NT-I7 (Efineptakin Alfa), a Long-acting Human IL-7, Post-Axicabtagene Ciloleucel or Post-Lisocabtagene Maraleucel in Subjects With Relapsed/Refractory Large B-cell Lymphoma

NCT07052305 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 202512084
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

Diffuse large B-cell lymphoma is the most commonly occurring subtype of non-Hodgkin lymphoma, but treatment is often not curative, with as many as 50% of patients with adverse risk factors developing relapsed/refractory disease. CAR T-cell therapy has revolutionized modern cancer therapy, with axicabtagene ciloleucel and lisocabtagene maraleucel (anti-CD19 CAR T-cell therapies) FDA approved for second- or later-line treatment of relapsed/refractory large B-cell lymphoma. IL-7 plays a crucial role in T-cell homeostasis by inducing thymic differentiation, peripheral expansion, and extrathymic differentiation. It is the main regulator of T-cell hemostasis, inducing T-cell growth and proliferation in lymphopenic patients. There is data that suggests that exposure of T-cells to IL-7 may expand T-cells, prevent T-cell exhaustion, and improve effector functions. NT-I7 is a long-acting human IL-7 cytokine which has been shown in nonclinical studies to increase peripheral T-cells, antitumor efficacy, and tumor infiltrating lymphocytes, either as a monotherapy or in combination with chemo/radiotherapy and/or immune checkpoint inhibitors and CAR T therapy. This study is testing the hypothesis that the administration of NT-I7 following standard of care (SOC) approved CD19 CAR T-cell therapies for subjects with relapsed/refractory large B-cell lymphoma (LBCL) will be safe and tolerable and may increase the expansion and persistence of CAR T-cells in vivo, which may result in increased tumor response rate and improved clinical outcomes.

Conditions

Large B-cell Lymphoma

Keywords

Non-Hodgkins Lymphoma; Large B-cell Lymphoma; Yescarta; Axi-cel; Breyanzi; Liso-cel; Interleukin 7; NT-I7; CD19 CAR T-cell Therapy

Outcome Measures

Primary Outcomes (3)

• Incidence of adverse events

  Measured per CTCAE v 5.0. CRS and ICANS will be graded per ASTCT guidelines

  From start of CAR T-cell infusion (day 0) through day 90 (post CAR T-cell infusion)

• Maximum tolerated dose of NT-I7 (Dose Escalation only)

  Determined by incidence and nature of dose-limiting toxicities (DLTs). DLTs are defined in the protocol.

  From first dose of NT-I7 until 14 days after the second dose NT-I7 dose (estimated to be 35 days)

• Recommended phase 2 dose of NT-I7 (Dose Escalation only)

  Determined by the potential correlation of dose levels with safety and efficacy parameters.

  Through 90 days after CAR T-cell infusion

Secondary Outcomes (7)

• Overall response rate (ORR)

  Through completion of follow-up (estimated to be 1 year)

• Partial response (PR) rate

  Through completion of follow-up (estimated to be 1 year)

• Complete response (CR) rate

  Through completion of follow-up (estimated to be 1 year)

• Duration of response (DoR)

  Through completion of follow-up (estimated to be 1 year)

• Progression-free survival (PFS)

  Through completion of follow-up (estimated to be 1 year)

Study Arms (3)

Dose Escalation Dose Level 1 Starting Dose: NT-I7

EXPERIMENTAL

NT-I7 will be administered as an intramuscular injection at 600 μg/kg on Day 10 (-2/+5 days) and Day 31 (+/-3 days) post-CAR T-cell therapy infusion, with at least 2 weeks between the NT-I7 injections.

Dose Escalation Dose Level 2: NT-I7

EXPERIMENTAL

NT-I7 will be administered as an intramuscular injection at 720 μg/kg on Day 10 (-2/+5 days) and Day 31 (+/-3 days) post-CAR T-cell therapy infusion, with at least 2 weeks between the NT-I7 injections.

Dose Expansion (RP2D): NT-I7

EXPERIMENTAL

NT-I7 will be administered as an intramuscular injection at the recommended phase 2 dose on Day 10 (-2/+5 days) and Day 31 (+/-3 days) post-CAR T-cell therapy infusion, with at least 2 weeks between the NT-I7 injections.

Interventions

NT-I7 DRUG

Provided by NeoImmune Tech

Also known as: Efineptakin alfa

CAR T-cell therapy BIOLOGICAL

Standard of care: Will be given on day 0 and will be either axicabtagene ciloleucel or lisocabtagene maraleucel .

Also known as: Axicabtagene ciloleucel, Lisocabtagene maraleucel .

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed relapsed or refractory large B-cell lymphoma, including diffuse large B-cell lymphoma (DLBCL) not otherwise specified (NOS), high grade B-cell lymphoma, DLBCL arising from an indolent lymphoma, grade 3B follicular lymphoma and primary mediastinal large B-cell lymphoma.
• Measurable disease by IWG response criteria for lymphoma.
• Baseline FDG-PET/CT scan must show FDG-avid lesions compatible with CT-defined anatomical tumor sites.
• A previously irradiated lesion can be considered a target lesion if it is well defined, measurable, and has clearly progressed following radiation.
• FDG-PET/CT scans done as SOC up to 60 days pre-lymphodepletion therapy will be allowed. NOTE: After eligibility is confirmed, restaging FDG-PET/CT scans will not be used to change eligibility.
• Eligible for treatment with an FDA-approved SOC CD19 CAR T-cell therapy respective to the current FDA-approved CAR T-cell label for axi-cel(Yescarta®) or liso-cel (Breyanzi®).
• If the patient has previously received an autologous stem cell transplant, s/he must be at least 3 months post-transplant.
• At least 18 years of age.
• ECOG performance status ≤ 2
• Adequate bone marrow and organ function at the start of lymphodepleting chemotherapy as pre-conditioning for SOC CD19 CAR T-cell infusion as defined below:
• Absolute neutrophil count ≥ 1.0 K/cumm
• Platelets ≥ 50 K/cumm
• Hemoglobin ≥ 8.0 g/dL
• Total bilirubin ≤ 1.5 x IULN or direct bilirubin ≤ IULN for patients with total bilirubin levels \> 1.5 x IULN (except for patients with Gilbert's syndrome, who must have a baseline total bilirubin ≤ 3.0 mg/dL)
• AST(SGOT)/ALT(SGPT) ≤ 2.5 x IULN (except for patients with documented liver involvement or bone metastases, who must have an AST and/or ALT ≤ 5.0 x IULN)

You may not qualify if:

• Previous receipt of an allogeneic solid organ transplant or bone marrow transplant.
• Prior or concurrent malignancy whose natural history has the potential to interfere with the safety or efficacy assessment of the investigational regimen. Patients with prior or concurrent malignancy that does NOT meet that definition are eligible for this trial.
• Chemotherapy or biologic or hormonal therapy for prior or concurrent cancer treatment, within 14 days prior to the first NT-I7 injection.
• NOTE: Concurrent use of hormones for non-cancer-related conditions (e.g., insulin for diabetes, hormone replacement therapy) is acceptable.
• Currently receiving any other investigational agents, or received within 14 days prior to the first NT-I7 injection.
• Documented active central nervous system (CNS) involvement by lymphoma.
• A history of allergic reactions attributed to compounds of similar chemical or biologic composition to NT-I7 or other agents used in the study.
• Uncontrolled intercurrent illness including, but not limited to:
• Ongoing or active infection (including active hepatitis A or mycobacterium tuberculosis (testing not required))
• Congestive heart failure with NYHA Class ≥ 2
• Uncontrolled atrial fibrillation
• Any of the following within 6 months prior to day of CAR T-cell administration:
• Unstable angina pectoris
• Myocardial infarction
• Coronary artery bypass grafting

Sponsors & Collaborators

• Daniel E Corbin Lymphoma Research Fund: collaborator
• Washington University School of Medicine: lead
• NeoImmuneTech: collaborator
• The Foundation for Barnes-Jewish Hospital: collaborator

Study Sites (1)

Washington University School of Medicine

St Louis, Missouri, 63110, United States

RECRUITING

Related Links

• Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

MeSH Terms

Conditions

Lymphoma, Non-Hodgkin

Interventions

efineptakin alfa; Immunotherapy, Adoptive; axicabtagene ciloleucel

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Adoptive Transfer; Immunization, Passive; Immunization; Immunotherapy; Immunomodulation; Biological Therapy; Therapeutics; Immunologic Techniques; Investigative Techniques

Study Officials

• Zachary D Crees, M.D.

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Zachary D Crees, M.D.

CONTACT

314-273-1039; zcrees@wustl.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 26, 2025
• First Posted: July 4, 2025
• Study Start: February 10, 2026
• Primary Completion (Estimated): November 30, 2027
• Study Completion (Estimated): August 31, 2028
• Last Updated: April 9, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)