A Randomized, Controlled, Multi-center, Phase III Clinical Study to Investigate Recombinant Humanized PD-1 Monoclonal Antibody Injection (JS001) Versus Dacarbazine as the 1st-line Therapy for Unresectable or Metastatic Melanoma

Patients are eligible for participation in the trial only when they meet the following criteria:

Age ≥18 years, male or female;

Systemic treatment-naïve, histologically confirmed unresectable stage III or IV melanoma. Previous adjuvant or neoadjuvant therapy is allowed, however, it is required to be completed at least three weeks prior to the randomization, and all the relevant adverse events have been recovered to normal or CTC-AE grade 1;

Measurable lesion (according to RECIST v1.1 criteria);

ECOG score 0 or 1

Tumor tissue has to be provided (FFPE archival or newly acquired tissue block or unstained slide from FFPE) for analysis of biomarkers;

Previous radiotherapy must be completed at least two weeks prior to administration of investigational product;

The laboratory data for screening must meet the following criteria and should be acquired within 14 days prior to the first dose:

1. Peripheral hemogram: white blood cell (WBC) ≥3.0×109/L, neutrophil (ANC) ≥1.5×109/L, platelet (PLT) ≥100×109/L, hemoglobin (Hgb) ≥90g/L;

2. Renal function: serum creatinine°≤1.5 x ULN or calculated creatinine clearance (CrCl) \>40 mL/min (using Cockcroft Gault formula);

3. Hepatic function: AST/ALT≤2.5 x ULN in subjects without hepatic metastasis, AST/ALT≤5 x ULN in those with hepatic metastasis;

4. Total bilirubin ≤1.5 x ULN (except the subjects with Gilbert syndrome, the total bilirubin must be \< 3.0mg/dL).

Estimated survival ≥16 weeks;

Men with reproductive capacity or women of childbearing potential must use highly effective contraceptive methods during the trial (e.g., oral contraceptives, intrauterine device, sexual abstinence or barrier method combined with spermicide), and continue contraception for 12 months after the end of treatment;

Subject is willing to participate in the study, sign the informed consent form with good compliance and cooperation with follow-up;

Re-enrollment: re-enrollment of subjects who discontinue the study for failure prior to the treatment (i.e., the subject has not been randomized/received any treatment yet) is allowed in this study. The subjects must re-sign the informed consent form if they are re-enrolled.

According to investigators' evaluation, the subjects must have documented radiological progression of disease during DTIC treatment;

Previous anticancer therapy, including DTIC and palliative radiotherapy, must be completed at least three weeks prior to the dose of JS001;

Adverse events related with DTIC or palliative radiotherapy must have been relieved to grade 1 or baseline at randomization;

Any major surgery must be completed at least 28 days prior to the first dose of JS001;

No previous treatment with anti-PD-1 or anti-PD-L1 therapy;

The laboratory data on the eligibility for cross-over therapy must meet the following criteria and should be acquired within 14 days prior to the start of JS001 treatment:

Peripheral hemogram: white blood cell (WBC) ≥3.0×109/L, neutrophil (ANC) ≥1.5×109/L, platelet (PLT) ≥100×109/L, hemoglobin (Hgb) ≥90g/L;

Renal function: serum creatinine≤1.5 x ULN or calculated creatinine clearance (CrCl) \>40 mL/min (using Cockcroft Gault formula);

Hepatic function: AST/ALT≤2.5 x ULN in subjects with no hepatic metastasis, AST/ALT≤5 x ULN in those with hepatic metastasis;

Total bilirubin≤1.5 x ULN (except the subjects with Gilbert syndrome, total bilirubin must be\<3.0mg/dL).

Men with reproductive capacity or women of childbearing potential must use highly effective contraceptive methods during the trial (e.g., oral contraceptives, intrauterine device, sexual abstinence or barrier method combined with spermicide), and continue contraception for 12 months after the end of treatment;

Subjects are willing to participate in the study, sign the informed consent form with good compliance and cooperation with follow-up;

What this study is about