A Study of RC48-ADC(Antibody Drug Conjugate) and JS001 to Evaluate the Safety and Pharmacokinetics of Subjects With Locally Advanced or Metastatic Urothelial Cancer

Inclusion Criteria:

• Signed informed consent form; Aged 18 years and above; ECOG(Eastern CooperativeOncology Group) performance is 0 or 1; Life expectancy greater than 12 weeks; Patientswith locally advanced or metastatic malignant urothelial carcinoma which is platinumnaive and cisplatin ineligible, or progressed after at least one line standardsystemic chemotherapy (including progression within 12 months of neo-/adjuvanttherapy); Cisplatinum ineligible patients should meet one of the following criteria:

1. Aged 70 years and above, and ECOG performance is 1;

2. Serum creatinine >= 1.0xULN or CrCl＜60ml/min;

3. Lose of hearing >= Grade 2;

4. Peripheral nerve disorder >= Grade 2 Patients with measurable and appreciable tumorlesions according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1);Willing to provide primary lesion samples for the purpose of PD-L1 and HER2 tests. Adequate organ function as defined by the following criteria:

5. absolute neutrophil count(ANC) >= 1.5 x 10^9/L;

6. platelets>=100* 10^9/L;

7. Total serum creatinine <=1.5*ULN;

8. serum aspartate transaminase (AST) and serum alanine transaminase (ALT) <=2.5upperlimit of normal (ULN), or AST and ALT<=5ULN if liver function abnormalities are dueto underlying malignancy; normal serum creatinine ;

9. Left ventricular ejection fraction (LVEF) ＞=50%

10. Hemoglobin＞=9g/dl Women of child-bearing potential and men must agree to use adequatecontraception (e.g., condoms, implants, injectables, combined oral contraceptives,some intrauterine devices [IUDs], complete sexual abstinence, or sterilized partner)prior to study entry and during the period of therapy and for 30 days after the lastdose of study drug;

Exclusion Criteria:

• Allergy to RC48-ADC, or JS001, or their components Received anti-cancer therapyincluding chemotherapy, radiotherapy, immunotherapy or other clinical trial treatmentswithin 3 weeks of starting study treatment Unresolved toxicities from prioranti-cancer therapy, except for alopecia Previously treated with HER2-ADC and/oranti-PD-1 or anti-PD-L1 or anti PD-L2 therapies; Underwent major surgery within 4weeks of first dose of study drug and not completely recovered; Received vaccinewithin 4 weeks of first dose of study drug Currently active clinically significantcardiovascular disease such as uncontrolled arrhythmia, congestive heart failure, orgreater than or equal to Class 2 congestive heart failure as defined by the New YorkHeart Association Functional Classification, or history of myocardial infarctionunstable angina, or acute coronary syndrome within 6 months prior to enrollment in thestudy; History of other neoplastic disease within 3 years prior to the study drug,with exception of resolved/curable cancers such as basal skin cancer or squamous cellskin cancer,. Metastasis to CNS(central nervous system) and/or carcinomatous meningitis, with exceptionfor the patients who received treatment of metastasis to CNS and/or carcinomatousmeningitis and had stable disease for at least 3 months, and no evidence of progressionwithin 4 weeks of first dose of study treatment. No evidence of new or expanded metastasis,and untreated with radiotherapy, surgery or steroid therapy within 4 weeks of first dose ofstudy treatment. History of allogeneic hematopoietic stem cell transplantation or organ transplantation;Patients who had received systemic steroid therapy within the last 2 years; Pregnancy orlactation; Positive results of HIV testing; Active HBV(hepatitis B virus) or HCV(hepatitisC virus) infection Active tuberculosis; Other disorders with clinical significanceaccording to the researcher's judgment; Unwilling or unable to participate in all requiredstudy evaluations and procedures