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

June 13, 2023 updated by: Nektar Therapeutics

A Phase 1, Open-label, Multi-center, Dose Escalation and Dose Expansion Study of NKTR-255 in Relapsed or Refractory Hematological Malignancies

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

30

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Arizona
      • Goodyear, Arizona, United States, 85338
        • Western Regional Medical Center - CTCA
    • California
      • Duarte, California, United States, 91010
        • City of Hope
      • San Francisco, California, United States, 94143
        • University of California, San Francisco
    • Florida
      • Tampa, Florida, United States, 33612
        • H. Lee Moffitt Cancer Center and Research Institute
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Winship Cancer Institute, Emory University
    • Michigan
      • Ann Arbor, Michigan, United States, 48109
        • University of Michigan
    • Minnesota
      • Minneapolis, Minnesota, United States, 55455
        • University of Minnesota
    • New York
      • New York, New York, United States, 10065
        • Memorial Sloan Kettering Cancer Center
      • Valhalla, New York, United States, 10595
        • New York Medical College
    • North Carolina
      • Durham, North Carolina, United States, 27705
        • Duke University Health System
    • Texas
      • Houston, Texas, United States, 77030
        • MD Anderson Cancer Center
    • Virginia
      • Fairfax, Virginia, United States, 22031
        • Virginia Cancer Specialists
    • Washington
      • Seattle, Washington, United States, 98109
        • University of Washington

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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 Names:
  • RITUXAN(R)
Drug: Daratumumab
Daratumumab administered subcutaneously at specified dose on specified days
Other Names:
  • 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 Names:
  • 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: Rituximab
Rituximab administered intravenously at specified dose on specified days
Other Names:
  • RITUXAN(R)
Drug: NKTR-255 Q21
NKTR-255 administered by IV infusion every 21 days to establish safety and tolerability

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Through study completion, an expected average of 6 months
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
Through study completion, an expected average of 1 year
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
Through study completion, an expected average of 1 year
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
Through study completion, an expected average of 6 months
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
Through study completion, an expected average of 1 year
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
Through study completion, an expected average of 1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Nektar Therapeutics

Investigators

  • Study Director: Study Director, Nektar Therapeutics

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 7, 2019

Primary Completion (Actual)

April 24, 2023

Study Completion (Actual)

April 24, 2023

Study Registration Dates

First Submitted

October 9, 2019

First Submitted That Met QC Criteria

October 21, 2019

First Posted (Actual)

October 23, 2019

Study Record Updates

Last Update Posted (Actual)

June 15, 2023

Last Update Submitted That Met QC Criteria

June 13, 2023

Last Verified

June 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 18-255-02

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Multiple Myeloma

Clinical Trials on NKTR-255

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Lithuania

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe