Clinical trial NCT04749485: A Study of HX008 for the Treatment of Patients With Malignant Melanoma
Official title: 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.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Melanoma
Lead sponsor: Taizhou Hanzhong biomedical co. LTD
Sponsor class: INDUSTRY
First posted: 2021-02-11
Enrollment: 119
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Objective Response Rate (ORR)
timeFrame: 24 months
measure: Number of participants with treatment-related adverse events as assessed by CTCAE v5.0
timeFrame: 36 months
Secondary outcomes:
measure: Progression-Free Survival (PFS)
timeFrame: 24 months
measure: Duration of Response (DOR)
timeFrame: 24 months
measure: Overall survival (OS)
timeFrame: 36 months
Other outcomes:
Locations:
city: Beijing
country: China
facility: Peking University Cancer Hospital and Research Institute
state: Beijing
city: Fuzhou
country: China
facility: Fujian Cancer Hospital
state: Fujian
city: Guangzhou
country: China
facility: The First Affiliated Hospital of Jinan University
state: Guangdong
city: Zhengzhou
country: China
facility: The First Affiliated Hospital of Zhengzhou University
state: Henan
city: Nanjing
country: China
facility: Nanjing Drum Tower Hospital
state: Jiangsu
city: Changchun
country: China
facility: The first Hospital of Jilin University
state: Jilin
city: Shanghai
country: China
facility: Fudan Universtiy Shanghai Cancer Center
state: Shanghai
city: Shanghai
country: China
facility: Shanghai Tenth People's Hospital
state: Shanghai
city: Chengdu
country: China
facility: West China Hospital Sichuan Universtiy
state: Sichuan
city: Ürümqi
country: China
facility: The Affiliated Cancer Hospital of Xinjiang Medical University
state: Xinjiang
city: Hangzhou
country: China
facility: Zhejiang University School of Medicine Sir Run Run Shaw Hospital
state: Zhejiang
Study officials:
affiliation: Peking University Cancer Hospital and Research Institute
name: Jun Guo, MD
role: STUDY_CHAIR
References: