Clinical Trials /

NKTR-255 in Relapsed/Refractory Multiple Myeloma & Non Hodgkin Lymphoma & Combined With Daratumumab for Multiple Myeloma

NCT04136756

Description:

Patients will receive intravenous 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, approximately 18 Multiple Myeloma (MM) or non-Hodgkin lymphoma (NHL) patients who may have received a chimeric antigen receptor T-cell (CAR-T) product and had progressive disease (PD) will receive NKTR-255 and approximately 18 MM patients who previously received daratumumab or other anti-CD38 therapies will receive NKTR-255 and daratumumab. Phase 1 study to evaluate safety and tolerability of NKTR-255 along and in combination with daratumumab in subjects with relapsed/refractory NHL and multiple myeloma.

Related Conditions:
  • 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 & Combined With Daratumumab for Multiple Myeloma
  • 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 and in Combination With Daratumumab as a Salvage Regimen for Multiple Myeloma

Clinical Trial IDs

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

Conditions

  • Multiple Myeloma
  • Non Hodgkin Lymphoma

Interventions

DrugSynonymsArms
NKTR-255Dose Escalation of NKTR-255
DaratumumabDarzalexDose Expansion of NKTR-255 alone and with Daratumumab

Purpose

Patients will receive intravenous 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, approximately 18 Multiple Myeloma (MM) or non-Hodgkin lymphoma (NHL) patients who may have received a chimeric antigen receptor T-cell (CAR-T) product and had progressive disease (PD) will receive NKTR-255 and approximately 18 MM patients who previously received daratumumab or other anti-CD38 therapies will receive NKTR-255 and daratumumab. Phase 1 study to evaluate safety and tolerability of NKTR-255 along and in combination with daratumumab in subjects with relapsed/refractory NHL and multiple myeloma.

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 daratumumab. 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.

      The NKTR-255 starting dose in Dose Group 1 will be 1.5 µg/kg. Patients will receive
      intravenous (IV) NKTR-255 in 21-day cycles, starting on Cycle 1 Day 1.
    

Trial Arms

NameTypeDescriptionInterventions
Dose Escalation of NKTR-255ExperimentalThe NKTR-255 starting dose will be 1.5 µg/kg. Patients will receive intravenous (IV) NKTR-255 every 21 days (q21d) to establish RP2D.
  • NKTR-255
Dose Expansion of NKTR-255 alone and with DaratumumabExperimentalThe selected RP2D of NKTR-255 will be evaluated in 2 expansion Cohorts (A and B). Cohort A will expand NKTR-255 in patients with relapsed MM or NHL as a salvage regimen to further characterize safety and tolerability. Cohort B will combine NKTR-255 with daratumumab in patients with MM with progressive disease who have had at least 3 prior lines of therapy treatment may continue if there is clinical benefit as determined by the Investigator.
  • NKTR-255
  • Daratumumab

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.

          -  No active central nervous system (CNS) involvement with NHL.

          -  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 ≥ 800/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 may have 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.

          -  Patients with MM may have received a B cell maturation antigen (BCMA) 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 6 months washout

        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.

          -  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 6
             months washout

          -  Patients who have had < 28 days since the last anti-cancer treatment, chemotherapy,
             biological therapy, or < 14 days from approved tyrosine kinase inhibitor therapy
             (sunitinib, sorafenib, vemurafenib, dabrafenib, cobimetinib), 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)
      
Maximum Eligible Age:75 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
  • interleukin-15 (IL-15)
  • MM
  • NHL

Last Updated

October 21, 2019