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

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ClinicalTrials.gov Identifier: NCT04136756
Recruitment Status : Recruiting
First Posted : October 23, 2019
Last Update Posted : July 30, 2021
Sponsor:
Information provided by (Responsible Party):
Nektar Therapeutics

Tracking Information
First Submitted Date  ICMJE October 9, 2019
First Posted Date  ICMJE October 23, 2019
Last Update Posted Date July 30, 2021
Actual Study Start Date  ICMJE October 7, 2019
Estimated Primary Completion Date April 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 12, 2020)
  • 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 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 [ 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
  • 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
Original Primary Outcome Measures  ICMJE
 (submitted: October 21, 2019)
  • 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 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 [ 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
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE NKTR-255 in Relapsed/Refractory Multiple Myeloma & Non-Hodgkin Lymphoma
Official Title  ICMJE 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
Brief Summary

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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Multiple Myeloma
  • Non-Hodgkin Lymphoma
  • Indolent Non-Hodgkin Lymphoma
Intervention  ICMJE
  • 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)
  • Drug: Rituximab
    Rituximab administered intravenously at specified dose on specified days
    Other Name: RITUXAN(R)
Study Arms  ICMJE
  • Experimental: Dose Escalation of NKTR-255
    Patients will receive IV infusion of NKTR-255 every 21 or 28 days to establish RP2D.
    Intervention: Drug: NKTR-255
  • Experimental: Dose Expansion of NKTR-255 alone
    The 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.
    Intervention: Drug: NKTR-255
  • Experimental: Dose Expansion of NKTR-255 with Daratumumab
    The 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.
    Interventions:
    • Drug: NKTR-255
    • Drug: Daratumumab
  • Experimental: Dose Expansion of NKTR-255 with Rituximab
    The 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.
    Interventions:
    • Drug: NKTR-255
    • Drug: Rituximab
Publications * 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 Jun 22. doi: 10.2217/fon-2021-0576. [Epub ahead of print]

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: December 23, 2020)
118
Original Estimated Enrollment  ICMJE
 (submitted: October 21, 2019)
82
Estimated Study Completion Date  ICMJE September 2022
Estimated Primary Completion Date April 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 80 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Nektar Recruitment 855-482-8676 StudyInquiry@nektar.com
Contact: Medical Affairs 855-482-8676 medicalaffairs@nektar.com
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04136756
Other Study ID Numbers  ICMJE 18-255-02
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Nektar Therapeutics
Study Sponsor  ICMJE Nektar Therapeutics
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Study Director Nektar Therapeutics
PRS Account Nektar Therapeutics
Verification Date July 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP