A Phase II Study of RC48-ADC in Subjects With HER2 Positive Metastatic or Unresectable Urothelial Cancer

A Multicenter, Open Label，Single Arm，Phase II Study to Evaluate the Effect and Safety of Recombinant Humanized Anti-HER2 Monoclonal Antibody-MMAE Conjugate For Injection in Subjects With HER2 Positive Metastatic or Unresectable Urothelial Cancer

This study will evaluate the efficacy and safety of intravenous RC48-ADC in patients with local advanced or metastatic HER2 positive endothelial cancer.

Inclusion Criteria:

• Voluntary agreement to provide written informed consent.
• Male or female, Age ≥ 18 years and < 80 years.
• Predicted survival ≥ 12 weeks.
• Have histologically or cytologically-confirmed diagnosis of inoperable, locally advanced or metastatic urothelial cancer of the bladder, renal pelvis, ureter.
• Have had progression or intolerance following receipt of at least one systemic chemotherapy for advanced or metastatic disease.
• Measurable disease according to RECIST 1.1.
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1.
• HER2-positive status confirmed by the central laboratory: IHC 2+ or 3+; Subject is able to provide specimens from primary or metastatic lesions for HER2 tests
• Adequate organ function, evidenced by the following laboratory results:

Cardiac ejection fraction ≥ 50 %. Hemoglobin ≥ 9g/dL; Absolute neutrophil count ≥ 1.5×109 /L Platelets ≥ 100×109 /L; Total bilirubin ≤ 1.5× ULN; Without liver metastasis: ALT and AST ≤ 2.5 x ULN; With liver metastasis: ALT and AST ≤ 5 x ULN; Serum creatinine ≤1.5×ULN or creatinine clearance (CrCl) ≥ 50 mL/min as calculated by the Cockcroft-Gault equation.

• 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 Recombinant Humanized Anti-HER2 Monoclonal Antibody-MMAE Conjugate For Injection.
• History of receiving any anti-cancer drug/biologic treatment within 4 weeks prior to trial treatment.
• History of receiving Recombinant Humanized Anti-HER2 Monoclonal Antibody-MMAE Conjugate For Injection.
• 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.
• 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.
• Pregnancy or lactation.
• Assessed by the investigator to be unable or unwilling to comply with the requirements of the protocol.