A Study of HX008 Plus LP002 for the Treatment of Patients With Advanced Melanoma

Inclusion Criteria:

• Provide written informed consent voluntarily. Understand this protocol and be willingand able to adhere to the study visit schedule.
• Male and Female aged 18 to 75 are eligible.
• Histologic diagnosis of locally advanced or metastatic melanoma, who are unable toundergo complete resection, while ocular melanoma is excluded, and the overall rate ofmucosal melanoma is no more than 22%.
• Has experienced progressed disease in previous anti-PD-1 or PD-L1 therapy for thelocally advanced or metastatic melanoma (anti-PD-1 or PD-L1 therapy as neo-adjuvant oradjuvant therapy could be accepted if progressed disease occured with 6 months afterthe last dose of treatment).
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1.
• Life expectancy ≥ 3 months.
• With at least 1 measurable extracranial lesion based on RECIST v1.1, and no previousradiotherapy administrated to the measurable lesions.
• Central nervous system metastases must be asymptomatic with or without treatment, andbe stable for at least 3 months based on CT/MRI, and no need for systemic steroidswithin 4 weeks prior to the first dose of the study drug.
• Provide with tumor specimen (for testing the expression of PD -L1).
• Has sufficient organ and bone marrow function to meet the following laboratoryexamination standards (without blood transfusion within 14 days prior to enrollment):neutrophils ≥ 1.5 x 10^9/L; white blood cells ≥3.0 x 10^9/L; platelets ≥ 100 x 10^9/L;hemoglobin ≥ 90 g/L; serum creatinine ≤1.5x ULN; aspartic transaminase (AST) andalanine transaminase (ALT) ≤ 2.5 x ULN without, and ≤ 5 x ULN with hepatic metastasis;total bilirubin ≤ 1.5 x ULN; INR≤2 x ULN, aPTT≤1.5 x ULN (except for those undergoinganticoagulant therapy).
• Reproductive men and women of childbearing age are willing to take effectivecontraceptive measures from signing the informed consent form to 3 months after thelast administration of the trial drug.

Exclusion Criteria:

• Prior malignancy active within the previous 5 years except for locally curable cancersthat have been apparently cured, such as carcinoma in situ of the cervix or basal cellskin cancer.
• Has experienced severe immunotherapy related toxicity in the previous anti-PD-1 /PD-L1 monoclonal antibody treatment, including but not limited to: Grade 3 / 4pneumonia, proteinuria, uveitis or upper scleritis, myasthenia gravis, pancreatitis,hepatitis, bullous skin diseases (including SJS, TEN); grade 2-4 encephalitis,myocarditis; any grade of Guillain Barre syndrome, transverse myelitis; severeinflammatory arthritis that significantly impact the quality of patient's life;
• Known to has BRAF V600 mutation before signing informed consent form, and has notreceived any corresponding targeted therapy.
• With adverse reactions of previous treatment that have not recovered to CTCAE V5.0grade ≤ 1, except for the residual hair loss effect.
• With active or history of autoimmune diseases that may recur (e.g., systemic lupuserythematosus, rheumatoid arthritis, inflammatory bowel disease, autoimmune thyroiddisease, multiple sclerosis, vasculitis, glomerulitis, etc.), or patients with highrisk (e.g., organ transplantation requiring immunosuppressive therapy). While thosewith the following diseases were allowed to be enrolled: a) Stable patients with typeI diabetes after a fixed dose of insulin; b) Autoimmune hypothyroidism requiringhormone replacement therapy only; c) Skin diseases requiring no systemic treatment (e.g. eczema, skin rash covering less than 10% of the body surface, psoriasis withoutophthalmic symptoms, etc.).
• Expecting to receive major surgery during the study period including 4 weeks prior tothe first dose of the study drug.
• Need to receive systemic corticosteroids (dose equivalent to > 10 mg prednisone / day)or other immunosuppressive drugs within 14 days before enrollment or during the studyperiod. Those under the following conditions are eligible: a) Locally external use orinhaled corticosteroids; b) short-term (≤ 7 days) use of glucocorticoids for theprevention or treatment of non autoimmune allergic diseases.
• Has active digestive ulcer, incomplete intestinal obstruction, active gastrointestinalhemorrhage or perforation.
• Has active interstitial pneumonia, pulmonary fibrosis, acute pulmonary disorders, etal.
• Has uncontrolled systemic diseases, for instance, cardiovascular and cerebrovasculardisease, diabetes, hypertension, tuberculosis.
• History of human immunodeficiency virus infection, acquired or congenitalimmunodeficiency disease, organ transplantation or stem cell transplantation.
• Has active chronic HBV or HCV infection, except those with HBV DNA viral load ≤500IU/mL or <10^3 copies/mL, or HCV RNA negative after adequate treatment.
• Has severe infection within 4 weeks or active infection requiring IV infusion or oraladministration of antibiotics within 2 weeks prior to the first dose of the studydrug.
• Known to be allergic to macromolecular protein agents or monoclonal antibody; Known tohas a history of severe allergies (CTCAE v5.0 ≥ grade 3) to any of the components inthe study drug.
• Has participated in other clinical trial within 4 weeks prior to the first dose of thestudy drug.
• Alcohol dependence or drug abuse within recent one year.
• Has a history of confirmed neurological or mental disorders, such as epilepsy,dementia; or with poor compliance; or the presence of peripheral neurologicaldisorders.
• Is pregnant or breastfeeding.
• Has received a live vaccine within 30 days prior to the first dose of trial treatment.
• Other reasons disqualifying the entering of this study based on the evaluation of theinvestigators.