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

Primary Purpose

Melanoma

Status
Unknown status
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
HX008
LP002
Sponsored by
Taizhou HoudeAoke Biomedical Co., Ltd.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Melanoma

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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 or metastatic melanoma, who are unable to undergo complete resection, while ocular melanoma is excluded, and the overall rate of mucosal melanoma is no more than 22%.
  • Has experienced progressed disease in previous anti-PD-1 or PD-L1 therapy for the locally advanced or metastatic melanoma (anti-PD-1 or PD-L1 therapy as neo-adjuvant or adjuvant therapy could be accepted if progressed disease occured with 6 months after the 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 previous radiotherapy administrated to the 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.
  • Provide with tumor specimen (for testing the expression of PD -L1).
  • Has sufficient organ and bone marrow function to meet the following laboratory examination 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) 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.
  • Has experienced severe immunotherapy related toxicity in the previous anti-PD-1 / PD-L1 monoclonal antibody treatment, including but not limited to: Grade 3 / 4 pneumonia, 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; severe inflammatory arthritis that significantly impact the quality of patient's life;
  • Known to has BRAF V600 mutation before signing informed consent form, and has not received any corresponding targeted therapy.
  • With adverse reactions of previous treatment that have not recovered to CTCAE V5.0 grade ≤ 1, except for the residual hair loss effect.
  • 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.
  • Has active digestive ulcer, incomplete intestinal obstruction, active gastrointestinal hemorrhage or perforation.
  • Has active interstitial pneumonia, pulmonary fibrosis, acute pulmonary disorders, et al.
  • Has uncontrolled systemic diseases, for instance, cardiovascular and cerebrovascular disease, diabetes, hypertension, tuberculosis.
  • 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 (CTCAE v5.0 ≥ grade 3) to any of the components in the study drug.
  • 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.
  • 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 the investigators.

Sites / Locations

  • Beijing Cancer HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm Type

Experimental

Experimental

Experimental

Experimental

Experimental

Arm Label

Ia: LP002 dose escalation-1mg/kg

Ia: LP002 dose escalation-3mg/kg

Ia: LP002 dose escalation-5mg/kg

Ib: Expansion

Ib: Control

Arm Description

3-6 participants will receive HX008 of 200mg, Q3W plus LP002 of 1mg/kg, Q3W for up to 1 year.

3-6 participants will receive HX008 of 200mg, Q3W plus LP002 of 3mg/kg, Q3W for up to 1 year.

3-6 participants will receive HX008 of 200mg, Q3W plus LP002 of 5mg/kg, Q3W for up to 1 year.

Approximately 30 participants will receive HX008 of 200mg, Q3W plus LP002 of the recommended dose, Q3W for up to 1 year.

Approximately 15 participants will receive LP002 of recommended dose, Q3W for up to 1 year.

Outcomes

Primary Outcome Measures

DLT (dose limited toxicity) rate
To observe how many participants experience DLT in each LP002 dose group in phase Ia.
Number of participants with treatment-related adverse events as assessed by CTCAE v5.0
Objective Response Rate (ORR)
Percentage of subjects achieving complete response (CR) and partial response (PR).
Terminal half-life (T1 / 2) of HX008 and LP002
Area under curve (AUC) of HX008 and LP002
Apparent volume of distribution of HX008 and LP002
Systemic clearance of HX008 and LP002
Cmax of HX008 and LP002
Cmin of HX008 and LP002
Tmax of HX008 and LP002

Secondary Outcome Measures

Disease Control Rate (DCR)
Disease Control Rate (DCR) refers to the proportion of subjects who achieve CR, PR and SD through imaging evaluation.
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.
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.
Overall survival (OS)
Overall survival (OS) refers to the time from the first study drug treatment to death due to any cause.

Full Information

First Posted
February 8, 2021
Last Updated
February 12, 2021
Sponsor
Taizhou HoudeAoke Biomedical Co., Ltd.
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1. Study Identification

Unique Protocol Identification Number
NCT04756934
Brief Title
A Study of HX008 Plus LP002 for the Treatment of Patients With Advanced Melanoma
Official Title
A Phase I Study of Tolerance and Pharmacokinetics of HX008 (a Humanized Monoclonal Antibody Targeting PD-1) Plus LP002 (a Humanized Monoclonal Antibody Targeting PD-L1) in Patients With Locally Advanced or Metastatic Melanoma Who Have Experienced Progressed Disease in Previous Anti-PD-1 or PD-L1 Therapy.
Study Type
Interventional

2. Study Status

Record Verification Date
February 2021
Overall Recruitment Status
Unknown status
Study Start Date
August 20, 2020 (Actual)
Primary Completion Date
August 20, 2021 (Anticipated)
Study Completion Date
August 20, 2022 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Taizhou HoudeAoke Biomedical Co., Ltd.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
The subsequent treatment choices for the patients with advanced melanoma, who have failed the immune checkpoint inhibitor therapy of single agent. Evidences showed that PD-1 and PD-L1 signalling pathways are not redundant. Blocking both of them could produce synergistic effect. HX008 and LP002 are humanized monoclonal antibodies targeting PD-1 on T cells and PD-L1 on tumor cells respectively. In this study, participants with locally advanced or metastatic melanoma who have failed previous anti-PD-1 or PD-L1 will be administrated with HX008 plus LP002. The safety and preliminary efficacy will be evaluated.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Melanoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
63 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Ia: LP002 dose escalation-1mg/kg
Arm Type
Experimental
Arm Description
3-6 participants will receive HX008 of 200mg, Q3W plus LP002 of 1mg/kg, Q3W for up to 1 year.
Arm Title
Ia: LP002 dose escalation-3mg/kg
Arm Type
Experimental
Arm Description
3-6 participants will receive HX008 of 200mg, Q3W plus LP002 of 3mg/kg, Q3W for up to 1 year.
Arm Title
Ia: LP002 dose escalation-5mg/kg
Arm Type
Experimental
Arm Description
3-6 participants will receive HX008 of 200mg, Q3W plus LP002 of 5mg/kg, Q3W for up to 1 year.
Arm Title
Ib: Expansion
Arm Type
Experimental
Arm Description
Approximately 30 participants will receive HX008 of 200mg, Q3W plus LP002 of the recommended dose, Q3W for up to 1 year.
Arm Title
Ib: Control
Arm Type
Experimental
Arm Description
Approximately 15 participants will receive LP002 of recommended dose, Q3W for up to 1 year.
Intervention Type
Drug
Intervention Name(s)
HX008
Intervention Description
HX008: 200mg, Q3W
Intervention Type
Drug
Intervention Name(s)
LP002
Intervention Description
LP002: 1mg/kg, or 3mg/kg, or 5mg/kg, Q3W
Primary Outcome Measure Information:
Title
DLT (dose limited toxicity) rate
Description
To observe how many participants experience DLT in each LP002 dose group in phase Ia.
Time Frame
6 months
Title
Number of participants with treatment-related adverse events as assessed by CTCAE v5.0
Time Frame
2 years
Title
Objective Response Rate (ORR)
Description
Percentage of subjects achieving complete response (CR) and partial response (PR).
Time Frame
1 year
Title
Terminal half-life (T1 / 2) of HX008 and LP002
Time Frame
1 year
Title
Area under curve (AUC) of HX008 and LP002
Time Frame
1 year
Title
Apparent volume of distribution of HX008 and LP002
Time Frame
1 year
Title
Systemic clearance of HX008 and LP002
Time Frame
1 year
Title
Cmax of HX008 and LP002
Time Frame
1 year
Title
Cmin of HX008 and LP002
Time Frame
1 year
Title
Tmax of HX008 and LP002
Time Frame
1 year
Secondary Outcome Measure Information:
Title
Disease Control Rate (DCR)
Description
Disease Control Rate (DCR) refers to the proportion of subjects who achieve CR, PR and SD through imaging evaluation.
Time Frame
1 year
Title
Duration of Response (DOR)
Description
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.
Time Frame
2 years
Title
Progression-Free Survival (PFS)
Description
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.
Time Frame
2 years
Title
Overall survival (OS)
Description
Overall survival (OS) refers to the time from the first study drug treatment to death due to any cause.
Time Frame
2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
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 or metastatic melanoma, who are unable to undergo complete resection, while ocular melanoma is excluded, and the overall rate of mucosal melanoma is no more than 22%. Has experienced progressed disease in previous anti-PD-1 or PD-L1 therapy for the locally advanced or metastatic melanoma (anti-PD-1 or PD-L1 therapy as neo-adjuvant or adjuvant therapy could be accepted if progressed disease occured with 6 months after the 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 previous radiotherapy administrated to the 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. Provide with tumor specimen (for testing the expression of PD -L1). Has sufficient organ and bone marrow function to meet the following laboratory examination 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) 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. Has experienced severe immunotherapy related toxicity in the previous anti-PD-1 / PD-L1 monoclonal antibody treatment, including but not limited to: Grade 3 / 4 pneumonia, 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; severe inflammatory arthritis that significantly impact the quality of patient's life; Known to has BRAF V600 mutation before signing informed consent form, and has not received any corresponding targeted therapy. With adverse reactions of previous treatment that have not recovered to CTCAE V5.0 grade ≤ 1, except for the residual hair loss effect. 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. Has active digestive ulcer, incomplete intestinal obstruction, active gastrointestinal hemorrhage or perforation. Has active interstitial pneumonia, pulmonary fibrosis, acute pulmonary disorders, et al. Has uncontrolled systemic diseases, for instance, cardiovascular and cerebrovascular disease, diabetes, hypertension, tuberculosis. 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 (CTCAE v5.0 ≥ grade 3) to any of the components in the study drug. 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. 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 the investigators.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Jun Guo, MD
Phone
010-88140650
Email
guoj307@126.com
Facility Information:
Facility Name
Beijing Cancer Hospital
City
Beijing
State/Province
Beijing
ZIP/Postal Code
100142
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jun Guo, MD
Phone
010-88140650
Email
guoj307@126.com

12. IPD Sharing Statement

Learn more about this trial

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

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