Clinical Trials /

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

NCT04136756

Description:

Patients will receive intravenous (IV) NKTR-255 in 21-day treatment cycles. During the Part 1 dose escalation portion of the trial, NKTR-255 will be given as monotherapy. After determination of the recommended Phase 2 dose (RP2D) of NKTR-255, NKTR-255 will be evaluated in 3 expansion Cohorts in Part 2 with daratumumab subcutaneous (DARZALEX FASPRO TM) and rituximab. Cohort A will enroll Non-Hodgkin Lymphoma (NHL) patients that have relapsed after CAR-T therapy. Cohort B will enroll patients with relapsed/refractory Multiple Myeloma (MM). Cohort C will enroll patients with relapsed/refractory indolent Non-Hodgkin Lymphoma (iNHL). This is a Phase 1 study to evaluate safety and tolerability of NKTR-255 alone and in combination with daratumumab or rituximab.

Related Conditions:
  • Indolent Non-Hodgkin Lymphoma
  • Multiple Myeloma
  • Non-Hodgkin Lymphoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • 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 as a Single Agent in Relapsed or Refractory Hematological Malignancies

Clinical Trial IDs

  • ORG STUDY ID: 18-255-02
  • NCT ID: NCT04136756

Conditions

  • Multiple Myeloma
  • Non-Hodgkin Lymphoma
  • Indolent Non-Hodgkin Lymphoma

Interventions

DrugSynonymsArms
NKTR-255Dose Escalation of NKTR-255
DaratumumabDARZALEX FASPRO(TM)Dose Expansion of NKTR-255 with Daratumumab
RituximabRITUXAN(R)Dose Expansion of NKTR-255 with Rituximab

Purpose

Patients will receive intravenous (IV) NKTR-255 in 21-day treatment cycles. During the Part 1 dose escalation portion of the trial, NKTR-255 will be given as monotherapy. After determination of the recommended Phase 2 dose (RP2D) of NKTR-255, NKTR-255 will be evaluated in 3 expansion Cohorts in Part 2 with daratumumab subcutaneous (DARZALEX FASPRO TM) and rituximab. Cohort A will enroll Non-Hodgkin Lymphoma (NHL) patients that have relapsed after CAR-T therapy. Cohort B will enroll patients with relapsed/refractory Multiple Myeloma (MM). Cohort C will enroll patients with relapsed/refractory indolent Non-Hodgkin Lymphoma (iNHL). 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 MM and 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 iNHL patients who previously received rituximab and other therapies to receive
      NKTR-255 alone and/or in combination with rituximab.
    

Trial Arms

NameTypeDescriptionInterventions
Dose Escalation of NKTR-255ExperimentalPatients will receive IV infusion of NKTR-255 every 21 or 28 days to establish RP2D.
  • NKTR-255
Dose Expansion of NKTR-255 aloneExperimentalThe selected RP2D of NKTR-255 will be evaluated in expansion cohorts. Cohort A in patients with relapsed NHL after CAR-T therapy as a salvage regimen to further characterize safety and tolerability. Cohort B1 will evaluate NKTR-255 in patients with MM with progressive disease who have had at least 3 prior lines of therapy treatment. Cohort C1 will evaluate patients with iNHL that has progressed during or following 1 or more prior systemic rituximab-containing (or another treatment with an anti-CD20 antibody-containing) regimens for lymphoma.
  • NKTR-255
Dose Expansion of NKTR-255 with DaratumumabExperimentalThe selected RP2D of NKTR-255 will be evaluated in expansion Cohort B2, which will combine NKTR-255 with daratumumab in patients with MM with progressive disease who have had at least 3 prior lines of therapy treatment.
  • NKTR-255
  • Daratumumab
Dose Expansion of NKTR-255 with RituximabExperimentalThe selected RP2D of NKTR-255 will be evaluated in Cohort C2, which will combine NKTR-255 with rituximab in patients with iNHL that has progressed during or following 1 or more prior systemic rituximab-containing (or another treatment with an anti-CD20 antibody-containing) regimens for lymphoma.
  • NKTR-255
  • Rituximab

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.

          -  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.

        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:

        Cohort A 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.

        Cohort B 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.

        Cohort C 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.

          -  Patients who have had < 28 days since the last anti-cancer treatment, chemotherapy,
             biological therapy, or < 14 days from approved anti-myeloma agents, or systemic or
             inhaled steroid therapy at doses greater than 10 mg of prednisone or equivalent before
             administration of the first dose of study drug(s).

          -  Prolonged Fridericia's corrected QT interval (QTcF) > 450 ms for men and > 470 ms for
             women at Screening.

          -  Contraindication to or unable to receive daratumumab (Cohort B only)

        NOTE: Other protocol defined Inclusion/Exclusion criteria may apply
      
Maximum Eligible Age:80 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence of Treatment-Emergent Adverse Events and Serious Adverse Events of NKTR-255
Time Frame:Through study completion, an expected average of 6 months
Safety Issue:
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.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Nektar Therapeutics

Trial Keywords

  • relapsed
  • refractory
  • NKTR-255
  • CAR-T
  • daratumumab subcutaneous (sc)
  • interleukin-15 (IL-15)
  • MM
  • NHL
  • indolent
  • rituximab

Last Updated

April 19, 2021