A Open-label, Single-arm, Multicenter, Phase II Study of RC48-ADC to Evaluate the Efficacy and Safety of Subjects With HER2 Overexpressing Locally Advanced or Metastatic Urothelial Cancer

Study Overview
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Brief Summary
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This study will evaluate the efficacy and safety of intravenous RC48-ADC in patients with HER2 overexpressing locally advanced or metastatic urothelial cancer.

Official Title
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A Open-label, Single-arm, Multicenter, Phase II Study of RC48-ADC to Evaluate the Efficacy and Safety of Subjects With HER2 Overexpressing Locally Advanced or Metastatic Urothelial Cancer

Conditions
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Urothelial Carcinoma

Intervention / Treatment
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* Drug: RC48-ADC


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Voluntary agreement to provide written informed consent. Male or female, Age ≥ 18 years. Predicted survival ≥ 12 weeks. Diagnosed with histologically or cytologically-confirmed locally advanced or metastatic urothelial cancer, originate from bladder, renal pelvis, ureter and urinary tract. Unresectable or disease progression (i.e. locally advanced/metastasis) after surgery and at least regular chemotherapy including gemcitabine,cisplatin AND paclitaxel. Disease progression within 6 months of the completion of neo-adjuvant and adjuvant chemotherapy with gemcitabine, cisplatin AND paclitaxel is also eligible. Measurable lesion according to RECIST 1.1. HER2 overexpressing (i.e. IHC 2+ or 3+) as confirmed by the central lab. Primary or metastatic tumor sample will be provided for HER2 test. Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1. Adequate organ function, evidenced by the following laboratory results within 7 days prior to the study treatment: Cardiac ejection fraction ≥ 50 %. Hemoglobin ≥ 9g/dL; Absolute neutrophil count ≥ 1.5×109 /L Platelets ≥ 100×109 /L; Total bilirubin ≤ 1.5× ULN; AST and ALT ≤ 2.5×ULN and ≤ 5 × ULN with hepatic metastasis; Serum creatinine ≤1.5×ULN. All female subjects will be considered to be of child-bearing potential unless they are postmenopausal, or have been sterilized surgically.Female subjects of child-bearing potential must agree to use two forms of highly effective contraception. Male subjects and their female partner who are of child-bearing potential must agree to use two forms of highly effective contraception. Willing to adhere to the study visit schedule and the prohibitions and restrictions specified in this protocol. Exclusion Criteria: Known hypersensitivity to the components of Recombinant Humanized Anti-HER2 Monoclonal Antibody-MMAE Conjugate. Toxicity of previous anti-tumor treatment not recovered to CTCAE Grade 0-1 (with exception of Grade 2 alopecia). Pleural or abdominal effusion with clinical symptoms that requires ongoing treatment. History of major surgery within 4 weeks of planned start of trial treatment. Has received a live virus vaccine within 4 weeks of planned start of trial treatment. Currently known active infection with HIV or tuberculosis. Diagnosed with HBsAg, HBcAb positive and HBV DNA copy positive, or HCVAb positive. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator. History of other malignancy within the previous 5 years, except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, or cancers with a similar curative outcome as those mentioned above. known central nervous system metastases. Uncontrolled hypertension, diabetes, Interstitial lung Disease, or COPD; Treated with systemic treatment (e.g. immunomodulators, corticosteroids or immunosuppressants) for the autoimmune disease within 2 years prior to the study treatment. NYHA Class III heart failure. Pregnancy or lactation. Assessed by the investigator to be unable or unwilling to comply with the requirements of the protocol.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: RC48-ADC<br>Participants will be treated with RC48-ADC 2.0 mg/kg, once every 2 weeks (Q2W) until investigator-assessed loss of clinical benefit, unacceptable toxicity, investigator or participant's decision to withdraw from therapy, or death (whichever occurs first). | Drug: RC48-ADC<br>* 2.0mg/kg IV every 2 weeks<br>* Other names: Recombinant Humanized anti-HER2 Monoclonal Antibody-MMAE Conjugate For Injection;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate （ORR）as assessed by the Independent Review Committee | Objective Response Rate was defined as the percentage of participants with a complete response (CR) or partial response (PR) | 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate（ORR）as assessed by investigator | Objective Response Rate was defined as the percentage of participants with a complete response (CR) or partial response (PR) | 24 months | 
| Progression Free Survival (PFS) | PFS was defined as the time from the first administration of study treatment to the first occurrence of disease progression as determined by investigator using RECIST v1.1 or death from any cause, whichever comes first | 24 months | 
| Duration of Objective Response (DOR) | DOR was defined as the time from first documented OR to first documented PD or death from any cause, whichever occurred earlier | 24 months | 
| Disease control rate (DCR) | DCR was defined as the percentage of participants with a complete response (CR), partial response (PR), or stable disease (SD) | 24 months | 
| Overall survival (OS) | OS was defined as the time from the first administration of study treatment to death from any cause. | 24 months |