search
Back to results

Evaluate the Safety, Tolerability, and Pharmacokinetic Characteristics of HLX51 in Patients With Solid Tumor or Lymphoma

Primary Purpose

Solid Tumor, Adult Lymphoma

Status
Not yet recruiting
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
HLX51
Sponsored by
Shanghai Henlius Biotech
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Solid Tumor, Adult Lymphoma focused on measuring OX40

Eligibility Criteria

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

Inclusion Criteria: Have a full understanding of the study content, process, and possible adverse reactions before the study, and sign the informed consent form (ICF). voluntarily participate in the study. be able to complete the study as per protocol requirements. Aged ≥ 18 years at the time of signing the ICF. Patients with histologically or cytologically confirmed advanced malignant solid tumor or lymphoma, who have failed or cannot receive the standard treatment. With at least one measurable lesion according to RECIST V1.1 (for solid tumors) or the Lugano criteria (for lymphomas). Eastern Cooperative Oncology Group (ECOG) performance status score of ≤ 1 at enrollment. Expected survival > 3 months. Have appropriate hematological functions: no blood transfusion or colony stimulating factor therapy (G-CSF) within 14 days before the first administration. absolute neutrophil count ≥ 1500/μL. haemoglobin ≥ 9 g/dL. platelet count ≥ 90,000/μL. Have appropriate coagulation functions: activated partial thromboplastin time (APTT) ≤ 1.5 × ULN. prothrombin time (PT) ≤ 1.5 × ULN. international normalized ratio (INR) ≤ 1.5 × ULN. Have appropriate liver functions: total bilirubin level ≤ 1.5 × ULN, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels ≤ 2.5 × ULN (AST and ALT ≤ 5 × ULN for patients with known liver metastasis or primary hepatocellular carcinoma). Have appropriate renal functions: blood creatinine ≤ 1.5 × ULN or creatinine clearance ≥ 50 mL/min (calculated by Cockcroft-Gault formula). The first administration of the investigational product must be: at least 28 days apart from the previous major surgery, medical device treatment, or local radiotherapy. at least 28 days apart from the previous cytotoxic chemotherapy, immunotherapy, and biological agent therapy. at least 14 days apart from the previous hormone therapy and surgical operation. at least 21 days or 5 half-lives apart from the administration of small molecule targeted drugs, whichever is longer. at least 14 days apart from the traditional Chinese medicine for tumor indications. For patients with hepatocellular carcinoma, Child-Pugh score has to be A. Male and female subjects with child-bearing potential must agree to use at least one highly effective contraception method during the study and within at least 6 months after the last administration of the investigational product. Exclusion Criteria: Previous exposure to any anti-OX40 antibody or any drug targeting T-cell costimulatory signaling pathway. The adverse reactions (except alopecia and other adverse reactions determined by the investigator to have no safety risk) of previous anti-tumor therapy have not yet recovered to ≤ grade 1 (CTCAE V5.0). Those who are known to have severe anaphylaxis to macromolecular protein preparations/monoclonal antibodies or to any component of the investigational product. Patients with any of the following unstable or poorly controlled diseases: 1) Active systemic infectious diseases requiring intravenous antibiotics within 2 weeks before the first administration of the investigational product. 2) Any poorly-controlled cardiovascular and cerebrovascular clinical symptoms or diseases, including but not limited to: (1) NYHA Class II or greater cardiac failure or left ventricular ejection fraction (LVEF) < 50%. (2) unstable angina pectoris. (3) myocardial infarction and cerebral infarction within 6 months, (4) clinically significant supraventricular or ventricular arrhythmia without clinical intervention or poorly controlled after clinical intervention. 3) Other chronic diseases which, in the opinion of the investigator, may compromise the safety of the patient or the integrity of the study. 5. Assessed as unsuitable for inclusion by the investigator, due to brain metastases, spinal cord compression, or cancerous meningitis with clinical symptoms, or uncontrolled brain or spinal cord metastases that have been evidenced. 6. Previous grade 3 or greater irAEs in immunotherapy. 7. Have had other malignant tumors within 5 years before enrollment, except: (a) those with cured cervical carcinoma in situ or non-melanoma skin cancer. (b) those with cured second primary cancer without recurrence within 5 years. (c) those with double primary cancers believed to be able to benefit from this study. (d) those whose metastasis has been clearly excluded from a certain primary tumor source. 8. Have active autoimmune diseases (including but not limited to the following diseases or syndromes, such as interstitial pneumonia, colitis, hepatitis, hypophysitis, vasculitis, nephritis, hyperthyroidism, and hypothyroidism), except: vitiligo or cured childhood asthma/allergy that does not need any intervention in adulthood, autoimmune mediated hypothyroidism treated with stable dose of thyroid replacement hormone, and type I diabetes treated with stable dose of insulin. those in a stable condition and requiring no systemic immunosuppressant therapy (including corticosteroid hormone) are allowed to be enrolled. 9. Have received systemic corticosteroids (prednisone > 10 mg/d or equivalent dose of similar drug) or other immunosuppressants within 14 days before the first administration. Except: patients treated with topical, ocular, intra-articular, intranasal, and inhaled corticosteroids. those with short term use of corticosteroids for prophylaxis, such as contrast agents. 10. Patients in pregnancy [confirmed by serum beta-human chorionic gonadotropin (ß-HCG) test] or breastfeeding. 11. With a history of immunodeficiency, including human immunodeficiency virus (HIV)-positive or other acquired or congenital immunodeficiencies, or a history of organ transplantation. 12. With a history of interstitial lung disease or active tuberculosis. 13. Patients with active HBV or HCV infection (HBV DNA ≥ 104 copies/mL or positive HCV RNA). 14. Have received live vaccines within 30 days prior to the first administration. Patients whose medical history or any other evidence suggests that participation in the study may confuse the results, or subjects for whom the investigator believes the study is not in their best interest.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm Type

    Experimental

    Arm Label

    HLX51 Group

    Arm Description

    The initial dose of HLX51 is 0.3mg/kg, and 5 dose levels are designed: 0.3 mg/kg, 1 mg/kg , 2.5mg/kg, 5mg/kg, and 10mg/kg (Q3W). Patients with good tolerability and well controlled disease will receive the treatment until progressive disease (PD) without any clinical benefit, initiation of other anti-tumor therapies, death, intolerable toxicity, or withdraw the informed consent (whichever occurs first).

    Outcomes

    Primary Outcome Measures

    The Dose-Limiting Toxicity (DLT) of HLX51 within 3 weeks after the first Administration
    DLT refers to the AEs that are determined to be related to the investigational product by the investigator, whose severity will affect the escalation of dose level. In this study, the DLT observation period lasts for 3 weeks after the first administration of HLX51
    The maximum tolerated dose (MTD) of HLX51 within 3 weeks after the first administration
    MTD refers to the highest dose at which less than 1/3 of subjects in the same dose group develop DLT in cycle 1 of the dose escalation stage.

    Secondary Outcome Measures

    Full Information

    First Posted
    March 3, 2023
    Last Updated
    August 7, 2023
    Sponsor
    Shanghai Henlius Biotech
    search

    1. Study Identification

    Unique Protocol Identification Number
    NCT05788107
    Brief Title
    Evaluate the Safety, Tolerability, and Pharmacokinetic Characteristics of HLX51 in Patients With Solid Tumor or Lymphoma
    Official Title
    A Phase I Clinical Study to Evaluate the Safety, Tolerability, and Pharmacokinetic Characteristics of HLX51 (Anti-OX40 Monoclonal Antibody) in Patients With Advanced/Metastatic Solid Tumor or Lymphoma
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    March 2023
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    June 2024 (Anticipated)
    Primary Completion Date
    May 2025 (Anticipated)
    Study Completion Date
    October 2026 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Shanghai Henlius Biotech

    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
    This study is a first-in-class open-label phase I human clinical study to evaluate the safety and tolerability of HLX51 with escalated doses in the treatment of patients with advanced/metastatic solid tumors or lymphomas.
    Detailed Description
    This study is the first-in-class open-label phase I human clinical study to evaluate the safety and tolerability of HLX51 with escalated doses in the treatment of patients with advanced/metastatic solid tumors or lymphomas. In this study, 3 + 3 dose escalation method will be adopted, and the patients will be given different doses of HLX51 intravenously. Observation period of DLT lasts for 3 weeks after the first administration of HLX51.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Solid Tumor, Adult Lymphoma
    Keywords
    OX40

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 1
    Interventional Study Model
    Single Group Assignment
    Masking
    None (Open Label)
    Allocation
    N/A
    Enrollment
    30 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    HLX51 Group
    Arm Type
    Experimental
    Arm Description
    The initial dose of HLX51 is 0.3mg/kg, and 5 dose levels are designed: 0.3 mg/kg, 1 mg/kg , 2.5mg/kg, 5mg/kg, and 10mg/kg (Q3W). Patients with good tolerability and well controlled disease will receive the treatment until progressive disease (PD) without any clinical benefit, initiation of other anti-tumor therapies, death, intolerable toxicity, or withdraw the informed consent (whichever occurs first).
    Intervention Type
    Drug
    Intervention Name(s)
    HLX51
    Other Intervention Name(s)
    anti-OX40 monoclonal antibody
    Intervention Description
    anti-OX40 tetravalent agonistic humanized monoclonal antibody
    Primary Outcome Measure Information:
    Title
    The Dose-Limiting Toxicity (DLT) of HLX51 within 3 weeks after the first Administration
    Description
    DLT refers to the AEs that are determined to be related to the investigational product by the investigator, whose severity will affect the escalation of dose level. In this study, the DLT observation period lasts for 3 weeks after the first administration of HLX51
    Time Frame
    At the end of Cycle 1 (each cycle is 21 days)
    Title
    The maximum tolerated dose (MTD) of HLX51 within 3 weeks after the first administration
    Description
    MTD refers to the highest dose at which less than 1/3 of subjects in the same dose group develop DLT in cycle 1 of the dose escalation stage.
    Time Frame
    At the end of Cycle 1 (each cycle is 21 days)

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Have a full understanding of the study content, process, and possible adverse reactions before the study, and sign the informed consent form (ICF). voluntarily participate in the study. be able to complete the study as per protocol requirements. Aged ≥ 18 years at the time of signing the ICF. Patients with histologically or cytologically confirmed advanced malignant solid tumor or lymphoma, who have failed or cannot receive the standard treatment. With at least one measurable lesion according to RECIST V1.1 (for solid tumors) or the Lugano criteria (for lymphomas). Eastern Cooperative Oncology Group (ECOG) performance status score of ≤ 1 at enrollment. Expected survival > 3 months. Have appropriate hematological functions: no blood transfusion or colony stimulating factor therapy (G-CSF) within 14 days before the first administration. absolute neutrophil count ≥ 1500/μL. haemoglobin ≥ 9 g/dL. platelet count ≥ 90,000/μL. Have appropriate coagulation functions: activated partial thromboplastin time (APTT) ≤ 1.5 × ULN. prothrombin time (PT) ≤ 1.5 × ULN. international normalized ratio (INR) ≤ 1.5 × ULN. Have appropriate liver functions: total bilirubin level ≤ 1.5 × ULN, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels ≤ 2.5 × ULN (AST and ALT ≤ 5 × ULN for patients with known liver metastasis or primary hepatocellular carcinoma). Have appropriate renal functions: blood creatinine ≤ 1.5 × ULN or creatinine clearance ≥ 50 mL/min (calculated by Cockcroft-Gault formula). The first administration of the investigational product must be: at least 28 days apart from the previous major surgery, medical device treatment, or local radiotherapy. at least 28 days apart from the previous cytotoxic chemotherapy, immunotherapy, and biological agent therapy. at least 14 days apart from the previous hormone therapy and surgical operation. at least 21 days or 5 half-lives apart from the administration of small molecule targeted drugs, whichever is longer. at least 14 days apart from the traditional Chinese medicine for tumor indications. For patients with hepatocellular carcinoma, Child-Pugh score has to be A. Male and female subjects with child-bearing potential must agree to use at least one highly effective contraception method during the study and within at least 6 months after the last administration of the investigational product. Exclusion Criteria: Previous exposure to any anti-OX40 antibody or any drug targeting T-cell costimulatory signaling pathway. The adverse reactions (except alopecia and other adverse reactions determined by the investigator to have no safety risk) of previous anti-tumor therapy have not yet recovered to ≤ grade 1 (CTCAE V5.0). Those who are known to have severe anaphylaxis to macromolecular protein preparations/monoclonal antibodies or to any component of the investigational product. Patients with any of the following unstable or poorly controlled diseases: 1) Active systemic infectious diseases requiring intravenous antibiotics within 2 weeks before the first administration of the investigational product. 2) Any poorly-controlled cardiovascular and cerebrovascular clinical symptoms or diseases, including but not limited to: (1) NYHA Class II or greater cardiac failure or left ventricular ejection fraction (LVEF) < 50%. (2) unstable angina pectoris. (3) myocardial infarction and cerebral infarction within 6 months, (4) clinically significant supraventricular or ventricular arrhythmia without clinical intervention or poorly controlled after clinical intervention. 3) Other chronic diseases which, in the opinion of the investigator, may compromise the safety of the patient or the integrity of the study. 5. Assessed as unsuitable for inclusion by the investigator, due to brain metastases, spinal cord compression, or cancerous meningitis with clinical symptoms, or uncontrolled brain or spinal cord metastases that have been evidenced. 6. Previous grade 3 or greater irAEs in immunotherapy. 7. Have had other malignant tumors within 5 years before enrollment, except: (a) those with cured cervical carcinoma in situ or non-melanoma skin cancer. (b) those with cured second primary cancer without recurrence within 5 years. (c) those with double primary cancers believed to be able to benefit from this study. (d) those whose metastasis has been clearly excluded from a certain primary tumor source. 8. Have active autoimmune diseases (including but not limited to the following diseases or syndromes, such as interstitial pneumonia, colitis, hepatitis, hypophysitis, vasculitis, nephritis, hyperthyroidism, and hypothyroidism), except: vitiligo or cured childhood asthma/allergy that does not need any intervention in adulthood, autoimmune mediated hypothyroidism treated with stable dose of thyroid replacement hormone, and type I diabetes treated with stable dose of insulin. those in a stable condition and requiring no systemic immunosuppressant therapy (including corticosteroid hormone) are allowed to be enrolled. 9. Have received systemic corticosteroids (prednisone > 10 mg/d or equivalent dose of similar drug) or other immunosuppressants within 14 days before the first administration. Except: patients treated with topical, ocular, intra-articular, intranasal, and inhaled corticosteroids. those with short term use of corticosteroids for prophylaxis, such as contrast agents. 10. Patients in pregnancy [confirmed by serum beta-human chorionic gonadotropin (ß-HCG) test] or breastfeeding. 11. With a history of immunodeficiency, including human immunodeficiency virus (HIV)-positive or other acquired or congenital immunodeficiencies, or a history of organ transplantation. 12. With a history of interstitial lung disease or active tuberculosis. 13. Patients with active HBV or HCV infection (HBV DNA ≥ 104 copies/mL or positive HCV RNA). 14. Have received live vaccines within 30 days prior to the first administration. Patients whose medical history or any other evidence suggests that participation in the study may confuse the results, or subjects for whom the investigator believes the study is not in their best interest.

    12. IPD Sharing Statement

    Learn more about this trial

    Evaluate the Safety, Tolerability, and Pharmacokinetic Characteristics of HLX51 in Patients With Solid Tumor or Lymphoma

    We'll reach out to this number within 24 hrs