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About
This study is a multi-center, open, single-arm phase I/II clinical study to evaluate the recombinant humanized anti-CD47/PD-1 bifunctional antibody HX009 injection in Chinese patients with relapsed/refractory lymphoma .
Full description
Phase Ib/II efficacy exploration and confirmation phase:
Four cohorts will be conducted in parallel to initially evaluate the recombinant humanized anti-CD47/PD-1 bifunctional anti HX009 injection.
The four cohorts in the efficacy exploration phase are:
Cohort 1: Relapsed/refractory diffuse large B-cell lymphoma; Cohort 2: relapsed/refractory peripheral T-cell lymphoma (except angioimmunoblastic T-cell lymphoma).
(except angioimmunoblastic T-cell lymphoma); Cohort 3: relapsed/refractory follicular lymphoma and relapsed/refractory marginal zone lymphoma; Cohort 4: relapsed/refractory EBV-positive non-Hodgkin's lymphoma. The study will refer to the "Guidelines for Data Monitoring Committees in Drug Clinical Trials (Trial)".
A data monitoring committee will be set up to provide continuous safety monitoring of the study and to provide advice on the dosage and dosing cycle, as well as on the follow-up of the study.
The committee will provide advice on the dosage and cycle of administration, as well as on the decision-making for subsequent extension studies.
Based on the safety data from this study at the 15 mg/kg dose level, during the efficacy exploration phase, the Each cohort will enroll 10-20 subjects, for a total of 4 cohorts, and each cohort will explore 1-2 dose levels, i.e., 10 mg/kg and 15 mg/kg, with an expected enrollment of 40-80 cases. The 10 mg/kg dose level will be enrolled first.
dose level first, and after discussion between the sponsor and the DMC, 15 mg/kg dose level will be enrolled if necessary.
The dose level of 15 mg/kg will be enrolled if necessary after discussion between the sponsor and the DMC. Based on the DMC analysis, the no-trend cohort will be enrolled in a maximum of 10 cases (with the possibility of stop enrollment midway).
The Phase II efficacy confirmation phase will select 1-2 cohorts from the 4 cohorts in the efficacy exploration phase of the study with better safety and efficacy.
1-2 indications with better efficacy to further confirm the efficacy and safety of HX009 injection. Based on the safety and efficacy data from Phase I of this study, the number of cases of subjects in the efficacy confirmation phase will be re-estimated based on statistical principles.
The number of cases of subjects in the validation phase will be re-estimated based on statistical
Enrollment
Sex
Ages
Volunteers
Inclusion and exclusion criteria
Inclusion criteria：
Voluntarily participating in a clinical research study, being fully aware of and informed about the study and signing the Informed Consent Form (ICF).
Willing to follow and capable of completing all study procedures;
Male and Female. Age 18-65 years (including borderline values) in the dose-escalation phase; age 18-70 years (including borderline values) in the efficacy exploration and confirmation phase;
lymphoma diagnosed according to the 5th edition of the WHO Classification Criteria for 2022 and meeting the following definition of relapsed or refractory.
The Phase Ib efficacy exploration phase will carry out cohort expansion according to the following tumors:
an Eastern Cooperative Oncology Group (ECOG) Physical Strength Score of 0 to 2 within 14 days prior to first dose;
expected survival ≥ 3 months;
good major organ function, i.e., meeting the following criteria:
Blood system
Liver function
Renal function
Coagulation
Cardiac function
If previous antitumor therapy has been received, the following conditions need to be met:
At least one measurable lesion according to Lugano criteria within 4 weeks prior to first dose; measurable Lesions: longest diameter of lymph node >15 mm, invasive lesions elsewhere >10 mm; previously treated lesions with localized therapy such as radiotherapy, if disease progression has been demonstrated and measurable lesions are met. Measurable lesions: longest diameter of lymph node >15 mm, other invasive lesions >10 mm; lesions previously treated with localized therapy, such as radiotherapy, are considered measurable if they have been shown to be progressive and meet the definition of measurable lesions.
Female subjects must have a negative serum pregnancy test within 1 week prior to the first dose of study drug; female subjects or male subjects with a partner of childbearing potential agree to use effective contraception (e.g., oral contraceptives, intrauterine devices) for a minimum of 12 months from the time of signing the informed consent form until the last dose of study drug.
Exclusion criteria：
Prior history of a malignancy other than skin cancer or carcinoma in situ that is not melanoma (e.g., cervical cancer, bladder cancer, breast cancer, etc.) unless disease-free status has been achieved for 3 years;
failure to recover from adverse effects of prior therapy to a CTCAE 5.0 grade score of ≤1, except for residual 3. active gastrointestinal ulcers
active peptic ulcer, incomplete intestinal obstruction, active gastrointestinal bleeding and perforation;
known history of hereditary or acquired hemolytic or bleeding disorders;
subjects with primary or secondary central nervous system (CNS) lymphoma;
patients who have received prior targeted therapy with CD47 (including monoclonal antibodies, bispecific antibodies, etc.);
patients who have received a blood transfusion or hematopoietic stimulating factor therapy, such as colony-stimulating factor, erythropoietin, erythropoietin, or other stimulating factors within 2 weeks prior to the start of treatment Erythropoietin, thrombopoietin, thrombopoietin, etc;
Subjects with an active, or history of, autoimmune disease that is likely to recur or is being treated (e.g., systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, autoimmune thyroid disease, multiple sclerosis, vasculitis, glomerulonephritis, etc.), or those at high risk (e.g., who have received organ transplants and need to be treated for immune-suppressant therapy); however, enrollment is permitted in subjects who have :
major surgery during the Screening Period 28 days prior to the first dose or minor surgery within 2 weeks (except diagnostic surgery), and any elective major surgery during the planned study period;
Subjects requiring systemic corticosteroids (dose equivalent to >10 mg prednisone/day) or other immunosuppressive medications within 14 days prior to the first dose or during the study period; the following conditions to >10 mg prednisone/day) or other immunosuppressive medications within 14 days prior to the first dose or during the study period; the following were Enrollment is permitted:
Currently suffers from a serious lung disease requiring treatment or from a previous serious lung disease, interstitial lung disease, interstitial pneumonia. interstitial lung disease, interstitial pneumonia, pulmonary fibrosis, radiation pneumonitis requiring hormone therapy, etc;
uncontrolled systemic diseases such as cardiovascular diseases (severe arrhythmia, unstable angina or myocardial infarction within 6 months, etc.) Uncontrolled systemic diseases, such as cardiovascular diseases (severe arrhythmia, unstable angina or myocardial infarction within 6 months), diabetes mellitus, hypertension, etc. 13;
arterial or venous thrombosis or embolic events within 3 months prior to the first dose, such as cerebrovascular accident (including transient ischemic attack), deep vein thrombosis or pulmonary embolism;
being positive for human immunodeficiency virus or having other acquired, congenital immunodeficiency diseases. History of organ transplantation or allogeneic stem cell transplantation;
active tuberculosis disease or latent tuberculosis infection;
Subjects with active hepatitis B or hepatitis C. Hepatitis B patients: HBsAg or HBcAg positive. Except for the following:
subjects with severe active infection within 2 weeks prior to the first dose of study drug;
subjects with a known history of severe allergic reactions to large protein preparations or to any of the components of the test drug (CTC); or 18. a known subject with a previous severe allergic reaction (CTCAE 5.0 ≥ 3) to a large protein preparation or to any of the components of the test drug;
participation in a clinical trial of another drug within 4 weeks prior to the first dose;
alcohol dependence or a history of drug or substance abuse within the last 1 year
previous history of definite neurological or psychiatric disorders, such as epilepsy, dementia, poor adherence;
women who are pregnant or breastfeeding;
Subjects who have received any live or attenuated vaccine within 28 days prior to the first dose of study drug. If enrolled, subjects must not receive any live or attenuated vaccine during the study period or within 180 days of the last dose of HX009. Live Vaccines. Subjects vaccinated with inactivated, mRNA, viral vector, and labeled protein COVID-19 vaccines are eligible to participate in the study. Subjects vaccinated with inactivated, mRNA, viral vector and labeled protein COVID-19 vaccines are eligible to participate in the study and the vaccination timeline should follow local guidelines;
subjects who, in the opinion of the Investigator, are otherwise unsuitable for participation in this trial.
Primary purpose
Allocation
Interventional model
Masking
99 participants in 1 patient group
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Central trial contact
shuai wang
Data sourced from clinicaltrials.gov
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