A Study of HX008 for the Treatment of Patients With Malignant Melanoma

Study Overview
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Brief Summary
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HX008 is a humanized monoclonal antibody targeting PD-1 on T cell surface, restores T cell activity, thus enhancing immune response and has potential to treat various types of tumors. In this study, the efficacy and safety of HX008 in patients with locally advanced or metastatic melanoma who have failed the standard treatments will be evaluated.

Official Title
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A Single-armed Open-labeled Phase II Study of HX008 (a Humanized Monoclonal Antibody Targeting PD-1) for the Treatment of Patients With Locally Advanced or Metastatic Melanoma Who Have Failed the Standard Treatments.

Conditions
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Melanoma

Intervention / Treatment
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* Drug: HX008


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Provide written informed consent voluntarily. Understand this protocol and be willing and able to adhere to the study visit schedule; Male and Female aged 18 to 75 are eligible; Histologic diagnosis of locally advanced unable to undergo complete resection or metastatic melanoma, while ocular melanoma is excluded, and the overall rate of mucosal melanoma is no more than 22%. Has failed at least 1 prior routine regimen for advanced disease, including chemotherapy, target therapy, immunotherapy, biological therapy (IFN-gamma, interleukin, onco-vaccine, cytokine, oncolytic virus or cancer growth factor inhibition), and the interval between last previous treatment and the first dose of this trial should be ≥ 4 weeks or 5 half-life of the previously administrated drug, which happens first. Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1. Life expectancy ≥ 3 months. At least 1 measurable extracranial lesion based on RECIST v1.1, and no prior radiation to measurable lesions; Central nervous system metastases must be asymptomatic with or without treatment, and be stable for at least 3 months based on CT/MRI, and no need for systemic steroids within 4 weeks prior to the first dose of the study drug. Providing with tumor specimen (for testing the expression of PD -L1); Has sufficient organ and bone marrow function to meet the following laboratory examination standards: 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 ≤1x ULN; aspartic transaminase (AST) and alanine 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 undergoing anticoagulant therapy); Reproductive men and women of childbearing age are willing to take effective contraceptive measures from signing the informed consent form to 3 months after the last administration of the trial drug. Exclusion Criteria: Prior malignancy active within the previous 5 years except for locally curable cancers that have been apparently cured, such as carcinoma in situ of the cervix or basal cell skin cancer. With adverse reactions of previous treatment that have not recovered to CTCAE V5.0 grade ≤ 1, except for the residual hair loss effect. Prior treatment with anti-PD-1/PD-L1/CTLA-4 antibody. With active or history of autoimmune diseases that may recur (e.g., systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, autoimmune thyroid disease, multiple sclerosis, vasculitis, glomerulitis, etc.), or patients with high risk (e.g., organ transplantation requiring immunosuppressive therapy). While those with the following diseases were allowed to be enrolled: a) Stable patients with type I diabetes after a fixed dose of insulin; b) Autoimmune hypothyroidism requiring hormone replacement therapy only; c) Skin diseases requiring no systemic treatment (e.g. eczema, skin rash covering less than 10% of the body surface, psoriasis without ophthalmic symptoms, etc.). Expecting to receive major surgery during the study period including 4 weeks prior to the 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 study period. Those under the following conditions are eligible: a) Locally external use or inhaled corticosteroids; b) short-term (≤ 7 days) use of glucocorticoids for the prevention or treatment of non-autoimmune allergic diseases. History of human immunodeficiency virus infection, acquired or congenital immunodeficiency disease, organ transplantation or stem cell transplantation. Has active chronic HBV or HCV infection, except those with HBV DNA viral load ≤500 IU/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 oral administration of antibiotics within 2 weeks prior to the first dose of the study drug. Known to be allergic to macromolecular protein agents or monoclonal antibody; Known to has a history of severe allergies to any of the components in the study drug (CTCAE v5.0 ≥ grade 3); Has participated in other clinical trial within 4 weeks prior to the first dose of the study 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 neurological disorders. Has brain metastasis with symptoms. Is pregnant or breastfeeding. Other reasons disqualifying the entering of this study based on the evaluation of the investigators.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: HX008<br> | Drug: HX008<br>* Patients will receive HX008 3mg/kg by intravenous (IV) infusion on Day 1, every 3 weeks (Q3W), till progressed disease or withdrawal.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) | Percentage of subjects achieving complete response (CR) and partial response (PR). | 24 months | 
| Number of participants with treatment-related adverse events as assessed by CTCAE v5.0 |  | 36 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-Free Survival (PFS) | Progression-free survival (PFS) is defined as the time from the first study drug treatment to disease progression (PD) or to death of the subject due to any reason. | 24 months | 
| Duration of Response (DOR) | Duration of Response (DOR) is defined as the time from the first evidence of response (PR or CR) to the first evidence of PD or the date of death for any reason. | 24 months | 
| Overall survival (OS) | Overall survival (OS) refers to the time from the first study drug treatment to death due to any cause. | 36 months |