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

Primary Purpose

Multiple Myeloma, Non-Hodgkin Lymphoma, Indolent Non-Hodgkin Lymphoma

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
NKTR-255
NKTR-255 Q21
Rituximab
Daratumumab
Sponsored by
Nektar Therapeutics
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Multiple Myeloma focused on measuring relapsed, refractory, NKTR-255, CAR-T, daratumumab subcutaneous (sc), interleukin-15 (IL-15), MM, NHL, indolent, rituximab, Truxima®

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Western Regional Medical Center - CTCA
  • City of Hope
  • University of California, San Francisco
  • H. Lee Moffitt Cancer Center and Research Institute
  • Winship Cancer Institute, Emory University
  • University of Michigan
  • University of Minnesota
  • Memorial Sloan Kettering Cancer Center
  • New York Medical College
  • Duke University Health System
  • MD Anderson Cancer Center
  • Virginia Cancer Specialists
  • University of Washington

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Experimental

Arm Label

Dose Escalation

Dose Expansion Cohort A

Dose Expansion Cohort B

Dose Expansion Cohort C

Arm Description

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

Evaluation of RP2D of NKTR-255 as monotherapy in patients with NHL relapsed after CAR-T

Evaluation of RP2D of NKTR-255 as monotherapy and in combination with SC daratumumab in patients with R/R MM

Evaluation of RP2D of NKTR-255 as monotherapy and in combination with rituximab in patients with R/R iNHL

Outcomes

Primary Outcome Measures

Incidence of Treatment-Emergent Adverse Events and Serious Adverse Events of NKTR-255 as a single agent
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.
Incidence of Treatment-Emergent Adverse Events and Serious Adverse Events of NKTR-255 with daratumumab SC
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
Incidence of Treatment-Emergent Adverse Events and Serious Adverse Events of NKTR-255 with rituximab
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
Evaluate the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of NKTR-255 as a single agent
Evaluate the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of NKTR-255 in combination with daratumumab SC
Evaluate the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of NKTR-255 in combination with rituximab

Secondary Outcome Measures

Full Information

First Posted
October 9, 2019
Last Updated
June 13, 2023
Sponsor
Nektar Therapeutics
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1. Study Identification

Unique Protocol Identification Number
NCT04136756
Brief Title
NKTR-255 in Relapsed/Refractory Multiple Myeloma & Non-Hodgkin Lymphoma
Official Title
A Phase 1, Open-label, Multi-center, Dose Escalation and Dose Expansion Study of NKTR-255 in Relapsed or Refractory Hematological Malignancies
Study Type
Interventional

2. Study Status

Record Verification Date
June 2023
Overall Recruitment Status
Completed
Study Start Date
October 7, 2019 (Actual)
Primary Completion Date
April 24, 2023 (Actual)
Study Completion Date
April 24, 2023 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Nektar Therapeutics

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Myeloma, Non-Hodgkin Lymphoma, Indolent Non-Hodgkin Lymphoma
Keywords
relapsed, refractory, NKTR-255, CAR-T, daratumumab subcutaneous (sc), interleukin-15 (IL-15), MM, NHL, indolent, rituximab, Truxima®

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
30 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Dose Escalation
Arm Type
Experimental
Arm Description
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
Arm Title
Dose Expansion Cohort A
Arm Type
Experimental
Arm Description
Evaluation of RP2D of NKTR-255 as monotherapy in patients with NHL relapsed after CAR-T
Arm Title
Dose Expansion Cohort B
Arm Type
Experimental
Arm Description
Evaluation of RP2D of NKTR-255 as monotherapy and in combination with SC daratumumab in patients with R/R MM
Arm Title
Dose Expansion Cohort C
Arm Type
Experimental
Arm Description
Evaluation of RP2D of NKTR-255 as monotherapy and in combination with rituximab in patients with R/R iNHL
Intervention Type
Drug
Intervention Name(s)
NKTR-255
Intervention Description
NKTR-255 administered by IV infusion every 21 or 28 days to establish safety and tolerability
Intervention Type
Drug
Intervention Name(s)
NKTR-255 Q21
Intervention Description
NKTR-255 administered by IV infusion every 21 days to establish safety and tolerability
Intervention Type
Drug
Intervention Name(s)
Rituximab
Other Intervention Name(s)
RITUXAN(R)
Intervention Description
Rituximab administered intravenously at specified dose on specified days
Intervention Type
Drug
Intervention Name(s)
Daratumumab
Other Intervention Name(s)
DARZALEX FASPRO(TM)
Intervention Description
Daratumumab administered subcutaneously at specified dose on specified days
Primary Outcome Measure Information:
Title
Incidence of Treatment-Emergent Adverse Events and Serious Adverse Events of NKTR-255 as a single agent
Description
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.
Time Frame
Through study completion, an expected average of 6 months
Title
Incidence of Treatment-Emergent Adverse Events and Serious Adverse Events of NKTR-255 with daratumumab SC
Description
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
Time Frame
Through study completion, an expected average of 1 year
Title
Incidence of Treatment-Emergent Adverse Events and Serious Adverse Events of NKTR-255 with rituximab
Description
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
Time Frame
Through study completion, an expected average of 1 year
Title
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
Title
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
Title
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility 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: Absolute neutrophil count (ANC) or absolute granulocyte count (AGC) ≥ 1000/µL Platelets ≥ 30,000/µL Hemoglobin ≥ 8g/dL Absolute lymphocytes ≥ 500/µL 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Study Director
Organizational Affiliation
Nektar Therapeutics
Official's Role
Study Director
Facility Information:
Facility Name
Western Regional Medical Center - CTCA
City
Goodyear
State/Province
Arizona
ZIP/Postal Code
85338
Country
United States
Facility Name
City of Hope
City
Duarte
State/Province
California
ZIP/Postal Code
91010
Country
United States
Facility Name
University of California, San Francisco
City
San Francisco
State/Province
California
ZIP/Postal Code
94143
Country
United States
Facility Name
H. Lee Moffitt Cancer Center and Research Institute
City
Tampa
State/Province
Florida
ZIP/Postal Code
33612
Country
United States
Facility Name
Winship Cancer Institute, Emory University
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Facility Name
University of Michigan
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
Country
United States
Facility Name
University of Minnesota
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55455
Country
United States
Facility Name
Memorial Sloan Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Facility Name
New York Medical College
City
Valhalla
State/Province
New York
ZIP/Postal Code
10595
Country
United States
Facility Name
Duke University Health System
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27705
Country
United States
Facility Name
MD Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Virginia Cancer Specialists
City
Fairfax
State/Province
Virginia
ZIP/Postal Code
22031
Country
United States
Facility Name
University of Washington
City
Seattle
State/Province
Washington
ZIP/Postal Code
98109
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
34154392
Citation
Shah N, Perales MA, Turtle CJ, Cairo MS, Cowan AJ, Saeed H, Budde LE, Tan A, Lee Z, Kai K, Marcondes MQ, Zalevsky J, Tagliaferri MA, Patel KK. Phase I study protocol: NKTR-255 as monotherapy or combined with daratumumab or rituximab in hematologic malignancies. Future Oncol. 2021 Sep;17(27):3549-3560. doi: 10.2217/fon-2021-0576. Epub 2021 Jun 22.
Results Reference
derived
PubMed Identifier
34001523
Citation
Miyazaki T, Maiti M, Hennessy M, Chang T, Kuo P, Addepalli M, Obalapur P, Sheibani S, Wilczek J, Pena R, Quach P, Cetz J, Moffett A, Tang Y, Kirk P, Huang J, Sheng D, Zhang P, Rubas W, Madakamutil L, Kivimae S, Zalevsky J. NKTR-255, a novel polymer-conjugated rhIL-15 with potent antitumor efficacy. J Immunother Cancer. 2021 May;9(5):e002024. doi: 10.1136/jitc-2020-002024.
Results Reference
derived

Learn more about this trial

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

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