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

NCT ID: NCT04136756

Last Updated: 2023-06-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-10-07
• Study Completion Date: 2023-04-24

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.

Conditions

Multiple Myeloma; Non-Hodgkin Lymphoma; Indolent Non-Hodgkin Lymphoma

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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

Group Type: EXPERIMENTAL

NKTR-255

Intervention Type: DRUG

NKTR-255 administered by IV infusion every 21 or 28 days to establish safety and tolerability

Rituximab

Intervention Type: DRUG

Rituximab administered intravenously at specified dose on specified days

Daratumumab

Intervention Type: DRUG

Daratumumab administered subcutaneously at specified dose on specified days

Dose Expansion Cohort A

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

Group Type: EXPERIMENTAL

NKTR-255

Intervention Type: DRUG

NKTR-255 administered by IV infusion every 21 or 28 days to establish safety and tolerability

Dose Expansion Cohort B

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

Group Type: EXPERIMENTAL

NKTR-255

Intervention Type: DRUG

NKTR-255 administered by IV infusion every 21 or 28 days to establish safety and tolerability

Daratumumab

Intervention Type: DRUG

Daratumumab administered subcutaneously at specified dose on specified days

Dose Expansion Cohort C

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

Group Type: EXPERIMENTAL

NKTR-255 Q21

Intervention Type: DRUG

NKTR-255 administered by IV infusion every 21 days to establish safety and tolerability

Rituximab

Intervention Type: DRUG

Rituximab administered intravenously at specified dose on specified days

Interventions

NKTR-255

NKTR-255 administered by IV infusion every 21 or 28 days to establish safety and tolerability

Intervention Type: DRUG

NKTR-255 Q21

NKTR-255 administered by IV infusion every 21 days to establish safety and tolerability

Intervention Type: DRUG

Rituximab

Rituximab administered intravenously at specified dose on specified days

Intervention Type: DRUG

Daratumumab

Daratumumab administered subcutaneously at specified dose on specified days

Intervention Type: DRUG

Other Intervention Names

RITUXAN(R); DARZALEX FASPRO(TM)

Eligibility Criteria

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.

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Nektar Therapeutics

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Study Director

Role: STUDY_DIRECTOR

Nektar Therapeutics

Locations

Western Regional Medical Center - CTCA

Goodyear, Arizona, United States

City of Hope

Duarte, California, United States

University of California, San Francisco

San Francisco, California, United States

H. Lee Moffitt Cancer Center and Research Institute

Tampa, Florida, United States

Winship Cancer Institute, Emory University

Atlanta, Georgia, United States

University of Michigan

Ann Arbor, Michigan, United States

University of Minnesota

Minneapolis, Minnesota, United States

Memorial Sloan Kettering Cancer Center

New York, New York, United States

New York Medical College

Valhalla, New York, United States

Duke University Health System

Durham, North Carolina, United States

MD Anderson Cancer Center

Houston, Texas, United States

Virginia Cancer Specialists

Fairfax, Virginia, United States

University of Washington

Seattle, Washington, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 34154392 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 34001523 (View on PubMed)

Other Identifiers

18-255-02

Identifier Type: -

Identifier Source: org_study_id