Relapsed/Refractory Large B-cell Lymphoma With NT-I7 Post-CD19 CAR T-cell Therapy

Subjects must meet all the following criteria for study entry:

1. Must be ≥18 years on the day of signing informed consent.
2. Be willing and able to provide written informed consent/assent for the study.
3. Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1
4. Subjects should be eligible for CAR-T therapy respective to the current FDA-approvedCAR-T label for Yescarta, Breyanzi, or Kymriah.
5. Subjects with histologically confirmed relapsed or refractory LBCL including diffuselarge B-cell lymphoma (DLBCL) not otherwise specified (NOS), high grade B-celllymphoma,DLBCL arising from follicular lymphoma, and primary mediastinal large B-celllymphoma, must be eligible for SOC CD19 CAR T-cell Therapy. (a) Tumor tissue (fresh or archival) must have been tested to confirm the type ofLBCL.
6. Subjects must have measurable disease by IWG response criteria for lymphoma [Luganoclassification (3)]
7. Baseline fluorodeoxyglucose (FDG)-PET/computed tomography (CT) scans must showpositive lesions compatible with CT-defined anatomical tumor sites but will notbe used in subsequent clinical decisions.
8. A previously irradiated lesion can be considered a target lesion if the lesion iswell defined, measurable, and has clearly progressed.
9. Subjects that received bridging therapy pre-lymphodepletion will be allowed forenrollment regardless of re-staging results (PMR or CMR), even if the lesion isnot measurable per the criteria mentioned above.
10. PET/CT scans done as SOC up to 28 days pre-lymphodepletion therapy will beallowed. All subjects whose scans are > 28 days from lymphodepletion therapy will need are-staging FDG-PET/CT scan.
11. (This is a placeholder for inclusion criterion 7, which has been removed.)
12. Subjects must have a life expectancy of greater than or equal to 12 weeks perassessment from the enrolling physician.
13. Adequate organ and marrow function per institutional guidelines at the start oflymphodepleting chemotherapy as pre-conditioning for SOC CD19 CAR T-cell infusion. The following laboratory parameters (9a-h) are recommendations. Labs outside of theseranges may be considered for inclusion after consultation with the medical monitor.Cytopenia resulting from disease or bridging therapy will not be considered exclusionary.
14. Hemoglobin ≥8.0 g/dL or ≥4.96 mmol/L
15. Absolute neutrophil count ≥1,000/µL
16. Platelets >50,000/µL
17. Total bilirubin ≤1.5 × institutional upper limit of normal (ULN) OR direct bilirubin ≤ULN for subjects with total bilirubin levels >1.5 × ULN, except subject withdocumented Gilbert's syndrome (>3 x ULN), who must have a baseline total bilirubin ≤ 3.0 mg/dL
18. AST(SGOT)/ALT(SGPT) ≤2.5 × ULN (AST and/or ALT ≤5 × ULN for subjects with livermetastasis)
19. Alkaline phosphatase ≤2.5 × ULN (≤5 × ULN for subjects with documented liverinvolvement or bone metastases)
20. Creatinine clearance (CrCl) ≥30 mL/min as calculated per institutional standard.
21. INR and aPTT ≤1.5 × ULN unless subject is receiving anticoagulant therapy as long asPT or aPTT is within therapeutic range of intended use of anticoagulants 10. Femalesubjects who are either postmenopausal for at least 1 year, are surgically sterile forat least 6 weeks; female subjects of childbearing potential must agree to remainabstinent (refrain from heterosexual intercourse) or to use dual methods ofcontraception for the duration of study treatment and for 90 days after NT-I7injection, whichever is longer. Female subjects of childbearing potential (includingwomen who have had a tubal ligation) must have a negative serum or urine pregnancytest within 72 hours prior to NT-I7 injection. If the urine test is positive, orcannot be confirmed as negative, a serum pregnancy test will be required.
22. ECG demonstrating Fridericia's corrected QT interval (QTcF) < 500 ms. Patientswith QTcF ≥ 500 ms will require clearance by a local cardiologist.

Exclusion Criteria: Subjects meeting any of the following criteria are not eligible for enrollment in thestudy:

1. In Dose Escalation phase: Grade ≥3 CRS or ICANS post-CD19 CAR T-cell infusion.Note: Grade 1 or 2 CRS or ICANs must be completely resolved >3 days prior toNT-I7 injection
2. In Dose Expansion phase: Grade ≥3 CRS or ICANS post-CD19 CAR T-cell infusion.Note: Grade 1 or 2 CRS or ICANS must be completely resolved >3 days prior toNT-I7 injection
3. Pregnant, lactating or breastfeeding or expecting to conceive or father childrenwithin the study duration from screening through 120 days after the last dose ofstudy treatment.
4. This exclusion criteria has been removed and remains as a placeholder.
5. Subjects with documented current central nervous system (CNS) involvement bylymphoma are to be excluded from study participation.
6. Any concurrent chemotherapy or biologic or hormonal therapy for cancer treatment. Note: Concurrent use of hormones for noncancer-related conditions (e.g., insulinfor diabetes and hormone replacement therapy) is acceptable. In addition, localtreatment (eg, by local surgery or radiotherapy) of isolated lesions forpalliative intent is acceptable beyond the DLT evaluation period with priorconsultation and agreement with the medical monitor.
7. Subjects who have autoimmune disease history for the past 2 years, including butnot limited to systemic lupus erythematosus, rheumatoid arthritis, inflammatorybowel disease, vascular thrombosis associated with antiphospholipid syndrome,Wegener's granulomatosis, Sjögren's syndrome, Bell's palsy, Guillain-Barresyndrome, multiple sclerosis, vasculitis, or glomerulonephritis. The followingare exceptions to this criterion:
8. Subjects with vitiligo or alopecia.
9. Subjects with type 1 diabetes mellitus.
10. Subjects with hypothyroidism (e.g., following Hashimoto syndrome) stable onhormone replacement
11. Psoriasis not requiring systemic treatment.
12. NOTE: Diverticulitis that is not associated with inflammatory bowel diseaseis not considered exclusionary (e.g., subjects who do not have activediarrhea due to chronic diverticulitis).
13. Have active and clinically relevant bacterial, fungal, viral, or TB infection,including known Hepatitis A, B, or C or HIV (testing not required).
14. Concurrent enrollment in another clinical study unless it is an observational (noninterventional) clinical study.
15. Receipt of any conventional or investigational anticancer therapy, not otherwisespecified above, within 30 days prior to NT-I7 injection.
16. Unresolved toxicities from prior anticancer therapy, defined as having notresolved to NCI CTCAE v5.0 Grade ≤ 1 with the exception of alopecia andlaboratory values listed per the inclusion criteria. Subjects with irreversibletoxicity that is not reasonably expected to be exacerbated by any of theinvestigational products may be included (e.g., hearing loss, peripheralneuropathy) after consultation with the medical monitor.
17. Receipt of live, attenuated vaccine within 30 days prior to NT-I7 injection.Note: Subjects, if enrolled, should not receive live vaccine during the study andthrough 30 days after NT-I7 injection, whichever is longer. The administration ofkilled vaccines is permitted at any time.
18. Has had an allogenic tissue/solid organ transplant or bone marrow transplant.
19. Subjects for whom intramuscular therapy is contraindicated.
20. Has clinically significant cardiac disease, including, but not limited to, any ofthe following:
21. Uncontrolled atrial fibrillation
22. Congestive Heart Failure NYHA Class ≥ 2
23. Or any of the following within 6 months prior to Baseline, Day 0 CAR-Tadministration:

• Unstable angina
• Myocardial infarction
• Coronary artery bypass grafting
• Coronary angioplasty
• Coronary stenting
• Clinically significant cardiac arrhythmia and/or conduction abnormality

4. History of other clinically significant cardiac disease that, in the opinion ofthe Investigator or designee, is a contraindication to study treatment is alsoexcluded.