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

Sponsor

Nektar Therapeutics (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04136756

Collaborator

(none)

118

Enrollment

Locations

Arms

38.8

Anticipated Duration (Months)

6.9

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Multiple Myeloma Non-Hodgkin Lymphoma Indolent Non-Hodgkin Lymphoma	Drug: NKTR-255 Drug: NKTR-255 Q21 Drug: Rituximab Drug: Daratumumab	Phase 1

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

118 participants

Allocation:

Non-Randomized

Intervention Model:

Sequential Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Oct 7, 2019

Anticipated Primary Completion Date :

Jun 1, 2022

Anticipated Study Completion Date :

Jan 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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	Drug: NKTR-255 NKTR-255 administered by IV infusion every 21 or 28 days to establish safety and tolerability Drug: Rituximab Rituximab administered intravenously at specified dose on specified days Other Names: RITUXAN(R) Drug: Daratumumab Daratumumab administered subcutaneously at specified dose on specified days Other Names: DARZALEX FASPRO(TM)
Experimental: Dose Expansion Cohort A Evaluation of RP2D of NKTR-255 as monotherapy in patients with NHL relapsed after CAR-T	Drug: NKTR-255 NKTR-255 administered by IV infusion every 21 or 28 days to establish safety and tolerability
Experimental: Dose Expansion Cohort B Evaluation of RP2D of NKTR-255 as monotherapy and in combination with SC daratumumab in patients with R/R MM	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 Names: DARZALEX FASPRO(TM)
Experimental: Dose Expansion Cohort C Evaluation of RP2D of NKTR-255 as monotherapy and in combination with rituximab in patients with R/R iNHL	Drug: NKTR-255 Q21 NKTR-255 administered by IV infusion every 21 days to establish safety and tolerability Drug: Rituximab Rituximab administered intravenously at specified dose on specified days Other Names: RITUXAN(R)

Outcome Measures

Primary Outcome Measures

Incidence of Treatment-Emergent Adverse Events and Serious Adverse Events of NKTR-255 as a single agent [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 SC [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 [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
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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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:

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 :

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Western Regional Medical Center - CTCA	Goodyear	Arizona	United States	85338
2	City of Hope	Duarte	California	United States	91010
3	University of California, San Francisco	San Francisco	California	United States	94143
4	H. Lee Moffitt Cancer Center and Research Institute	Tampa	Florida	United States	33612
5	Winship Cancer Institute, Emory University	Atlanta	Georgia	United States	30322
6	Rush University Medical Center	Chicago	Illinois	United States	60612
7	University of Michigan	Ann Arbor	Michigan	United States	48109
8	University of Minnesota	Minneapolis	Minnesota	United States	55455
9	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065
10	New York Medical College	Valhalla	New York	United States	10595
11	Duke University Health System	Durham	North Carolina	United States	27705
12	MD Anderson Cancer Center	Houston	Texas	United States	77030
13	Texas Oncology - Austin Midtown	Round Rock	Texas	United States	78681
14	Texas Oncology	Tyler	Texas	United States	75702
15	Virginia Cancer Specialists	Fairfax	Virginia	United States	22031
16	Oncology and Hematology Associates of Southwestern Virginia Inc.	Roanoke	Virginia	United States	24014
17	University of Washington	Seattle	Washington	United States	98109