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

NCT ID: NCT05302284

Last Updated: 2023-12-18

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE3

Total Enrollment

452 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-06-14

Study Completion Date

2028-04-30

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Urothelial Carcinoma HER2-expressing

Keywords

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Urothelial Carcinoma HER2-expressing RC48 First-Line

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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).

Group Type EXPERIMENTAL

RC48-ADC

Intervention Type DRUG

2.0 mg/kg IV every 2 weeks

Toripalimab

Intervention Type DRUG

3.0 mg/kg IV every 2 weeks

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).

Group Type ACTIVE_COMPARATOR

Gemcitabine

Intervention Type DRUG

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

Cisplatin

Intervention Type DRUG

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

Carboplatin

Intervention Type DRUG

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

Interventions

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RC48-ADC

2.0 mg/kg IV every 2 weeks

Intervention Type DRUG

Toripalimab

3.0 mg/kg IV every 2 weeks

Intervention Type DRUG

Gemcitabine

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

Intervention Type DRUG

Cisplatin

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

Intervention Type DRUG

Carboplatin

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

Intervention Type DRUG

Other Intervention Names

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Disitamab Vedotin JS001

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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RemeGen Co., Ltd.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Na Su, PhD

Role: STUDY_DIRECTOR

RemeGen Co., Ltd.

Locations

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Cancer Hospital Chinese Academy of Medical Sciences

Beijing, Beijing Municipality, China

Site Status RECRUITING

Beijing Cancer Hospital

Beijing, , China

Site Status RECRUITING

Countries

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China

Central Contacts

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Jianmin Fang, PhD

Role: CONTACT

Phone: +86-010-58075561

Email: [email protected]

Facility Contacts

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Aiping zhou

Role: primary

Jun Guo

Role: primary

References

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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 Oct 19. doi: 10.1056/NEJMoa2511648. Online ahead of print.

Reference Type DERIVED
PMID: 41124210 (View on PubMed)

Other Identifiers

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RC48-C016

Identifier Type: -

Identifier Source: org_study_id