Recombinant Humanized Anti-CD47/PD-1 Bifunctional Antibody HX009 in Patients With Relapsed/Refractory Lymphoma

• Status: Recruiting
• Trial end date: 2023-08-30
• Target enrollment: 0
• Participant gender: All

Summary

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 .

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Waterstone Hanxbio Pty Ltd
• Treatments: Antibodies; Antibodies, Bispecific

Criteria

Inclusion Criteria:

1. Volunteer to participate in clinical research, fully understand and know the research and sign the informed consent (ICF), willing to follow and have the ability to complete all research procedures.

2. Male or female,age at dose-escalation part is 18 to 65 years old; age at efficacy exploration and confirmation is 18 to70 years old .

3. Lymphoma diagnosed according to the 2017 WHO classification criteria and meets the following recurrence and refractory definition. Subjects enrolled in the group must meet the following criteria (subjects in the dose escalation part are included in the following tumor types, but not limited to the following categories; the efficacy exploration and confirmation part will be based on the following tumor types) (1)Patients with relapsed/refractory diffuse large B-cell lymphoma: need to have received at least two standard regimens of systemic treatment; (2)Relapsed/refractory peripheral T-cell lymphoma (except for angioimmunoblastic T-cell lymphoma): need to have received at least two standard regimens of systemic treatment; among them, subjects with NK/T-cell lymphoma need to be treated in the past Have been treated with pegaspase or L-asparaginase; (3)Relapsed/refractory classic Hodgkin's lymphoma: need to have received at least two standard regimens of systemic treatment, one of which includes PD-1 monoclonal antibody, and progresses in the treatment with PD-1 regimen or PD-1 persists Complete remission has not been achieved after treatment for more than 12 months; (4)Relapsed/refractory mantle cell lymphoma: requires at least two standard regimens of systemic treatment, one of which includes a BTK inhibitor; (5)Relapsed/refractory follicular lymphoma and marginal zone lymphoma; systemic treatment of at least two standard regimens is required;

4. The Eastern Cooperative Oncology Group (ECOG) stamina score of 0-2 points within 14 days before the first medication;

5. Life expectancy ≥3months

6. The main organs function well and meet the following standards :

Blood system (1)The absolute value of neutrophils (ANC) ≥1.5×10^9 /L; patients with bone marrow invasion, ANC ≥1.0×10^9 /L; (2)The subject has not received platelet transfusion within 1 week, and platelets

• 75×10^9/L (without bone marrow invasion), platelets ≥50.0×10^9/L (with bone marrow or spleen invasion); (3)The subject has not received red blood cell transfusion within 4 weeks, (4)hemoglobin (HB) ≥90g/L; with bone marrow invaded, HB≥80 g/L; liver function

1. Aspartate aminotransferase ≤2.0×ULN;

2. Alanine aminotransferase ≤2.0×ULN;

3. Total bilirubin≤1.5×ULN (except Gilbert syndrome); Kidney function

1. Serum creatinine≤1.5×ULN; Coagulation function International normalized ratio (INR) ≤ 2 times ULN, or activated partial thromboplastin time (APTT) ≤ 1.5 times ULN; 7. If you have ever received anti-tumor therapy, you need to meet the following conditions:

1. The interval between systemic radiotherapy and the first administration is ≥3 weeks, and the interval between local radiotherapy or radiotherapy for bone metastasis is ≥2 weeks;

2. Past chemotherapy, immunotherapy (CAR-T therapy, etc.), biological therapy (tumor vaccine, cytokines or growth factors that control cancer), targeted therapy, antibody-conjugated drugs, and the interval between the first administration ≥ 4 weeks or 5 half-life (whichever is longer) (the interval between the first administration of mitomycin or nitrosourea chemotherapeutics is ≥6 weeks);

3. The interval between the first administration of traditional Chinese medicine and Chinese patent medicine with obvious anti-tumor treatment was ≥1 week; 8.Within 4 weeks before the first medication, the investigator found at least one measurable or evaluable tumor lesion according to Lugano criteria; measurable lesions: the longest diameter of the lymph node is ≥15 mm, and the lesions in other parts are ≥10 mm; a lesion that has previously received local treatment such as radiotherapy is considered a measurable lesion if it has been proven that the disease has progressed and meets the definition of a measurable lesion; 9.The female subjects' serum/urine pregnancy test within 2 weeks before the first administration of the drug must be negative; female subjects or male subjects whose spouse is of childbearing age need to agree from the signing of the informed consent form to after the last administration of the study drug Use contraceptive measures (such as oral contraceptives, intrauterine contraceptives, sexual desire control or barrier contraception combined with spermicide) for at least 12 months, and do not breastfeed .

Exclusion Criteria:

1. Those suffering from other malignant tumors within 5 years before enrollment, except for cured cervical carcinoma in situ, cured basal cell carcinoma of the skin, and squamous cell carcinoma of the skin;

2. The adverse reactions of previous treatments failed to recover to CTCAE 5.0 grade score ≤1, except for residual hair loss effects;

3. Active peptic ulcer, incomplete intestinal obstruction, active gastrointestinal bleeding and perforation;

4. Known history of hereditary or acquired hemolytic or bleeding disorders;

5. Subjects with primary or secondary central nervous system (CNS) lymphoma, or symptomatic CNS injury, or spinal cord compression, or cancerous meningitis;

6. Pleural effusion, abdominal effusion or pericardial effusion with clinical symptoms;

7. Those who have received blood transfusion therapy within 4 weeks before treatment or hematopoietic stimulating factor therapy, such as colony stimulating factor, erythropoietin, thrombopoietin, etc.;

8. Active, or history of, autoimmune disease (within the past 2 years) that may recur (eg, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, autoimmune thyroid disease, multiple sclerosis, vasculitis, glomerulitis, etc) or are at high risk (eg, receiving an immunosuppressive treatment for an organ transplant); however, subjects with the following are allowed to enroll:

1. Type I diabetes that is stable after a fixed dose of insulin

2. Only requiring hormone replacement therapy for autoimmune hypothyroidism

3. Skin disease that does not require treatment such as eczema, rash that accounts for <10% of the body surface, psoriasis without ophthalmological symptoms (mainly manifested as dry eye, blepharitis, conjunctivitis, eyeball adhesion, keratitis and uveitis); 9.It is expected that there will be major surgeries during the 28 days screening period during the study period (except for diagnostic surgeries) 10.Subjects who need to receive systemic corticosteroids (dose equivalent to >10 mg prednisone/day) or other immunosuppressive drugs within 14 days before the first dose or during the study period; the following conditions are allowed to be included:

1. Subjects use topical or inhaled glucocorticoids;

2. Short-term (≤7 days) use of glucocorticoids to prevent or treat non-autoimmune allergic diseases; 11.Currently suffering from acute lung disease, interstitial lung disease, interstitial pneumonia, pulmonary fibrosis, radiation pneumonia that requires hormone therapy, etc.; 12.Uncontrolled systemic diseases after treatment, such as cardiovascular disease (unstable angina or myocardial infarction within 6 months, etc.), diabetes, hypertension, etc.; 13.Arterial or venous thrombosis or embolic events occurred within 3 months before the first administration, such as cerebrovascular accident (including transient ischemic attack), deep vein thrombosis or pulmonary embolism; 14.Human immunodeficiency virus antibody positive or suffering from other acquired or congenital immunodeficiency diseases, history of organ transplantation or allogeneic stem cell transplantation; 15.Subject with a history of tuberculosis (without complete anti-tuberculosis treatment), or active tuberculosis at the time of screening; 16.Subjects with active chronic hepatitis B or active hepatitis C. Except for hepatitis B virus carriers, stable hepatitis B after drug treatment (DNA titer not higher than 500 IU/mL or copy number <1000 copies/mL) and cured hepatitis C subjects (HCV RNA test negative); 17.Those who have had a serious infection within 4 weeks before the first administration, or have an active infection within 2 weeks before the first administration of the drug and require oral or intravenous antibiotic treatment; 18.People who are known to have had severe allergic reactions to macromolecular protein preparations/monoclonal antibodies, or to any test drug component (CTCAE 5.0 grade >3); 19.Participated in other drug clinical trials within 4 weeks before the first administration; 20.Alcohol dependent or have a history of drug abuse or drug abuse within the past year; 21.Have a clear history of neurological or mental disorders, such as epilepsy, dementia, or poor compliance; 22.Women who are pregnant or breastfeeding; 23.Those who have received the new crown vaccine within one month before the first administration; 24.The researcher believes that the subjects who are not suitable for participating in this trial due to other reasons.