A Phase 1 Study of JV-213 Autologous CD79b-targeting Chimeric Antigen Receptor T-cell Therapy in Adults With Relapsed or Refractory B-cell Lymphomas

Inclusion Criteria:

Patients must meet the following inclusion criteria in order to be eligible for participation in this trial:

1. For the dose escalation cohort: Eligible patients will include those with r/r B-celllymphoma including LBCL (DLBCL, HGBCL, LBCL transformed from indolent lymphoma, andPMBCL), FL, marginal zone lymphoma, and MCL after at least 2 prior systemictherapies and Burkitt lymphoma after at least 1 prior systemic therapy. For the doseexpansion cohort: Patients with r/r LBCL (DLBCL, HGBCL, LBCL transformed fromindolent lymphoma, and PMBCL) and FL grade 3B will be eligible

2. Received at least 2 prior lines of therapy, including anti-CD20 antibody andanthracycline therapy for LBCL, anti-CD20 antibody and alkylating agent orlenalidomide therapy for FL, anti-CD20 antibody and alkylating agent or lenalidomideor BTK inhibitor therapy for marginal zone lymphoma, and anti-CD20 antibody andalkylating agent or BTK inhibitor therapy for MCL. Patients with Burkitt lymphomamay be eligible after 1 line of prior therapy including anti-CD20 antibody andanthracycline therapy.

3. Patients who have received prior CD19 CAR cell therapy using FMC63 antibody fortargeting CD19 are eligible and must be at least 6 weeks post CAR infusion and have <5% of peripheral blood T cells expressing the prior CAR by flow cytometryassessment.

4. ≥18 years of age

5. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1

6. At least one measurable lesion per the Lugano 2014 Classification53

7. At least two weeks or 5 half-lives, whichever is shorter, must have elapsed sinceany prior systemic anti-cancer therapy prior to leukapheresis. For patients treatedwith monoclonal antibody-based therapies, at least 4 weeks must have elapsed priorto leukapheresis.

8. Toxicities due to prior therapy must be stable and recovered to ≤grade 1 (except forclinically non-significant toxicities such as alopecia)

≥1.0×10^9/L

10. Absolute lymphocyte count of ≥0.1×10^9/L

11. Platelet count of ≥75×10^9/L

12. Creatinine clearance (as estimated by Cockcroft Gault) ≥45 mL/min

13. Serum alanine transaminase (ALT) / aspartate transaminase (AST) ≤5 times the upperlimit of normal (ULN)

14. Total bilirubin ≤2 mg/dL, except in patients with Gilbert's syndrome.

15. Cardiac ejection fraction ≥45% with no evidence of clinically significantpericardial effusion

16. Baseline oxygen saturation ≥92% on room air

17. Women of childbearing potential must have a negative serum or urine pregnancy test (women who have had hysterectomy and women who are over the age of 45 years and

Exclusion Criteria:

Patients will be excluded from participating in the trial if he/she has:

1. Active central nervous system (CNS) lymphoma including patients with detectablecerebrospinal fluid malignant cells or brain metastases. Patients with prior CNSlymphoma that has been effectively treated will be eligible if treatment wascompleted at least one year prior to enrolment and there is no evidence of diseaseon MRI with gadolinium contrast at the time of screening.

2. Any CAR cell therapy using non-FMC63 antibody.

3. History of Richter's transformation of chronic lymphocytic leukemia

4. Autologous stem cell transplantation within 6 weeks.

5. Allogeneic stem cell transplantation within 3 months or active graft versus hostdisease.

6. Active autoimmune disease (e.g. Crohn's disease, rheumatoid arthritis, systemiclupus erythematosus) requiring systemic immunosuppression/systemic disease modifyingagents within the last 1 year or inflammatory disease (including graft versus hostdisease) requiring systemic immunosuppressive therapy. Physiological replacement ofcorticosteroids of up to 7.5 mg of prednisone or equivalent per day, and topical andinhaled corticosteroids are permitted.

7. History of any form of primary immunodeficiency that in the opinion of theinvestigator may affect efficacy of the CAR-T product.

8. History of any one of the following cardiovascular conditions within the past 6months: Class III or IV heart failure as defined by the New York Heart Association,cardiac angioplasty or stenting, myocardial infarction, unstable angina, or otherclinically significant cardiac disease.

9. History of malignancy other than nonmelanoma skin cancer or carcinoma in situ (e.g.cervix, bladder, breast) unless disease free for at least 2 years and treated withcurative intent. Patients with a prior history of malignancy whose natural historyor treatment (e.g. hormonal therapy) does not have the potential to interfere witheither the safety or efficacy assessment of the investigational regimen in theopinion of the investigator may be included.

10. Presence of fungal, bacterial, viral, or other infection that is uncontrolled orrequiring intravenous antimicrobials for management. Simple urinary tract infectionand uncomplicated bacterial pharyngitis or localized skin infections are permittedif responding to active treatment and after consultation with the PrincipalInvestigator.

11. Known history of infection with HIV or hepatitis B (HBsAg positive) or hepatitis Cvirus (anti-HCV positive). A history of hepatitis B or hepatitis C is permitted ifthe viral load is undetectable per quantitative PCR and/or nucleic acid testing.

12. History or presence of CNS disorders such as seizure disorder, cerebrovascularischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease withCNS involvement

13. Patients with cardiac atrial or cardiac ventricular lymphoma involvement

14. Requirement for urgent therapy due to tumor mass effect such as bowel obstruction orblood vessel compression

15. Any medical condition likely to interfere with assessment of safety or efficacy ofstudy treatment

16. Live vaccine ≤6 weeks prior to planned start of conditioning regimen

17. Women of child-bearing potential who are pregnant or breastfeeding because of thepotentially dangerous effects of the conditioning chemotherapy on the fetus orinfant.

18. Females of childbearing potential and males of child fathering potential who are notwilling to practice two methods of birth control from the time of consent through 6months after infusion of the study drug

19. In the investigator's judgment, the patient is unlikely to complete allprotocol-required study visits or procedures, including follow-up visits, or complywith the study requirements for participation.