NKTR-255 in Combination With CAR-T Cell Therapy for the Treatment of Relapsed or Refractory Large B-cell Lymphoma

NCT05359211 | Active Not Recruiting Phase 1 DMC FDA Drug

• 3 other identifiers: RG1122036NCI-2022-0231610802
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 1

Brief Summary

This phase Ib trial studies the effects of NKTR-255 in combination with chimeric antigen (CAR)-T cell therapy and to see how well they work in treating patients with large B-cell lymphoma that has come back (relapsed) or does not respond to treatment (refractory). NKTR-255 is an investigational IL-15 receptor agonist designed to boost the immune system's natural ability to fight cancer. T cells are infection fighting blood cells that can kill tumor cells. Lisocabtagene maraleucel is a CAR-T cell product that consists of genetically engineered T cells, modified to recognize CD19, a protein on the surface of cancer cells. These CD19-specific T cells may help the body's immune system identify and kill CD19-positive cancer cells. Giving NKTR-255 together with lisocabtagene maraleucel may work better in treating large B-cell lymphoma than either drug alone.

Conditions

Recurrent Diffuse Large B-Cell Lymphoma; Recurrent Diffuse Large B-Cell Lymphoma, Not Otherwise Specified; Recurrent Grade 3b Follicular Lymphoma; Recurrent Primary Mediastinal Large B-Cell Lymphoma; Refractory Diffuse Large B-Cell Lymphoma; Refractory Diffuse Large B-Cell Lymphoma, Not Otherwise Specified; Refractory Grade 3b Follicular Lymphoma; Refractory Primary Mediastinal Large B-Cell Lymphoma; Transformed Indolent B-Cell Non-Hodgkin Lymphoma to Diffuse Large B-Cell Lymphoma

Outcome Measures

Primary Outcomes (4)

• Incidence of adverse events (AEs)

  Grade ≥ 3 AEs considered related to NKTR-255 will be listed and summarized. Summaries of grade ≥ 3 laboratory data will include, at a minimum, treatment-emergent laboratory abnormalities. Summaries of AEs and laboratory abnormalities will be based on the safety evaluable population.

  30 days after the last dose of NKTR-255 or until a new antitumor therapy has been initiated

• Dose-limiting toxicity (DLT) rates

  Observed DLT rates will be summarized based on the DLT evaluable population. Final DLT rates at each dose level will be estimated by isotonic regression by applying the pooled adjacent violators algorithm.

  Up to 21 days after the first NKTR-255 infusion

• Optimal biological dose (OBD)

  A composite of clinical information will be utilized to determine the OBD based on safety and tolerability, confirmation of maximum target engagement, optimal biological effects without undesirable clinical effects, pharmacokinetic parameters, and biological response data.

  Up to 12 months after the CAR-T cell infusion

• Complete response (CR) rate

  The CR rate will be summarized along with the 2-sided 95% exact Clopper-Pearson confidence interval based on the efficacy evaluable population.

  Up to 3 months after the CAR-T cell infusion

Secondary Outcomes (4)

• Complete response (CR) and overall response (OR) rates

  Up to 12 months after the CAR-T cell infusion

• Duration of response (DOR)

  Up to 12 months after the CAR-T cell infusion

• Progression free survival (PFS)

  Up to 12 months after the CAR-T cell infusion

• Overall survival (OS)

  Up to 12 months after the CAR-T cell infusion

Study Arms (1)

Treatment (lymphodepletion, liso-cel, NKTR-255)

EXPERIMENTAL

Patients receive standard of care lymphodepletion therapy consisting of cyclophosphamide and fludarabine on days -5 to -3 followed by liso-cel CAR-T cell infusion on day 0. Patients then receive NKTR-255 IV over 30 minutes every 3 weeks starting on day 10 or 14 for up to 3 doses in the absence of disease progression or unacceptable toxicity. Patients undergo chest x-ray and ECHO or MUGA during screening. Patients undergo bone marrow biopsy and aspiration, LP for CSF sample collection during screening, on the study and during follow-up as clinically indicated. Patients also undergo PET/CT throughout the trial. Additionally, patients undergo blood sample collection and may optionally undergo tissue biopsy throughout the trial.

Drug: Cyclophosphamide; Drug: Fludarabine; Biological: Lisocabtagene Maraleucel; Drug: Polymer-conjugated IL-15 Receptor Agonist NKTR-255; Procedure: X-Ray Imaging; Procedure: Echocardiography; Procedure: Multigated Acquisition Scan; Procedure: Bone Marrow Biopsy; Procedure: Bone Marrow Aspiration; Procedure: Lumbar Puncture; Procedure: Computed Tomography; Procedure: Positron Emission Tomography; Procedure: Biospecimen Collection; Procedure: Biopsy

Interventions

Cyclophosphamide DRUG

Given IV

Also known as: (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Carloxan, Ciclofosfamida, Ciclofosfamide, Cicloxal, Clafen, Claphene, CP monohydrate, CTX, CYCLO-cell, Cycloblastin, Cycloblastine, Cyclophospham, Cyclophosphamid monohydrate, Cyclophosphamide Monohydrate, Cyclophosphamidum, Cyclophosphan, Cyclophosphane, Cyclophosphanum, Cyclostin, Cyclostine, Cytophosphan, Cytophosphane, Cytoxan, Fosfaseron, Genoxal, Genuxal, Ledoxina, Mitoxan, Neosar, Revimmune, Syklofosfamid, WR- 138719, Asta B 518, B-518

Treatment (lymphodepletion, liso-cel, NKTR-255)

Fludarabine DRUG

Given IV

Also known as: Fluradosa

Treatment (lymphodepletion, liso-cel, NKTR-255)

Lisocabtagene Maraleucel BIOLOGICAL

Given IV

Also known as: Anti-CD19-CAR Genetically Engineered Autologous T Lymphocytes JCAR017, Anti-CD19-CAR Genetically Engineered Autologous T-lymphocytes JCAR017, Autologous Anti-CD19-EGFRt-4-1BB-zeta-modified CAR CD8+ and CD4+ T-lymphocytes JCAR017, Breyanzi, JCAR 017, JCAR017, Liso-cel

Treatment (lymphodepletion, liso-cel, NKTR-255)

X-Ray Imaging PROCEDURE

Undergo x-ray imaging

Also known as: Conventional X-Ray, Diagnostic Radiology, Medical Imaging, Plain film radiographs, Radiographic Imaging

Treatment (lymphodepletion, liso-cel, NKTR-255)

Echocardiography PROCEDURE

Undergo ECHO

Also known as: EC

Treatment (lymphodepletion, liso-cel, NKTR-255)

Multigated Acquisition Scan PROCEDURE

Undergo MUGA

Also known as: Blood Pool Scan, Equilibrium Radionuclide Angiography, Gated Blood Pool Imaging, MUGA, MUGA Scan, Multi-Gated Acquisition Scan, Radionuclide Ventriculogram Scan, Synchronized Multigated Acquisition Scanning, RNVG, SYMA Scanning

Treatment (lymphodepletion, liso-cel, NKTR-255)

Bone Marrow Biopsy PROCEDURE

Undergo bone marrow biopsy and aspiration

Also known as: Biopsy of Bone Marrow

Treatment (lymphodepletion, liso-cel, NKTR-255)

Bone Marrow Aspiration PROCEDURE

Undergo bone marrow biopsy and aspiration

Treatment (lymphodepletion, liso-cel, NKTR-255)

Lumbar Puncture PROCEDURE

Undergo LP

Also known as: LP, spinal tap

Treatment (lymphodepletion, liso-cel, NKTR-255)

Computed Tomography PROCEDURE

Undergo PET/CT

Also known as: CAT Scan, Computed Axial Tomography, CT, CT SCAN

Treatment (lymphodepletion, liso-cel, NKTR-255)

Positron Emission Tomography PROCEDURE

Undergo PET/CT

Also known as: Medical Imaging, PET, PET scan, Positron-Emission Tomography, proton magnetic resonance spectroscopic imaging, PT

Treatment (lymphodepletion, liso-cel, NKTR-255)

Biospecimen Collection PROCEDURE

Undergo blood and CSF sample collection

Also known as: Biological Sample Collection

Treatment (lymphodepletion, liso-cel, NKTR-255)

Biopsy PROCEDURE

Undergo tissue biopsy

Also known as: Bx

Treatment (lymphodepletion, liso-cel, NKTR-255)

Polymer-conjugated IL-15 Receptor Agonist NKTR-255 DRUG

Given IV

Also known as: IL-15 Receptor Agonist NKTR-255, Long-acting Polymer-conjugated IL-15, NKTR 255, NKTR-255, NKTR255

Treatment (lymphodepletion, liso-cel, NKTR-255)

Eligibility Criteria

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

You may qualify if:

• Male or female \>= 18 years of age at the time of consent
• Patients with LBCL (including diffuse large B-cell lymphoma \[DLBCL\] not otherwise specified \[including DLBCL arising from indolent lymphoma\], high-grade B-cell lymphoma, primary mediastinal large B-cell lymphoma, and follicular lymphoma grade 3B) with a Food and Drug Administration (FDA)-approved indication for treatment with liso-cel
• Fludeoxyglucose F-18 (FDG)-avid disease on positron emission tomography (PET) imaging or pathology evidence of active disease
• Evidence of CD19 expression on any prior or current tumor specimen or a high likelihood of CD19 expression based on disease histology
• Karnofsky performance status \>= 60%
• Absolute neutrophil count (ANC) \>= 1000 cells/mm\^3 in the absence of bone marrow involvement by lymphoma
• Platelets \>= 50,000 cells/mm\^3 in the absence of bone marrow involvement by lymphoma
• Hemoglobin \>= 8 g/dL in the absence of bone marrow involvement by lymphoma
• Calculated creatinine clearance (Cockcroft/Gault) \> 30 mL/min/1.73 m\^2
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =\< 3 x ULN (or \< 5 x ULN for subjects with lymphomatous infiltration of the liver)
• Total bilirubin =\< 2 (or \< 3.0 for subjects with Gilbert's syndrome or lymphomatous infiltration of the liver)
• Common Terminology Criteria for Adverse Events (CTCAE) Grade =\< 1 dyspnea
• Saturation of oxygen (Sa02) \>= 92% on room air
• Patients with clinically significant pulmonary dysfunction, as determined by medical history and physical exam should undergo pulmonary function testing and must have a forced expiratory volume in 1 second (FEV1) of \>= 50% of predicted value
• Patients with clinically significant pulmonary dysfunction, as determined by medical history and physical exam should undergo pulmonary function testing and must have a diffusing capacity of the lung for carbon monoxide (DLCO; corrected) \>= 40% of predicted value

You may not qualify if:

• Planned use of therapeutic doses of corticosteroids (\> 20 mg/day prednisone or equivalent) or other systemic immunosuppression within 7 days prior to leukapheresis or within 72 hours prior to liso-cel infusion. Topical and/or inhaled steroids are permitted
• Prior treatment with any CD19 CAR-T cell therapy
• For allogeneic hematopoietic cell transplant (HCT) recipients, active graft versus host disease (GVHD) and/or systemic GVHD therapy within 30 days prior to planned leukapheresis
• Known active hepatitis B (detectable hepatitis B deoxyribonucleic acid \[DNA\]) or hepatitis C (detectable hepatitis C ribonucleic acid \[RNA\])
• Known human immunodeficiency virus (HIV) infection
• Pregnant or breastfeeding women
• Prior treatment with any IL-2 or IL-15 agonist and/or biosimilar agents
• Active autoimmune or inflammatory disorders (including inflammatory bowel disease \[e.g., ulcerative colitis, Crohn's disease\], celiac disease, or other serious chronic gastrointestinal conditions associated with diarrhea, autoimmune vasculitis, systemic lupus erythematosus, Wegener syndrome \[granulomatosis with polyangiitis\], myasthenia gravis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc.) requiring immunosuppressive therapy. The following are exceptions to this criterion:
• Vitiligo.
• Alopecia.
• Hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement.
• Type 1 diabetes mellitus.
• Psoriasis not requiring systemic treatment.
• Conditions considered to be low risk of serious deterioration by the principal investigator (PI).
• History of any one of the following cardiovascular conditions within the past 6 months: class III or IV heart failure as defined by the New York Heart Association (NYHA), cardiac angioplasty or stenting, myocardial infarction, or unstable angina; unless clearance by a cardiologist is obtained. History of other clinically significant cardiac disease that, in the opinion of the PI or designee, is a contraindication to study treatment is also excluded

Sponsors & Collaborators

• Fred Hutchinson Cancer Center: lead
• Nektar Therapeutics: collaborator

Study Sites (1)

Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

Location

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse

Interventions

Cyclophosphamide; fludarabine; NKTR-255; X-Rays; Phantoms, Imaging; Spinal Puncture; Magnetic Resonance Spectroscopy; Biopsy

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Electromagnetic Radiation; Electromagnetic Phenomena; Magnetic Phenomena; Physical Phenomena; Radiation; Radiation, Ionizing; Equipment and Supplies; Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Diagnostic Techniques, Neurological; Punctures; Therapeutics; Surgical Procedures, Operative; Investigative Techniques; Spectrum Analysis; Chemistry Techniques, Analytical; Cytodiagnosis; Cytological Techniques; Diagnostic Techniques, Surgical

Study Officials

• Alexandre Hirayama

  Fred Hutch/University of Washington Cancer Consortium

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 28, 2022
• First Posted: May 3, 2022
• Study Start: December 8, 2022
• Primary Completion: September 4, 2025
• Study Completion (Estimated): September 4, 2026
• Last Updated: March 20, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)