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

  • STATUS
    Recruiting
  • End date
    Aug 30, 2023
  • participants needed
    99
  • sponsor
    Waterstone Hanxbio Pty Ltd
Updated on 21 March 2022

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 .

Description

The study is comprised of two parts: phase I is the dose escalation part, and phase II is the efficacy exploratory part and the efficacy confirmation part.

Phase I dose escalation part: it is planned to recruit patients with relapsed/refractory lymphoma.Four dose groups : 7.5 mg/kg, 15 mg/kg, 22.5 mg/kg and 30 mg/kg ,will be explored according to the 3+3" principle. First, 3 subjects were enrolled. If no DLT occur during the DLT observation period, the next dose group test was conducted;if DLT occurs in 2 or more of the 3 patients in this group, the climbing will be terminated or a lower dose group shall be recommended by the Safety Review Committee ; if DLT occurs in only 1 of the 3 patients, add 3 patient, if 3 patients did not develop DLT, the dose is escalated to the next group; if DLT occurs in 1 or more of the three additional patients, the dose escalation will be terminated or the Safety Review Committee recommends a new lower dose group. Safety Review Committee will be based on the safety and tolerability of every dose group and PK(pharmacokinetics) and PD (pharmacodynamics) data, for the next dose increasing amplitude and dosing cycle are discussed, at the same time also will recommend whether to increase the dose of unplanned group or dosing method and dosing cycle of exploration group.

phase II is the efficacy exploratory part and the efficacy confirmation part. : 5 cohorts will be carried out in parallel to initially evaluate the effectiveness of recombinant humanized anti-CD47/PD-1 bifunctional antibody HX009 injection.

The 5 cohorts in the efficacy exploration part are:

Cohort 1: Relapsed/refractory diffuse large B-cell lymphoma; Cohort 2: Relapsed/refractory peripheral T-cell lymphoma; Cohort 3: Relapsed/refractory classic Hodgkin's lymphoma; Cohort 4: Relapsed/refractory mantle cell lymphoma; Cohort 5: Relapsed/refractory follicular lymphoma and marginal zone lymphoma; In the efficacy exploration part, each cohort will enroll 15 subjects, a total of 5 cohorts, and 75 patients are expected to be enrolled.

According to the analysis of the Safety Review Committee , the cohort with the efficacy enters the efficacy confirmation part, and the number of subjects in the efficacy confirmation part is re-estimated according to statistics; the cohort without the efficacy trend is enrolled up to 15 patients (according to the analysis of the Safety Review Committee , the group can be stopped midway).

In the second phase of efficacy confirmation , one or two indications with better safety and efficacy among the 5 cohorts in the efficacy exploration part will be selected to further confirm the efficacy of recombinant humanized anti-CD47/PD-1 bifunctional antibody HX009 injection And safety.

Details
Condition Relapsed/Refractory Lymphoma
Treatment Recombinant humanized anti-CD47/PD-1 bifunctional antibody HX009 injection
Clinical Study IdentifierNCT05189093
SponsorWaterstone Hanxbio Pty Ltd
Last Modified on21 March 2022

Eligibility

Yes No Not Sure

Inclusion Criteria

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
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
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
The Eastern Cooperative Oncology Group (ECOG) stamina score of 0-2 points within 14 days before the first medication
Life expectancy ≥3months
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
×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
Aspartate aminotransferase ≤2.0×ULN
Alanine aminotransferase ≤2.0×ULN
Total bilirubin≤1.5×ULN (except Gilbert syndrome); Kidney function
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
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
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)
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

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
The adverse reactions of previous treatments failed to recover to CTCAE 5.0 grade
score ≤1, except for residual hair loss effects
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, or
symptomatic CNS injury, or spinal cord compression, or cancerous meningitis
Pleural effusion, abdominal effusion or pericardial effusion with clinical
symptoms
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
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
Type I diabetes that is stable after a fixed dose of insulin
Only requiring hormone replacement therapy for autoimmune hypothyroidism
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)
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
Subjects use topical or inhaled glucocorticoids
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
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
Have a clear history of neurological or mental disorders, such as epilepsy
dementia, or poor compliance; 22.Women who are pregnant or breastfeeding
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
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