Clinical trial NCT05302284: A Study of RC48-ADC Combined With Toripalimab For First-line Treatment of Urothelial Carcinoma
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Urothelial Carcinoma
HER2-expressing
Keywords: Urothelial Carcinoma
HER2-expressing
RC48
First-Line
Lead sponsor: RemeGen Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2022-03-31
Enrollment: 452
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Progression-free survival (PFS), evaluated by independent review committee
timeFrame: Up to approximately 3 years
measure: Overall survival (OS)
timeFrame: Up to approximately 3 years
Secondary outcomes:
measure: Objective remission rate (ORR)
timeFrame: Up to approximately 3 years
measure: Progression-free survival (PFS), evaluated by the investigator
timeFrame: Up to approximately 3 years
measure: Duration of relief (DOR)
timeFrame: Up to approximately 3 years
measure: Disease control rate (DCR)
timeFrame: Up to approximately 3 years
Other outcomes:
Locations:
city: Beijing
country: China
facility: Cancer Hospital Chinese Academy of Medical Sciences
state: Beijing
city: Beijing
country: China
facility: Beijing Cancer Hospital
Study officials:
affiliation: RemeGen Co., Ltd.
name: Na Su, PhD
role: STUDY_DIRECTOR
References: