A Study of ATG-010 in Combination With Lenalidomide and Rituximab (R2) in Adults With DLBCL and iNHL

Inclusion Criteria:

1. Age ≥18 years.
2. Pathologically confirmed DLBCL (including de novo DLBCL or DLBCL transformed frompreviously diagnosed indolent lymphoma [e.g., follicular lymphoma]) or B-cell iNHLwith histological subtype limited to FL Grade 1, Grade 2, or Grade 3a or nodal orextranodal marginal zone lymphoma (MZL), based on criteria established by the WorldHealth Organization (WHO) 2016 classification.
3. Received at least 1 line of systemic therapy for the treatment of B-NHL.
4. Have evidence of relapse or refractory disease.
5. At least one bi-dimensionally measurable lesion per the Lugano 2014 Criteria (Cheson, 2014; Appendix 4).
6. Adequate bone marrow function at screening, defined as:

(1) absolute neutrophil count (ANC) ≥1.0 × 109/L (without hematopoietic stimulators such asgranulocyte or granulocyte-macrophage colony stimulating factor within 7 days prior totesting); (2) Platelet count ≥75 × 109/L; or ≥50 × 109/L when lymphoma infiltrates bonemarrow (without platelet transfusion or TPO, IL-11 and other hematopoietic stimulatingfactors administration within 7 days prior to testing); (3) Hemoglobin ≥80 g/L (without redblood cell transfusion or hematopoietic stimulating factor such as TPO administrationwithin 14 days prior to testing). 7. Adequate liver and kidney function, defined as:

1. Aspartate transaminase (AST) or alanine transaminase (ALT) ≤2.5 × upper limit ofnormal (ULN);
2. Serum total bilirubin ≤1.5 × ULN, or ≤3 ULN if have Gilbert syndrome;
3. Calculated creatinine clearance (CrCl) ≥60 mL/min for Dose Escalation Phase, and ≥30mL/min for Dose Expansion Phase, based on Cockcroft-Gault formula.
4. Eastern Cooperative Oncology Group (ECOG) performance status of ≤2. 9. Agree toeffective contraception during the study and within 12 months after the last dose of studytreatment.

Exclusion Criteria:

1. DLBCL with MALT lymphoma; composite lymphoma (Hodgkin's lymphoma+NHL); primarymediastinal (thymic) large B-cell lymphoma; Grade 3b follicular lymphoma.
2. Dose Escalation Phase: Subjects with known central nervous system involvement. DoseExpansion Phanse: Subjects with advanced lymphoma of the central nervous systeminvolvement at screening, however, subjects have stable central nervous systemlymphoma (in the case of no intracranial pressure or other conditions need medicalintervention) or do not occur disease progression as assessed by neurologicalsymptoms, signs, and radiography within 28 days prior to C1D1, will be consideredeligible.
3. Previous treatment with ATG-010 (selinexor) or other XPO1 inhibitors, or priorexposure to lenalidomide within 3 months before C1D1.
4. Contraindication to any drug in the combination therapy of SR2.
5. Use of any standard or experimental anti B-NHL therapy <21 days prior to C1D1,including chemotherapy, immunotherapy, radio-immunotherapy, nonpalliative radiation,or any other anticancer therapy.
6. Major surgery, or live vaccines received <28 days prior to C1D1.
7. ASCT <6 months or CAR-T cell infusion <6 months prior to the screening.
8. History of allogeneic hematopoietic stem cell transplant.
9. Any AE related with prior B-NHL treatment had not recovered to ≤Grade 1 (CTCAE, v5.0)or baseline at Screening (except alopecia, AE related to hematology and bloodbiochemistry; the values of hematology and biochemistry refer to inclusion criteria 7and 8).
10. Have active hepatitis B virus (HBV), hepatitis C virus (HCV) infections at screening.
11. Known serum HIV antibody positive or history of active HIV infection.
12. Active infection requiring intravenous antibiotics, antivirals, or antifungalstreatment within 14 days prior to C1D1; however, prophylactic use of these agents isacceptable (including intravenous medication).
13. Prior malignancy that required treatment or has shown evidence of recurrence (exceptfor non-melanoma skin cancer or adequately treated cervical carcinoma in situ) withinthe 2 years prior to C1D1.
14. Ischemic or hemorrhagic cerebrovascular disease, or gastrointestinal hemorrhage ≥Grade 3 (CTCAE, v5.0) within 6 months prior to screening.
15. History of deep vein thrombosis or pulmonary embolism within 12 months prior toscreening.
16. Inability to swallow tablets, malabsorption syndrome, or any other gastrointestinaldisease or dysfunction that could interfere with absorption of study treatment.
17. Inability or unwillingness to sign an ICF.
18. Existed any life-threatening illness, medical condition, or organ system dysfunctionwhich, in the Investigator's opinion, could compromise the subject's safety, or beingcompliant with the study procedures.