IKS03 in Patients with Advanced B Cell Non-Hodgkin Lymphomas

Inclusion Criteria:

1. Males or females, ≥ 18 years of age

2. Part 1: documented B cell NHL (any subtype except Burkitt lymphoma, Waldenströmmacroglobulinemia, chronic lymphocytic leukemia); previously confirmed CD19-positiveif feasible

3. Part 2: documented B cell NHL (subtypes to be determined); confirmed CD19-positive;possible expansion cohorts may include:

4. Diffuse large B cell lymphoma (including germinal center B cell type, activatedB cell type)

5. Follicular lymphoma (including duodenal-type follicular lymphoma)

6. Mantle cell lymphoma

7. B cell lymphomas not specified

8. If B cell NHL subtype likely to have bone marrow involvement must be willing toundergo bone marrow biopsy in the event of an on-study complete response to confirmresponse

9. NHL that is relapsed, refractory to, or intolerant of existing therapy(ies) withknown curative potential, or for which no standard therapy is available; must havereceived at least 2 prior lines of systemic therapy

10. Must be in need of systemic treatment and not require immediate cytoreductivetherapy

11. Part 1: measurable or non-measurable disease

12. Part 2: measurable disease according to The Revised Criteria/Lugano Classification

13. Part 1: screening tumor biopsy requested, but optional; Part 2: patient must agreeto screening tumor biopsy

14. ECOG performance status 0 or 1; anticipated life expectancy ≥ 10 weeks

15. Women of childbearing potential and fertile men agreeing to use two effectivemethods of contraception (including a highly effective method of contraception);women beginning 2 weeks prior to the first dose, men beginning prior to the firstdose, and both continuing until 8 months after the last dose of study drug; malepatients must also agree to refrain from sperm donation during this period.

16. Ability to understand and give written informed consent

Exclusion Criteria:

1. Women who are pregnant or intending to become pregnant before, during, or within 8months after the last dose of study drug; women who are breastfeeding

2. Patients documented to be CD19-negative

3. Central nervous system (CNS) lymphoma, leptomeningeal infiltration, or spinal cordcompression not controlled by prior surgery or radiotherapy; symptoms suggesting CNSinvolvement

4. Part 2: History of another malignancy within 2 years, with the exception of:

5. Treated, non-melanoma skin cancers

6. Treated carcinoma in situ (e.g., breast, cervix)

7. Controlled, superficial carcinoma of the urinary bladder

8. T1a or b prostate carcinoma treated according to standard of care, with PSAwithin normal limits

9. Papillary thyroid carcinoma Stage I treated surgically for cure

10. Any of the following hematologic abnormalities at baseline (transfusion allowed > 5days previous):

11. Hemoglobin < 8.0 g/dL

12. Absolute neutrophil count < 1,000 per mm3

13. Platelet count < 75,000 per mm3

14. Any of the following laboratory abnormalities at baseline:

15. Total bilirubin > 1.5 × upper limit of normal (ULN); > 3 × ULN if withGilbert's Syndrome

16. AST or ALT > 3 × ULN; > 5 × ULN if due to hepatic involvement by tumor

17. Estimated GFR ≤ 60 mL/min corrected for BSA

18. Albuminuria defined as urine albumin to creatinine ratio < 30 mg/g or < 3mg/mmol) by spot urine albumin

19. Any of the following coagulation parameter abnormalities at baseline unless on astable dose of anticoagulant therapy for a prior thrombotic event:

20. PT or INR > 1.5 × ULN; > 3× ULN if anticoagulated)

21. PTT > 1.5 × ULN; > 3× ULN if anticoagulated

22. Any of the following laboratory abnormalities at baseline aimed at assessing renalfunction:

23. Estimated glomerular filtration rate (eGFR) ≤ 60 mL/min, corrected for BSA.

24. Albuminuria defined as urine albumin to creatinine ratio (UACR) ≥ 30 mg/g or ≥ 3 mg/mmol by spot urine albumin

25. Patients with:

26. Active thrombosis, or a history of deep vein thrombosis or pulmonary embolism,within 4 weeks unless adequately treated and stable

27. Active uncontrolled bleeding or a known bleeding diathesis

28. Significant cardiovascular disease or condition, including:

29. Congestive heart failure or angina pectoris requiring therapy

30. Ventricular arrhythmia requiring therapy or other uncontrolled arrhythmia

31. Severe conduction disturbance (e.g., 3rd degree heart block)

32. QTc interval ≥ 480 milliseconds

33. Left ventricular ejection fraction below the lower limit of normal or < 50% byMUGA scan or echocardiogram

34. Class III or IV cardiovascular disease according to the New York HeartAssociation Functional Classification

35. History of acute coronary syndromes (e.g., MI, unstable angina), coronaryangioplasty, stenting, or bypass within 6 months

36. Significant liver disease, including:

37. Non-infectious hepatitis

38. Hepatic cirrhosis (Child-Pugh Class B and Class C)

39. Significant pulmonary disease or condition, including:

40. Significant symptomatic COPD, as assessed by the Investigator

41. History or any current evidence on imaging studies of interstitial lungdisease, pulmonary fibrosis

42. History of pulmonary inflammatory disease, pneumonitis, ARDS

43. History of pneumonia within 6 months

44. Significant corneal disease or condition, including history of or current evidenceof keratitis

45. Clinically significant CNS disease or condition including PML, epilepsy, vasculitis,or neurodegenerative disease. Also including TIA or stroke within 6 months

46. Known HIV infection or AIDS

47. Active hepatitis B virus or hepatitis C virus infection

48. Any other serious/active/uncontrolled infection, any infection requiring parenteralantibiotics, or unexplained fever > 38ºC within 2 weeks

49. Autoimmune disease or condition requiring systemic steroids or otherimmunosuppressive medications

50. Unresolved Grade > 1 AE associated with any prior antineoplastic therapy (exceptpersistent Grade 2 alopecia, peripheral neuropathy, decreased hemoglobin,neutropenia, lymphopenia, hypomagnesemia, and/or endocrine end-organ failure beingadequately managed by HRT)

51. Known or suspected hypersensitivity to any of the excipients of formulated studydrug

52. Inadequate recovery from a surgical procedure, or a major surgical procedure within 4 weeks

53. Any other serious, life-threatening, or unstable preexisting medical condition,including significant organ system dysfunction, or clinically significant laboratoryabnormality(ies)

54. A psychiatric disorder or altered mental status that would preclude understanding ofthe informed consent process

Drugs and Other Treatments to be Excluded:

1. Receipt of:

2. Any CD19-targeted therapy within 3 months

3. Any tumor vaccine within 6 weeks (must have progressed if previously received)

4. Prior autologous/allogeneic CAR-T therapy if known to be CD19-negative after

5. Any other antineoplastic agent for the primary malignancy without delayed toxicitywithin 4 weeks or 5 plasma half-lives, whichever is shortest (except nitrosoureasand mitomycin C within 6 weeks)

6. Any other investigational treatments within 4 weeks

7. Drugs known to impair renal function, including:

8. NSAIDS within 3 days

9. Aminoglycoside antibiotics, amphotericin B, etc. within 1 week

10. Bisphosphonates within 1 month

11. Prior solid organ transplant

12. Allogeneic HSCT within 6 months, or:

13. If receiving immunosuppression

14. If with active evidence of GVHD

15. Autologous hematopoietic stem cell transplantation (HSCT) within 3 months

16. Radiotherapy:

17. To target lesions within 4 weeks unless progression of the lesion has beendocumented

18. To non-target lesions within 1 week

19. Live/live-attenuated vaccines against infectious diseases within 4 weeks

20. Immunosuppressive or systemic glucocorticoid therapy (> 10 mg prednisone daily orequivalent) within 2 weeks

21. Prophylactic use of hematopoietic growth factors within 1 week

22. Herbal therapies and supplements within 2 weeks

23. Strong inhibitors of cytochrome P450 within 2 weeks