTIVE COMPARATOR

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: GemcitabineDrug: CisplatinDrug: Carboplatin

Interventions

RC48-ADCDRUG

2.0 mg/kg IV every 2 weeks

Also known as: Disitamab Vedotin
RC48-ADC + JS001
ToripalimabDRUG

3.0 mg/kg IV every 2 weeks

Also known as: JS001
RC48-ADC + JS001
GemcitabineDRUG

1000mg/m2 IV infusion on Days 1 and 8 of every 3 week cycle

Gemcitabine + cisplatin/carboplatin
CisplatinDRUG

70mg/m2 IV infusion on Day 1 of every 3 week cycle

Gemcitabine + cisplatin/carboplatin
CarboplatinDRUG

AUC=4.5, IV infusion on Day 1 of every 3 week cycle

Gemcitabine + cisplatin/carboplatin

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (2)

Cancer Hospital Chinese Academy of Medical Sciences

Beijing, Beijing Municipality, China

RECRUITING

Beijing Cancer Hospital

Beijing, China

RECRUITING

Related Publications (1)

  • Sheng X, Zeng G, Zhang C, Zhang Q, Bian J, Niu H, Li J, Shi Y, Yao K, Hu B, Liu Z, Liao H, Yu Z, Jin B, Zhao P, Yang T, Liu X, Qin Y, Xue X, Gou X, Huang J, Gu J, Qi X, Zhang L, Ma G, Liu B, Fang J, Jiang S, He Z, Zhou A, Guo J; RC48-C016 Trial Investigators. Disitamab Vedotin plus Toripalimab in HER2-Expressing Advanced Urothelial Cancer. N Engl J Med. 2025 Dec 11;393(23):2324-2337. doi: 10.1056/NEJMoa2511648. Epub 2025 Oct 19.

    PMID: 41124210DERIVED

MeSH Terms

Conditions

Carcinoma, Transitional Cell

Interventions

disitamab vedotintoripalimabGemcitabineCisplatinCarboplatin

Condition Hierarchy (Ancestors)

CarcinomaNeoplasms, Glandular and EpithelialNeoplasms by Histologic TypeNeoplasms

Intervention Hierarchy (Ancestors)

Heterocyclic CompoundsDeoxycytidineCytidinePyrimidine NucleosidesPyrimidinesHeterocyclic Compounds, 1-RingChlorine CompoundsInorganic ChemicalsNitrogen CompoundsPlatinum CompoundsCoordination ComplexesOrganic Chemicals

Study Officials

  • Na Su, PhD

    RemeGen Co., Ltd.

    STUDY DIRECTOR

Central Study Contacts

Jianmin Fang, PhD

CONTACT

+86-010-58075561jianminfang@hotmail.com

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

March 21, 2022

First Posted

March 31, 2022

Study Start

June 14, 2022

Primary Completion (Estimated)

December 31, 2026

Study Completion (Estimated)

April 30, 2028

Last Updated

December 18, 2023

Record last verified: 2023-12

Locations

CN(2)