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NKTR-255 in Relapsed/Refractory Multiple Myeloma & Non-Hodgkin Lymphoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04136756
Recruitment Status : Enrolling by invitation
First Posted : October 23, 2019
Last Update Posted : September 14, 2022
Sponsor:
Information provided by (Responsible Party):
Nektar Therapeutics

Study Description
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Brief Summary:

Patients will receive intravenous (IV) NKTR-255 in 21 or 28 day treatment cycles. During the Part 1 dose escalation portion of the trial, patients will either receive NKTR-255 as monotherapy, NKTR-255 administered as a doublet with daratumumab subcutaneous (DARZALEX FASPRO TM), or NKTR-255 administered as a doublet with rituximab. After determination of the recommended Phase 2 dose (RP2D) of NKTR-255, NKTR-255 will be evaluated in Part 2. During the Part 2 dose expansion portion of the trial, patients will either receive NKTR-255 as monotherapy, NKTR-255 administered as a doublet with daratumumab subcutaneous (DARZALEX FASPRO TM), or NKTR-255 administered as a doublet with rituximab.

This is a Phase 1 study to evaluate safety and tolerability of NKTR-255 alone and in combination with daratumumab or rituximab.


Condition or disease Intervention/treatment Phase
Multiple Myeloma Non-Hodgkin Lymphoma Indolent Non-Hodgkin Lymphoma Drug: NKTR-255 Drug: NKTR-255 Q21 Drug: Rituximab Drug: Daratumumab Phase 1

Detailed Description:

NKTR-255 is a cytokine that is designed to regulate T and natural killer cell activation, proliferation and promote their anti-tumor effects.

This is a Phase 1, open-label, multi-center, dose escalation, dose expansion, safety follow-up, and survival follow-up of NKTR-255 as a single agent and NKTR-255 in combination with DARZALEX FASPRO TM or rituximab. Study treatment is defined as any investigational treatment(s) or marketed product(s), intended to be administered to a study patient according to the study enrollment.

Part 1 will enroll relapsed/refractory multiple myeloma (MM) and Non-Hodgkin's Lymphoma (NHL) patients. In Part 2, Cohort A will enroll NHL patients who have progressed on a chimeric antigen receptor T-cell (CAR-T) product, Cohort B will enroll MM patients who previously received daratumumab and other anti-CD38 therapies to receive NKTR-255 alone and/or in combination with daratumumab, and Cohort C will enroll indolent Non-Hodgkin's Lymphoma (iNHL) patients who previously received rituximab and other therapies to receive NKTR-255 alone and/or in combination with rituximab.

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 118 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1, Open-label, Multi-center, Dose Escalation and Dose Expansion Study of NKTR-255 in Relapsed or Refractory Hematological Malignancies
Actual Study Start Date : October 7, 2019
Estimated Primary Completion Date : March 2023
Estimated Study Completion Date : October 2023

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: Dose Escalation

Evaluation of NKTR-255 as:

  • Monotherapy
  • In combination with daratumumab
  • In combination with rituximab

This phase will help to determine the RP2D of NKTR-255

 Drug: NKTR-255
NKTR-255 administered by IV infusion every 21 or 28 days to establish safety and tolerability

Drug: Rituximab
Rituximab administered intravenously at specified dose on specified days
Other Name: RITUXAN(R)

Drug: Daratumumab
Daratumumab administered subcutaneously at specified dose on specified days
Other Name: DARZALEX FASPRO(TM)
Experimental: Dose Expansion Cohort A
Evaluation of RP2D of NKTR-255 as monotherapy in patients with NHL relapsed after CAR-T
 Drug: NKTR-255
NKTR-255 administered by IV infusion every 21 or 28 days to establish safety and tolerability
Experimental: Dose Expansion Cohort B
Evaluation of RP2D of NKTR-255 as monotherapy and in combination with SC daratumumab in patients with R/R MM
 Drug: NKTR-255
NKTR-255 administered by IV infusion every 21 or 28 days to establish safety and tolerability

Drug: Daratumumab
Daratumumab administered subcutaneously at specified dose on specified days
Other Name: DARZALEX FASPRO(TM)
Experimental: Dose Expansion Cohort C
Evaluation of RP2D of NKTR-255 as monotherapy and in combination with rituximab in patients with R/R iNHL
 Drug: NKTR-255 Q21
NKTR-255 administered by IV infusion every 21 days to establish safety and tolerability

Drug: Rituximab
Rituximab administered intravenously at specified dose on specified days
Other Name: RITUXAN(R)


Outcome Measures
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Primary Outcome Measures :
  1. Incidence of Treatment-Emergent Adverse Events and Serious Adverse Events of NKTR-255 as a single agent [ Time Frame: Through study completion, an expected average of 6 months ]
    Safety and tolerability of NKTR-255 as evaluated by incidence of Dose Limiting Toxicities (DLTs), drug-related Adverse Events (AEs), Serious Adverse Events (SAEs), AEs leading to discontinuation, deaths, clinical laboratory abnormalities per CTCAE v5.

  2. Incidence of Treatment-Emergent Adverse Events and Serious Adverse Events of NKTR-255 with daratumumab SC [ Time Frame: Through study completion, an expected average of 1 year ]
    Safety and tolerability of NKTR-255 in combination with daratumumab as evaluated by incidence of drug-related AEs, SAEs, AEs leading to discontinuation, deaths, clinical laboratory abnormalities per CTCAE v5

  3. Incidence of Treatment-Emergent Adverse Events and Serious Adverse Events of NKTR-255 with rituximab [ Time Frame: Through study completion, an expected average of 1 year ]
    Safety and tolerability of NKTR-255 in combination with rituximab as evaluated by incidence of drug-related AEs, SAEs, AEs leading to discontinuation, deaths, clinical laboratory abnormalities per CTCAE v5

  4. Evaluate the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of NKTR-255 as a single agent [ Time Frame: Through study completion, an expected average of 6 months ]
  5. Evaluate the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of NKTR-255 in combination with daratumumab SC [ Time Frame: Through study completion, an expected average of 1 year ]
  6. Evaluate the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of NKTR-255 in combination with rituximab [ Time Frame: Through study completion, an expected average of 1 year ]

Eligibility Criteria
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Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Key Inclusion Criteria:

  • Patients must have relapsed or refractory MM or NHL with no available therapies that would confer clinical benefit for their primary disease.
  • For MM patients, measurable relapsed or refractory MM as defined by the IMWG Criteria (Kumar, 2016) following treatment with at least 3 lines of therapy with no other available treatment that would confer benefit.
  • For NHL patients, measurable or detectable disease according to International Myeloma Working Group (IMWG) and the Lugano Classification. Extranodal NHL disease that is measurable by fluorodeoxyglucose-positron emission tomography (FDG-PET) imaging only is allowed.
  • Estimated glomerular filtration rate (eGFR) ≥ 40 mL/min/1.73 m2.
  • Eastern Cooperative Oncology Group (ECOG) performance status score ≤ 2

Patient has the following laboratory test results during Screening:

  1. Absolute neutrophil count (ANC) or absolute granulocyte count (AGC) ≥ 1000/µL
  2. Platelets ≥ 30,000/µL
  3. Hemoglobin ≥ 8g/dL
  4. Absolute lymphocytes ≥ 500/µL
  5. Leukocytes ≥ 3000/µL

Patients are eligible who also meet all the following criteria in these cohorts of Part 2:

NKTR-255 Monotherapy NHL Group Only:

  • Patients with NHL who received a commercially approved CD19 CAR-T product and had PD. The first dose of NKTR-255 will be administered within 30 days of the PD.

NKTR-255 with Daratumumab MM Group Only :

  • Patients with MM must have had previous exposure to proteasome inhibitor, immunomodulatory agent (IMiD), and anti-CD38 therapy.
  • Patients who previously received daratumumab or other anti-CD38 therapies must have at least 3 months washout.

NKTR-255 with Rituximab Group iNHL Group Only:

  • Patients with relapsed or refractory iNHL who previously progressed during or following 1 or more prior systemic rituximab-containing (or another treatment with an anti-CD20 antibody-containing) regimens for lymphoma.

Key Exclusion Criteria:

  • Patients who have an active, known, or suspected autoimmune disease.
  • Any treatment-related neurotoxicity or cytokine release syndrome (CRS) prior to enrollment into the study should return to baseline before NKTR-255 treatment.
  • Active central nervous system (CNS) involvement with NHL.
  • Patients who have been previously treated with prior interleukin-2 or interleukin-15.
  • Patients who received daratumumab or other anti-CD38 therapies previously must have 3 months washout.

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply

Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04136756


Locations
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United States, Arizona
Western Regional Medical Center - CTCA
Goodyear, Arizona, United States, 85338
United States, California
City of Hope
Duarte, California, United States, 91010
University of California, San Francisco
San Francisco, California, United States, 94143
United States, Florida
H. Lee Moffitt Cancer Center and Research Institute
Tampa, Florida, United States, 33612
United States, Georgia
Winship Cancer Institute, Emory University
Atlanta, Georgia, United States, 30322
United States, Michigan
University of Michigan
Ann Arbor, Michigan, United States, 48109
United States, Minnesota
University of Minnesota
Minneapolis, Minnesota, United States, 55455
United States, New York
Memorial Sloan Kettering Cancer Center
New York, New York, United States, 10065
New York Medical College
Valhalla, New York, United States, 10595
United States, North Carolina
Duke University Health System
Durham, North Carolina, United States, 27705
United States, Texas
MD Anderson Cancer Center
Houston, Texas, United States, 77030
United States, Virginia
Virginia Cancer Specialists
Fairfax, Virginia, United States, 22031
United States, Washington
University of Washington
Seattle, Washington, United States, 98109
Sponsors and Collaborators
Nektar Therapeutics
Investigators
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Study Director: Study Director Nektar Therapeutics
More Information
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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: Nektar Therapeutics
ClinicalTrials.gov Identifier: NCT04136756    
Other Study ID Numbers: 18-255-02
First Posted: October 23, 2019    Key Record Dates
Last Update Posted: September 14, 2022
Last Verified: September 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Nektar Therapeutics:
NKTR-255
relapsed
refractory
CAR-T
daratumumab subcutaneous (sc)
interleukin-15 (IL-15)
 MM
NHL
indolent
rituximab
Truxima®
Additional relevant MeSH terms:
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Lymphoma
Multiple Myeloma
Neoplasms, Plasma Cell
Lymphoma, Non-Hodgkin
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Hemostatic Disorders
Vascular Diseases
 Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Rituximab
Daratumumab
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents