NKTR-255 vs Placebo Following CD19-directed CAR-T Therapy in Patients With Relapsed/Refractory Large B-cell Lymphoma

NCT05664217 | Terminated Phase 2 DMC FDA Drug

• 1 other identifier: 18-255-01
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 22

Brief Summary

This study will evaluate the safety and efficacy of NKTR-255 following CD19-directed chimeric antigen (CAR)-T cell therapy in patients with relapsed or refractory (R/R) large B-cell lymphoma (LBCL). 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. Chimeric antigen (CAR)-T cell product 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 following the treatment with CD19 CAR-T cell therapy may work better in treating large B-cell lymphoma than either drug alone.

Conditions

Non-Hodgkin Lymphoma; Relapsed/Refractory Diffuse Large B-cell Lymphoma

Keywords

NHL; LBCL; DLBCL; CAR; CAR-T; cell therapy; NKTR-255; chimeric antigen receptor; autologous T-cell; axi-cel; liso-cel; immunotherapy; B-cell malignancies

Outcome Measures

Primary Outcomes (2)

• Complete response (CR) rate at month 6

  The incidence of complete response by the Lugano Classification (Cheson et al, 2014) as determined by blinded independent central review (BICR)

  At month 6 after the first infusion with study drug

• Event-free survival (EFS)

  Event-free survival is defined as the time from randomization to the earliest date of disease progression by the Lugano Classification (Cheson et al, 2014) as determined by BICR, commencement of new lymphoma therapy, or death from any cause.

  Up to 3 years after the first infusion with study drug

Secondary Outcomes (9)

• Incidence of treatment-emergent adverse events (AEs) and laboratory abnormalities by type and severity.

  From the first dose of study drug up to 30 days after the last dose of study drug

• Complete response (CR) rate at month 3

  At month 3 after the first infusion with study drug

• Best overall Complete response (CR) rate

  Up to 3 years

• Objective response rate (ORR) at month 3

  At month 3 after the first infusion with study drug

• Objective response rate (ORR) at month 6

  At month 6 after the first infusion with study drug

Study Arms (4)

Stage 1 NKTR-255 at 1.5 µg/kg

EXPERIMENTAL

In this arm of Stage 1 (Phase 2 of the study), NKTR-255 will be dosed at 1.5 µg/kg. NKTR-255 will be administered intravenously approximately 14 days after CD19-directed CAR-T cell infusion. Patients will be dosed every 3 weeks for up to 7 cycles or 5 months, whichever is earlier, in the absence of disease progression or unacceptable toxicity. The dose regimen for Stage 2 (Phase 3 of the study) will be selected based on the results of Stage 1 as reviewed by the Data Monitoring Committee (DMC) and the study team.

Drug: NKTR-255 at 1.5 µg/kg

Stage 1 NKTR-255 at 3.0 μg/kg

EXPERIMENTAL

In this arm of Stage 1 (Phase 2 of the study), NKTR-255 will be dosed at 3.0 μg/kg. NKTR-255 will be administered intravenously approximately 14 days after CD19-directed CAR-T cell infusion. Patients will be dosed every 3 weeks for up to 7 cycles or 5 months, whichever is earlier, in the absence of disease progression or unacceptable toxicity. The dose regimen for Stage 2 (Phase 3 of the study) will be selected based on the results of Stage 1 as reviewed by the Data Monitoring Committee (DMC) and the study team.

Drug: NKTR-255 at 3.0 μg/kg

Stage 1 NKTR-255 at 3.0/6.0 μg/kg

EXPERIMENTAL

In this arm of Stage 1 (Phase 2 of the study), patients will be dosed with 3.0 μg/kg NKTR-255 in Cycle 1 (C1) and continue in Cycle 2 and subsequent cycles (C+) with 6.0 μg/kg NKTR-255 (hereinafter referred to as 3.0/6.0 µg/kg NKTR-255). NKTR-255 will be administered intravenously approximately 14 days after CD19-directed CAR-T cell infusion. Patients will be dosed every 3 weeks for up to 7 cycles or 5 months, whichever is earlier, in the absence of disease progression or unacceptable toxicity. The dose regimen for Stage 2 (Phase 3 of the study) will be selected based on the results of Stage 1 as reviewed by the Data Monitoring Committee (DMC) and the study team.

Drug: NKTR-255 at 3.0/6.0 μg/kg

Placebo

PLACEBO COMPARATOR

Placebo is commercially available 0.9% Sodium Chloride Solution for Injection (USP). Placebo will be administered intravenously approximately 14 days after CD19-directed CAR-T cell infusion. Placebo will be infused every 3 weeks for up to 7 cycles or 5 months, whichever is earlier.

Other: Placebo Comparator

Interventions

NKTR-255 at 1.5 µg/kg DRUG

NKTR-255 at 1.5 µg/kg

Also known as: Polymer-conjugated interleukin (IL)-15 Receptor Agonist

Stage 1 NKTR-255 at 1.5 µg/kg

NKTR-255 at 3.0 μg/kg DRUG

NKTR-255 at 3.0 μg/kg

Also known as: Polymer-conjugated interleukin (IL)-15 Receptor Agonist

Stage 1 NKTR-255 at 3.0 μg/kg

NKTR-255 at 3.0/6.0 μg/kg DRUG

NKTR-255 at 3.0/6.0 μg/kg

Also known as: Polymer-conjugated interleukin (IL)-15 Receptor Agonist

Stage 1 NKTR-255 at 3.0/6.0 μg/kg

Placebo Comparator OTHER

Commercially available 0.9% Sodium Chloride Solution for Injection (USP)

Placebo

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.
• Received standard of care therapy with axi-cel or liso-cel (Stage 1 and Stage 2), or tisa-cel (Stage 2 only), for the respective FDA (or Summary of Product Characteristics \[SmPC\]) approved indication(s):
• liso-cel: Patients with LBCL (including diffuse LBCL \[DLBCL\] not otherwise specified \[including DLBCL arising from indolent lymphoma\], high-grade B-cell lymphoma, primary mediastinal LBCL, and follicular lymphoma Grade 3B), who have:
• refractory disease to first-line chemoimmunotherapy or relapse within 12 months of first-line chemoimmunotherapy;
• refractory disease to first-line chemoimmunotherapy or relapse after first-line chemoimmunotherapy and are not eligible for hematopoietic stem cell transplantation (HSCT) due to comorbidities or age; or,
• relapsed or refractory disease after two or more lines of systemic therapy.
• axi-cel: For the treatment of adult patients with LBCL that is:
• refractory to first-line chemoimmunotherapy;
• relapses within 12 months of first-line chemoimmunotherapy; or
• R/R LBCL after 2 lines of systemic therapy, including DLBCL not otherwise specified, primary mediastinal LBLC, high grade B-cell lymphoma, and DLBCL arising from follicular lymphoma.
• tisa-cel (Stage 2 only): Adult patients with R/R LBLC after two lines of systemic therapy including DLBCL not otherwise specified, high grade B-cell lymphoma and DLBCL arising from follicular lymphoma.
• Received lymphodepleting chemotherapy regimen according to the respective FDA (or SmPC) label for CAR-T cell therapy.
• Fluorodeoxyglucose (FDG)-avid disease on positron emission tomography (PET) imaging within 30 days prior to CAR-T cell infusion.
• FDG avid lesion(s) on PET/computed tomography (CT) scan following bridging therapy and prior to lymphodepletion, where applicable.
• Evidence of CD19 expression on any prior or current NHL tumor specimen or a high likelihood of CD19 expression based on disease histology per investigator's assessment.

You may not qualify if:

• Use of therapeutic doses of corticosteroids (≥ 5 mg/day prednisone or equivalent) or other systemic immunosuppression within 7 days prior to leukapheresis or within 72 hours prior to CAR-T cell infusion. Topical and/or inhaled steroids are permitted.
• For allogeneic hematopoietic cell transplant recipients, active graft versus host disease (GVHD) and/or systemic GVHD therapy during screening or up to 30 days prior to leukapheresis.
• Known active hepatitis B (detectable hepatitis B DNA) or hepatitis C (detectable hepatitis C 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 \[eg, ulcerative colitis, Crohn's disease\], 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.) within 1 year prior to randomization. The following are exceptions to this criterion:
• Vitiligo
• Alopecia
• Hypothyroidism (eg, 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 Investigator and with Medical Monitor approval
• History of any one of the following cardiovascular conditions within the 6 months prior to randomization: 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 Investigator or designee, is a contraindication to study treatment is also excluded.
• History or presence of clinically relevant central nervous system (CNS) pathology, such as epilepsy, seizure, paresis, aphasia, stroke, severe brain injuries, dementia, Parkinson's disease, cerebellar disease, or psychosis that in the opinion of the Investigator is a contraindication to study treatment.

Sponsors & Collaborators

• Nektar Therapeutics: lead

Study Sites (22)

University of California San Diego

La Jolla, California, 92093, United States

Location

Mayo Clinic Jacksonville

Jacksonville, Florida, 32224, United States

Location

Winship Cancer Institute of Emory University

Atlanta, Georgia, 30322, United States

Location

University of Chicago Medical Center

Chicago, Illinois, 60637, United States

Location

University Of Iowa Hospitals & Clinics

Iowa City, Iowa, 52242, United States

Location

University of Kansas Cancer Center

Fairway, Kansas, 66205, United States

Location

University of Maryland

Baltimore, Maryland, 21201, United States

Location

UMass Memorial Medical Center

Worcester, Massachusetts, 01655, United States

Location

Saint Louis University

St Louis, Missouri, 63110, United States

Location

Washington University School of Medicine in St. Louis

St Louis, Missouri, 63110, United States

Location

Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

NYU Langone Medical Center

New York, New York, 10016, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Novant Health Cancer Institute

Charlotte, North Carolina, 28204, United States

Location

Novant Health Cancer Institute - Winston-Salem

Winston-Salem, North Carolina, 27103, United States

Location

Oncology Hematology Care Inc - Cincinnati

Cincinnati, Ohio, 45236, United States

Location

Penn State Health Milton S. Hershey Medical Center

Hershey, Pennsylvania, 17033, United States

Location

Allegheny Health Network

Pittsburgh, Pennsylvania, 15224, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Intermountain Healthcare

Salt Lake City, Utah, 84143, United States

Location

Fred Hutchinson/University of Washington

Seattle, Washington, 98109, United States

Location

MeSH Terms

Conditions

Lymphoma, Non-Hodgkin; Lymphoma, Large B-Cell, Diffuse

Condition Hierarchy (Ancestors)

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

Study Officials

• Study Director

  Nektar Therapeutics

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: This is a double-blinded study. The Investigator, the patients, and all study site and Nektar personnel involved in study activities, other than those involved in dispensing the study drugs, conducting PK, PD sample analyses, and personnel supporting unblinded monitoring for drug accountability, must remain blinded to each patient's treatment assignment.
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: The study is conducted in two stages, with routine safety monitoring being conducted by the Data Monitoring Committee (DMC) on a regular basis. An enrollment pause will be implemented at the end of Stage 1, and the DMC will review safety and efficacy data from all available cohorts to make go/no-go and dose selection recommendations for Stage 2. The study team will be unblinded at the end of Stage 1 to review totality of the data including efficacy, safety, PK, and PD data.

Study Record Dates

• First Submitted: December 1, 2022
• First Posted: December 23, 2022
• Study Start: December 23, 2022
• Primary Completion: May 22, 2024
• Study Completion: August 16, 2024
• Last Updated: February 13, 2025

Record last verified: 2025-02

Locations

US (22)