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

NCT04136756 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: 18-255-02
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 13

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.

Conditions

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

Keywords

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

Outcome Measures

Primary Outcomes (6)

• Incidence of Treatment-Emergent Adverse Events and Serious Adverse Events of NKTR-255 as a single agent

  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

  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

  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

  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

  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

  Through study completion, an expected average of 1 year

Study Arms (4)

Dose Escalation

EXPERIMENTAL

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; Drug: Rituximab; Drug: Daratumumab

Dose Expansion Cohort A

EXPERIMENTAL

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

Drug: NKTR-255

Dose Expansion Cohort B

EXPERIMENTAL

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

Drug: NKTR-255; Drug: Daratumumab

Dose Expansion Cohort C

EXPERIMENTAL

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

Drug: NKTR-255 Q21; Drug: Rituximab

Interventions

NKTR-255 DRUG

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

Dose Escalation; Dose Expansion Cohort A; Dose Expansion Cohort B

NKTR-255 Q21 DRUG

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

Dose Expansion Cohort C

Rituximab DRUG

Rituximab administered intravenously at specified dose on specified days

Also known as: RITUXAN(R)

Dose Escalation; Dose Expansion Cohort C

Daratumumab DRUG

Daratumumab administered subcutaneously at specified dose on specified days

Also known as: DARZALEX FASPRO(TM)

Dose Escalation; Dose Expansion Cohort B

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• Absolute neutrophil count (ANC) or absolute granulocyte count (AGC) ≥ 1000/µL
• Platelets ≥ 30,000/µL
• Hemoglobin ≥ 8g/dL
• Absolute lymphocytes ≥ 500/µL
• 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 :

You may not qualify if:

• 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.

Sponsors & Collaborators

• Nektar Therapeutics: lead

Study Sites (13)

Western Regional Medical Center - CTCA

Goodyear, Arizona, 85338, United States

Location

City of Hope

Duarte, California, 91010, United States

Location

University of California, San Francisco

San Francisco, California, 94143, United States

Location

H. Lee Moffitt Cancer Center and Research Institute

Tampa, Florida, 33612, United States

Location

Winship Cancer Institute, Emory University

Atlanta, Georgia, 30322, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

New York Medical College

Valhalla, New York, 10595, United States

Location

Duke University Health System

Durham, North Carolina, 27705, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Virginia Cancer Specialists

Fairfax, Virginia, 22031, United States

Location

University of Washington

Seattle, Washington, 98109, United States

Location

Related Publications (2)

• 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.

  PMID: 34154392 DERIVED

• 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.

  PMID: 34001523 DERIVED

MeSH Terms

Conditions

Multiple Myeloma; Lymphoma, Non-Hodgkin; Recurrence

Interventions

NKTR-255; Rituximab; daratumumab

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Lymphoma; Lymphatic Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Study Director

  Nektar Therapeutics

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 9, 2019
• First Posted: October 23, 2019
• Study Start: October 7, 2019
• Primary Completion: April 24, 2023
• Study Completion: April 24, 2023
• Last Updated: June 15, 2023

Record last verified: 2023-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (13)