CD20 positive and/or CD19 positive B cell non-Hodgkin's lymphoma
Conditions
Interventions
treatment group:Intravenous injection of 1A46
Sponsors
Beijing Cancer Hospital
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: 1. Male or female patients aged 18 years or older; 2. Be able to sign informed consent form voluntarily and understand the study, including the purpose and the procedure and be able to comply with protocol requirements; 3. Patient populations: Dose Escalation: a. Aggressive NHL (aNHL) : MCL, each subtype of DLBCL and FL3b, PMBCL, high level of B cell lymphoma, etc. b. Indolent NHL (iNHL) : including FL1-3 a grade, MZL, small lymphocytic lymphoma, etc. c. all NHL patients should must: relapsed after or failed to respond to at least two prior systemic treatment regimens, including at least one containing an anti-CD20-directed therapy,received or be ineligible for autologous SCT, , there is no other standard treatment is thought to have clinical benefit Dose Expansion: Cohort 1: FL patients who are refractory to or relapsed after = 2 prior regimens and have no other standard of care with clinical benefit. Cohort 2: r/r DLBCL patients who have progressed after or refractory to 2 or more lines of systemic therapy and have not received prior therapy with CAR-T, and do not have standard treatment with clinical benefit. Cohort 3: r/r DLBCL patients who have progressed after or refractory to 2 or more regimens which consisted of a CAR-T therapy that has been approved by a health authority, do not have standard treatment with clinical benefit. 4. NHL patients must have expression of CD20 and/or CD19-expression as determined by immunohistochemistry (IHC) at a certified laboratory within 6 months before study entry without intervening treatment of NHL, otherwise a fresh biopsy must be obtained to determine if CD19 and/or CD20 continue to be expressed by tumor cells. 5. = 1 measurable target lesion as defined by Lugano 2014 criteria (= 15 mm in its largest dimension for nodal lesions or= 10 mm in its largest dimension for extranodal lesion). 6. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1; Life expectancy> 3 months. 7. Subjects with fertility must take effective contraceptive measures after signing the ICF until at least 12 months after the last administration of 1A46. 8. Clinical laboratory values as specified below during the screening period. ? Total bilirubin must be 50 mL/min (the Cockcroft-Gault formula). ? Hemoglobin (Hb) must be = 80 g/L. No transfusion of red blood cells or use of hematopoietic stimulating factors such as TPO within 14 days before the study. ? Neutrophil count must be >1.0×109/L, No granulocyte or granulocyte macrophage colony-stimulating factor and other hematopoietic stimulating factors were used within 14 days before the study. ? Platelet count must be >75×109/L, No platelet transfusion or use of hematopoietic stimulating factors such as TPO and IL-11 within 14 days prior to testing. ? Prothrombin time-international normalized ratio (PT-INR) must be = 1.5. Patients who are appropriately anticoagulated for a preexisting medical condition [e.g., atrial fibrillation] may be eligible with documented and evaluated by investigators and sponsor approval. 9. R
Exclusion criteria
Exclusion criteria: 1. Patient has brain metastasis or other significant neurological conditions. 2. Female patients who are lactating and breastfeeding or have a positive serum pregnancy test during the screening period, or intending to become pregnant during the study. 3. At the time of enrollment, there are active infections, including bacteria, viruses (including EB virus, cytomegalovirus, etc.), fungi, mycobacteria, parasites, or other infections (excluding nail bed fungal infections), or there are any serious infections that require antibiotic intravenous injection treatment or hospitalization treatment (relating to the completion of the course of antibiotics) within the first 4 weeks prior to enrollment. 4. Treatment with corticosteroids (> 10 mg daily prednisone or equivalent) or immunosuppressive medication( including but not limited to cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor drugs) = 7 days before the first dose of 1A46, with the following exceptions: local, ocular, intra-articular, nasal, or inhaled corticosteroids, and those who receive corticosteroid replacement therapy due to adrenal insufficiency. 5. Treatment with any investigational products (including cell or gene therapy) within 5 half-lives of the agent or 4 weeks prior to the first dose of 1A46, whichever is shorter. 6. Received Systemic anticancer therapy (including I/O therapies) within 5 half-lives of the agent or 4 weeks prior to the first dose of 1A46, whichever is shorter. 7. Treatment with radiotherapy within 2 weeks before the study entry. If the patients have received radiotherapy within 4 weeks before enrollment, there must be at least one measurable lesion outside the radiotherapy area, or if the patient only has measurable lesion progression after radiotherapy, they can be enrolled. 8. Treatment with CAR-T within 30 days before the study entry. 9. Treatment with autologous stem cell transplantation therapy within 100 days before the study entry. 10. Prior allogeneic hematopoietic stem cell transplantation. 11. Prior solid organ transplantation. 12. Positive human immunodeficiency virus (HIV) antibodies; positive EB virus nucleic acid; positive Cytomegalovirus nucleic acid positive; Hepatitis C virus (HCV) antibody is positive, and the result of HCV RNA detection is positive; Hepatitis B surface antigen [HBsAg] is positive, and hepatitis B virus DNA test result is positive or greater than the upper limit of normal value. 13. Admission or evidence of illicit drug use, drug abuse, or alcohol abuse. 14. Have ischemic or hemorrhagic cerebrovascular disease, epilepsy, dementia, or = grade 3 gastrointestinal bleeding within the first 6 months (CTCAE, version 5.0) before screening. 15. Unstable cardiovascular function: ? Myocardial infarction occurred within 6 months prior to enrollment; ? Have experienced unstable angina pectoris within 3 months prior to enrollment; ? Uncontrolled and clinically significant arrhythmias (such as persistent ventricular tachycardia, ventricular fibrillation, and torsion of the apex); ? Mobitz type II degree or III degree atrioventricular block; ? Congestive heart failure with a New York Heart Association rating of = 3; ? Left ventricular ejection fraction<50%. 16. Received major surgery < 4 weeks prior to enrollment; (minor surgeries such as catheter insertion and biopsy required by the protocol are not considered as exclusion criteria). 17. Inoculate with live virus vaccine within 28 days before enr
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Phase I: Safety Tolerance Evaluation;Phase II: The optimal overall response rate ORR (CR+PR) within 48 weeks of treatment (16 cycles) according to the LUGANO 2014 lymphoma evaluation criteria,; | — |
Secondary
| Measure | Time frame |
|---|---|
| Phase I:PK;Phase I: Pharmacodynamic Evaluation;Phase I: ADA and Nab;Phase I: Evaluation of anti-tumor activit;Phase II: Safety Evaluation;Phase II: Evaluation of anti-tumor activity;Phase II,PK;Phase II: Pharmacodynamic Evaluation;Phase II: ADA and Nab;The positive rate of MRD in NHL subjects who obtained CR using circulating tumor DNA evaluation; | — |
Countries
China
Contacts
Public ContactYuqin Song
Beijing Cancer Hospital
Outcome results
None listed