Trial Title:
A Clinical Study of Injectable IMM0306 in Combination With Lenalidomide
NCT ID:
NCT05771883
Condition:
B-cell Non-Hodgkin's Lymphoma
Conditions: Official terms:
Lymphoma
Lymphoma, Non-Hodgkin
Lymphoma, B-Cell
Lenalidomide
Conditions: Keywords:
0306-03
Study type:
Interventional
Study phase:
Phase 1/Phase 2
Overall status:
Not yet recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
IMM0306
Description:
IMM0306 is a fusion protein of CD20 mAb with the CD47 binding domain of SIRPα. The Fc
segment of the recombinant protein in IMM0306 is IgG1 and has been modified by
ADCC-enhanced genetic engineering.
Arm group label:
DLBCL and other B-NHL patients such as FL, MZL, MCL, etc.
Other name:
IMM0306 Ingection
Intervention type:
Drug
Intervention name:
Lenalidomide capsule
Description:
Chemical name 3-(7-amino-3-oxo-1H-isoindol-2-yl)piperidin-2,6-dione, molecular formula C
13H 13 N 3 O 3, is an anti-tumor drug developed by Celgene Biopharmaceutical Company in
the United States, with multiple effects such as anti-tumor, immunomodulatory and
anti-angiogenesis
Arm group label:
DLBCL and other B-NHL patients such as FL, MZL, MCL, etc.
Other name:
Revlimid
Summary:
The objective of this study was to evaluate the safety and efficacy of IMM0306 in
combination with lenalidomide in patients with relapsed/refractory CD20-positive B-cell
non-Hodgkin lymphoma.
Detailed description:
Main study purpose:
To assess the safety and tolerability of IMM0306 in combination with lenalidomide to
determine the maximum tolerated dose (MTD) (if available) and the recommended Phase 2
dose (RP2D).
Secondary study purpose
1. To assess the antitumor efficacy of IMM0306 in combination with lenalidomide.
2. To assess the immunogenicity of IMM0306 in combination with lenalidomide.
3. To evaluate the pharmacokinetic (PK) profile of IMM0306 in combination with
lenalidomide.
Exploratory study purpose:
1. Explore the correlation between exposure to IMM0306 and efficacy and safety (data
permitting).
2. Explore the correlation of biomarkers with safety.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- 1)Patients should voluntarily sign the informed consent form, understand the study
and be willing to follow the protocol and willing to complete all study procedures;
- 2)Male or female, aged ≥ 18 years old;
- 3)Phase Ib: CD20-positive B-cell non-Hodgkin lymphoma (B-NHL) diagnosed by
histopathology which meets the criteria of 2016 WHO classification of lymphoid
neoplasms, including but not limited to diffuse large B-cell lymphoma (DLBCL),
follicular lymphoma (FL), mantle cell lymphoma (MCL), marginal zone B-cell lymphoma
(MZL), etc. Among them, indolent B-NHL must have failed at least 1 line of standard
regimen, and aggressive B-NHL must have failed 2 or more lines of standard regimen.
At least one regimen containing anti-CD20 monoclonal antibody monotherapy or in
combination;
Phase IIa: CD20-positive B-cell non-Hodgkin lymphoma (B-NHL) of the following subtypes
diagnosed by histopathology which meets the criteria of 2016 WHO classification of
lymphoid neoplasms:
Cohort 1 Indications：Relapsed/refractory follicular lymphoma (FL, Grade 1-3a), 2 L；
Inclusion Criteria：1）Histopathologically diagnosed CD20-positive FL Failure after first
line treatment with regimens containing anti-CD20 monoclonal antibody monotherapy or in
combination； Cohort 2 Indications：Relapsed/refractory marginal zone lymphoma (MZL), 2L
Classification of MZL:
- Splenic MZL
- Lymph node MZL Extramodal (MALT) Inclusion Criteria：1）Histopathologically diagnosed
CD20-positive MZL Failure after first line treatment with regimens containing
anti-CD20 monoclonal antibody monotherapy or in combination Cohort 3
Indications：Relapsed/refractory diffuse large B-cell lymphoma (DLBCL), 2 L Note:
Including DLBCL transformed by follicular lymphoma Inclusion
Criteria：1）Histopathologically diagnosed CD20-positive DLBCL Failure after first
line treatment with regimens containing anti-CD20 monoclonal antibody monotherapy or
in combination Note: Relapse is defined as disease progression after response (CR or
PR) with adequate treatment, and at least one regimen containing anti-CD20;
refractory is defined as failure to achieve a response after adequate treatment with
regimen containing anti-CD20, or disease progression (PD or SD) during
treatment/within 6 months after completion of adequate treatment.
Based on the safety and efficacy data from the Phase Ib study, the indications in the
Phase IIa study may be adjusted, including the addition of new indications requiring
determination of efficacy (eg, including but not limited to Waldenström's
macroglobulinemia/lymphoplasmacytic lymphoma) or the deletion of indications (eg,
including but not limited to DLBCL).
- 4)At least one measurable tumor lesion. Measurable lesions (2014 Lugano lymphoma
response evaluation criteria (see details)): Longest diameter of lymph nodes > 15
mm, extranodal lesions > 10 mm; lesions previously treated with local therapy such
as radiotherapy are considered measurable if disease progression has been
demonstrated;
- 5)Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2;
- 6)Expected survival of at least 3 months;
- 7)The interval between the previous anti-tumor therapy and the first dose of this
study must meet the following conditions: Prior anti-CD20 monoclonal antibody
therapy with a discontinuation period of greater than 4 weeks; Prior CAR-T cell
therapy with a washout period of greater than 4 weeks; Patients who have previously
received chemotherapeutic drugs should discontinue for more than 4 weeks; Patients
who have previously received small molecule targeted therapy should discontinue for
more than 4 weeks; Patients who have previously received immune checkpoint
inhibitors should discontinue for more than 8 weeks; Patients who have previously
received surgery, radiotherapy and other anti-tumor drugs (including macromolecular
targeted drugs, immunomodulators, traditional Chinese medicinal products with clear
anti-tumor effect and indications of non-Hodgkin lymphoma, etc.) should have a
interval of greater than 4 weeks;
- 8)Toxicities of prior anticancer therapy have been recovered to CTCAE v5.0 Grade ≤ 1
(except for residual alopecia effects) or baseline;
- 9)Adequate organ and hematopoietic function: Absolute neutrophil count (ANC) ≥ 1.5 ×
109/L (no short-acting drugs for leucopenia within 1 week before the first dose and
no long-acting drugs for leucopenia within 3 weeks before the first dose); Platelets
≥ 90 × 109/L (the patient has not received platelet transfusion therapy and
thrombopoietin (TPO) therapy within 2 weeks before the first dose); Hemoglobin ≥ 90
g/L (patient has not received red blood cell transfusion therapy or erythropoietin
(EPO) therapy within 2 weeks prior to the first dose); Serum creatinine (formula is
shown in 附录 2) ≤ 1.5 times of upper limit of normal (ULN) or endogenous creatinine
clearance (CCr) ≥ 50 mL/min; for subjects with urine protein ≥ 2 + detected by urine
dipstick at baseline, 24-hour urine protein quantitative test shall be performed,
and the result shall be < 1g; Aspartate aminotransferase (AST) and alanine
aminotransferase (ALT) ≤ 3.0 times ULN for patients without liver involvement; AST
and ALT ≤ 5.0 times ULN for patients with liver involvement; Serum total bilirubin
(TBIL) ≤ 1.5 times ULN; International normalized ratio (INR) ≤ 2 times ULN, or
activated partial thromboplastin time (APTT) ≤ 1.5 times ULN;
- 10)Female patients of childbearing potential must have a negative blood pregnancy
test within 7 days prior to the first dose; any male and female patients of
childbearing potential must agree to use an effective method of contraception
throughout the study and for 6 months after the last dose of study drug. (Details
are shown in Appendix 7)
Exclusion Criteria:
- 1)Patients with current or previous primary central nervous system lymphoma (PCNSL)
or secondary central nervous system involvement. Patients with central nervous
system symptoms must undergo lumbar puncture and magnetic resonance imaging (MRI)
for exclusion;
- 2)Patients who have received allogeneic hematopoietic stem cell transplant or other
organ transplant or received autologous hematopoietic stem cell transplant within
100 days prior to the first dose;
- 3)Patients who have received live attenuated vaccines within 4 weeks prior to the
first dose or planned during the study;
- 4)Patients with a history of malignancy within the last 5 years, except for patients
with completely cured basal cell carcinoma of skin or squamous cell carcinoma of
skin, melanoma in situ, and cervical carcinoma in situ and/or patients with any
malignancy for whom the cancer has been cured without disease or for at least 5
consecutive years without disease;
- 5)Patients with active autoimmune diseases or medical history that may relapse
(e.g., systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel
disease, autoimmune thyroid disorder, multiple sclerosis, vasculitis,
glomerulonephritis, etc.), or patients at high risk. However, the following patients
may be considered for enrollment if they have stable disease as assessed by the
investigator: Autoimmune hypothyroidism requiring only hormone replacement therapy;
Skin disease not requiring systemic treatment (e.g., eczema, rash accounting for
less than 10% of the body surface);
- 6)Patients who have undergone major surgery within 28 days prior to the first dose
or are expected to have major surgery during this study;
- 7)Subjects with deep venous embolism or pulmonary artery embolism within 6 months
prior to screening;
- 8)Subjects requiring treatment with systemic corticosteroids (> 10 mg/day prednisone
or equivalent dose) or other immunosuppressive agents within 7 days prior to the
first dose or during the study, except for topical glucocorticoids administered by
nasal spray, inhalation, or other routes, or physiological doses of systemic
glucocorticoids;
- 9)Patients who require chronic oral administration of aspirin or other non-steroidal
anti-inflammatory drugs, clopidogrel and other drugs that inhibit platelet
aggregation (except for patients who meet the inclusion criteria who can suspend the
treatment as assessed by the investigator);
- 10)Patients with current interstitial lung disease or pneumonitis, active
tuberculosis infection;
- 11)Patients with systemic diseases not stably controlled after treatment, such as
diabetes, severe organic cardiovascular and cerebrovascular diseases;
- 12)The patient's heart meets any of the following conditions: Left ventricular
ejection fraction (LVEF) ≤ 55%; Congestive heart failure or active heart disease of
New York Heart Association (NYHA) (see Appendix 3) Class II or greater; Serious
arrhythmia requiring treatment (except for atrial fibrillation and paroxysmal
supraventricular tachycardia which are judged by the investigator as having no
effect on the study); QTc interval ≥ 450 ms for males and ≥ 470 ms for females (QTc
formula is shown in Appendix 4); Have myocardial infarction or bypass or stent
surgery within 6 months before administration; Other cardiac diseases that are not
suitable for enrollment judged by the investigator;
- 13)Patients with human immunodeficiency virus (HIV) infection, hepatitis B surface
antigen (HBsAg) and/or hepatitis B core antibody (HBcAb) positive at screening, and
HBV-DNA above the lower limit of measurement; HCV antibody positive at screening and
HCV-RNA above the lower limit of measurement;
- 14)Evidence of uncontrollable serious active infection at screening (eg, sepsis,
bacteremia, fungemia, viremia, etc);
- 15)Subjects with known previous severe allergic reactions (CTCAE v5.0 grade ≥ 3) to
macromolecular protein preparations/monoclonal antibodies and any components of the
investigational product;
- 16)Subjects who have participated in other interventional drug or medical device
clinical studies or are receiving other clinical study treatments (other than
non-interventional studies) within 4 weeks prior to the first dose of this study;
- 17)Patients with a clear past history of neurological or mental disorders, such as
epilepsy, dementia, and poor compliance;
- 18)Pregnant or lactating women;
- 19)Patients with history of stroke or intracranial hemorrhage within 6 months;
- 20)Patients with active or documented haemorrhage of digestive tract within 6 months
(eg, esophageal or gastric varices, ulcer bleeding);
- 21)Patients who are ineligible for participation in this study in the opinion of the
investigator for other reasons, such as rapid disease progression at screening, etc.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Start date:
May 2023
Completion date:
November 2025
Lead sponsor:
Agency:
ImmuneOnco Biopharmaceuticals (Shanghai) Inc.
Agency class:
Other
Source:
ImmuneOnco Biopharmaceuticals (Shanghai) Inc.
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05771883
