Clinical trial NCT04136756: NKTR-255 in Relapsed/Refractory Multiple Myeloma & Non-Hodgkin Lymphoma
Official title: A Phase 1, Open-label, Multi-center, Dose Escalation and Dose Expansion Study of NKTR-255 in Relapsed or Refractory Hematological Malignancies
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
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®
Lead sponsor: Nektar Therapeutics
Sponsor class: INDUSTRY
First posted: 2019-10-23
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

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.
* 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

Primary outcomes:
measure: Incidence of Treatment-Emergent Adverse Events and Serious Adverse Events of NKTR-255 as a single agent
timeFrame: Through study completion, an expected average of 6 months
measure: Incidence of Treatment-Emergent Adverse Events and Serious Adverse Events of NKTR-255 with daratumumab SC
timeFrame: Through study completion, an expected average of 1 year
measure: Incidence of Treatment-Emergent Adverse Events and Serious Adverse Events of NKTR-255 with rituximab
timeFrame: Through study completion, an expected average of 1 year
measure: Evaluate the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of NKTR-255 as a single agent
timeFrame: Through study completion, an expected average of 6 months
measure: Evaluate the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of NKTR-255 in combination with daratumumab SC
timeFrame: Through study completion, an expected average of 1 year
measure: Evaluate the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of NKTR-255 in combination with rituximab
timeFrame: Through study completion, an expected average of 1 year
Secondary outcomes:
Other outcomes:
Locations:
city: Goodyear
country: United States
facility: Western Regional Medical Center - CTCA
state: Arizona
city: Duarte
country: United States
facility: City of Hope
state: California
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center and Research Institute
state: Florida
city: Atlanta
country: United States
facility: Winship Cancer Institute, Emory University
state: Georgia
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Valhalla
country: United States
facility: New York Medical College
state: New York
city: Durham
country: United States
facility: Duke University Health System
state: North Carolina
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Fairfax
country: United States
facility: Virginia Cancer Specialists
state: Virginia
city: Seattle
country: United States
facility: University of Washington
state: Washington
Study officials:
affiliation: Nektar Therapeutics
name: Study Director
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.