Recruitment of clinical trials of IMM0306 in the treatment of refractory or recurrent CD20 positive B-cell non Hodgkin's lymphoma

1. Brief introduction of test drug

IMM0306 is a recombinant human SIRPα and anti-CD20 antibody fusion protein, which is independently developed by ImmuneOnco Biopharmaceuticals (Shanghai) Co., Ltd. IMM0306 can bind to CD20 on tumor cell membrane and kill tumor cells through ADCP, ADCC and CDC; IMM0306 can also reverse the inhibitory effect of tumor cells on macrophages by blocking the binding of CD47 of tumor cells with SIRP α of macrophages. At the same time, the fusion protein can activate macrophages through Fc receptor on the surface of cell membrane, and finally destroy tumor cells; in addition, IMM0306 can also block the binding of CD47 of tumor cells with SIRPα of macrophages The activated macrophages present tumor antigen to T cells and activate T cells to kill tumor.

IMM0306 drug advantages: another single target drug, recombinant human SIRP α-Fc fusion protein drug IMM01, was completed in April 2020, and the second dose group clinical trial study was completed in the Hematology Hospital of Chinese Academy of Medical Sciences. The low dose of IMM01 project can work and make the subjects benefit continuously.

2. Research purpose

Objective to evaluate the safety and tolerability of IMM0306 for injection in the treatment of refractory or recurrent CD20 positive B-cell non Hodgkin's lymphoma (B-NHL); Objective to determine the pharmacokinetics of IMM0306 for injection in patients with refractory or recurrent CD20 positive B-NHL.

3. Research design

This study is a clinical study of single arm, multi center, open, multi dose climbing, single combined multiple administration.

4. Research Center

Cancer Hospital of Chinese Academy of Medical Sciences, Third Hospital of Peking University and Henan cancer hospital.

5. Inclusion criteria

1) Voluntarily sign the informed consent form, understand the study, and are willing to follow and have the ability to complete all research procedures;

2) Male and female, age ≥ 18 years old, ≤ 70 years old;

3) Relapsed or refractory CD20 positive B-cell non Hodgkin's lymphoma (B-NHL) diagnosed and treated with line 2 or more, including but not limited to diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), mantle cell lymphoma (MCL), mucosa associated lymphoid tissue lymphoma (MALT-L), small lymphocyte lymphoma (SLL) / chronic lymphoblastic leukemia (c) Ll);

4) Patients receiving autologous hematopoietic stem cell transplantation (ASCT) need no remission or recurrence after ASCT; if they receive remedial treatment after ASCT, they must have no response or recurrence after the last treatment;

5) At least one tumor can be measured or evaluated;

6) The ECoG score was 0-1;

7) The expected survival time was at least 6 months;

8) It has recovered from the toxicity of previous treatment to CTCAE V5.0 grade ≤ 1 (except residual alopecia effect);

9) It has suitable organs and hematopoietic function

10) The blood pregnancy test of fertile women within 7 days before screening was negative; any fertile male and female patients must agree to use effective contraceptive methods throughout the study period and within six months after the end of the study.

6. Exclusion criteria

1) Active central nervous system (CNS) lymphoma (patients with CNS symptoms must undergo lumbar puncture and magnetic resonance imaging (MRI) to exclude CNS lymphoma);

2) Patients who have received allogeneic hematopoietic stem cell transplantation and other organ transplantation (except those who have received autologous hematopoietic stem cell transplantation for more than half a year) and who have received car-t cell therapy for less than half a year;

3) Receiving live attenuated vaccine within 4 weeks before the first dose of study treatment or planned during the study period;

4) Previous or present malignancies;

5) Patients with active autoimmune diseases or with a history of recurrence (such as systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, autoimmune thyroid disease, multiple sclerosis, vasculitis, glomerulonephritis, etc.) or high-risk patients. However, patients with the following diseases were allowed to enter the group:

Patients with autoimmune hypothyroidism who only need hormone replacement therapy;

Skin diseases that do not require systemic treatment (e.g. eczema, skin rashes less than 10% of the body surface);

6) Patients who had undergone major surgery within 28 days before enrollment or expected major surgery during the study period;

7) Subjects requiring systemic corticosteroids (> 10 mg / day prednisone or equivalent) or other immunosuppressive drugs within 7 days prior to the first dose of study treatment or during the study period, excluding nasal, inhaled or other local glucocorticoids or physiological doses of systemic glucocorticoids;

8) Long term anticoagulant therapy is needed

9) He is suffering from acute lung disease, interstitial lung disease or pneumonia (except for local interstitial pneumonia induced by radiotherapy), pulmonary fibrosis, etc;

10) Systemic diseases that are not stably controlled after treatment, such as diabetes mellitus and severe organic cardiovascular and cerebrovascular diseases;

11) The patient's heart meets any of the following conditions:

Left ventricular ejection fraction (LVEF) ≤ 55%;

New York Heart Association (NYHA) grade II and above congestive heart failure or active heart disease;

Serious arrhythmias that need treatment (except atrial fibrillation and paroxysmal supraventricular tachycardia which have no effect on the test as judged by the researcher);

QTc interval ≥ 450ms in males and 470ms in females (qtcb = QT / rr1 / 2);

There were myocardial infarction, bypass grafting and stent operation within 6 months before administration;

Other heart diseases which were judged by researchers as unsuitable to be included in the study;

12) Patients with HIV infection, hepatitis B surface antigen (HBsAg) positive or (and) HBV-DNA higher than the lower limit of measurable, HCV antibody positive or (and) HCV-RNA higher than the lower measurable limit in the screening period;

13) There was evidence of uncontrollable severe active infection (such as sepsis, bacteremia, mycoemia, viremia, etc.) during screening;

14) Patients with known severe allergic reactions to macromolecular protein preparations/monoclonal antibodies and any components of the test drug (CTCAE V5.0 grade is greater than grade 3);

15) In this study, we participated in clinical trials of other drugs or medical devices within 4 weeks before the first administration of drugs, or less than 5 half lives of other research drugs before the first administration,;

16) Have a history of alcohol or drug abuse in the past one year;

17) Patients with a clear history of neurological or mental disorders, such as epilepsy, dementia, and poor compliance;

18) Pregnant or lactating women;

19) The patients who were considered unsuitable for the study due to other reasons were considered by the researchers

7. Contact us

If you meet the requirements of study subjects or are interested in the details of the study drug, please contact us. Clinical research department of ImmuneOnco Biopharmaceuticals (Shanghai) Co., Ltd., Contact person: Ma Huizi, Tel: (021) 58356573-815; 15617814868.