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

Multiple Myeloma Clinical Trial

Official title:

A Phase 1, Open-label, Multi-center, Dose Escalation and Dose Expansion Study of NKTR-255 in Relapsed or Refractory Hematological Malignancies

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04136756
• Other study ID #: 18-255-02
• Status: Completed
• Phase: Phase 1
• Start date: October 7, 2019
• Est. completion date: April 24, 2023

Study information

• Verified date: June 2023
• Source: Nektar Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: April 24, 2023
• Est. primary completion date: April 24, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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.
• 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.

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. NOTE: Other protocol defined Inclusion/Exclusion criteria may apply

Related Conditions & MeSH terms

• Indolent Non-Hodgkin Lymphoma
• Lymphoma
• Lymphoma, Non-Hodgkin
• Multiple Myeloma
• Neoplasms, Plasma Cell
• Non-Hodgkin Lymphoma

Intervention

Drug:
• NKTR-255
NKTR-255 administered by IV infusion every 21 or 28 days to establish safety and tolerability
• NKTR-255 Q21
NKTR-255 administered by IV infusion every 21 days to establish safety and tolerability
• Rituximab
Rituximab administered intravenously at specified dose on specified days
• Daratumumab
Daratumumab administered subcutaneously at specified dose on specified days

Locations

Country	Name	City	State
United States	University of Michigan	Ann Arbor	Michigan
United States	Winship Cancer Institute, Emory University	Atlanta	Georgia
United States	City of Hope	Duarte	California
United States	Duke University Health System	Durham	North Carolina
United States	Virginia Cancer Specialists	Fairfax	Virginia
United States	Western Regional Medical Center - CTCA	Goodyear	Arizona
United States	MD Anderson Cancer Center	Houston	Texas
United States	University of Minnesota	Minneapolis	Minnesota
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	University of California, San Francisco	San Francisco	California
United States	University of Washington	Seattle	Washington
United States	H. Lee Moffitt Cancer Center and Research Institute	Tampa	Florida
United States	New York Medical College	Valhalla	New York

Sponsors (1)

Lead Sponsor	Collaborator
Nektar Therapeutics

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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