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

• ClinicalTrials.gov Identifier: NCT04136756
• Recruitment Status: Recruiting
• First Posted: October 23, 2019
• Last Update Posted: March 12, 2021
• Sponsor: Nektar Therapeutics
• Information provided by (Responsible Party): Nektar Therapeutics

Study Description

Brief Summary:

Patients will receive intravenous (IV) NKTR-255 in 21-day treatment cycles. During the Part 1 dose escalation portion of the trial, NKTR-255 will be given as monotherapy. After determination of the recommended Phase 2 dose (RP2D) of NKTR-255, NKTR-255 will be evaluated in 3 expansion Cohorts in Part 2 with daratumumab subcutaneous (DARZALEX FASPRO TM) and rituximab. Cohort A will enroll Non-Hodgkin Lymphoma (NHL) patients that have relapsed after CAR-T therapy. Cohort B will enroll patients with relapsed/refractory Multiple Myeloma (MM). Cohort C will enroll patients with relapsed/refractory indolent Non-Hodgkin Lymphoma (iNHL).

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: Daratumumab; Drug: Rituximab	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 MM and 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 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 (Clinical Trial)
• Estimated 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 as a Single Agent in Relapsed or Refractory Hematological Malignancies
• Actual Study Start Date: October 7, 2019
• Estimated Primary Completion Date: April 2022
• Estimated Study Completion Date: September 2022

Arms and Interventions

Arm	Intervention/treatment
Experimental: Dose Escalation of NKTR-255; Patients will receive IV infusion of NKTR-255 every 21 or 28 days to establish RP2D.	Drug: NKTR-255; NKTR-255 administered by IV infusion every 21 or 28 days to establish safety and tolerability
Experimental: Dose Expansion of NKTR-255 alone; The selected RP2D of NKTR-255 will be evaluated in expansion cohorts. Cohort A in patients with relapsed NHL after CAR-T therapy as a salvage regimen to further characterize safety and tolerability. Cohort B1 will evaluate NKTR-255 in patients with MM with progressive disease who have had at least 3 prior lines of therapy treatment. Cohort C1 will evaluate patients with iNHL that has progressed during or following 1 or more prior systemic rituximab-containing (or another treatment with an anti-CD20 antibody-containing) regimens for lymphoma.	Drug: NKTR-255; NKTR-255 administered by IV infusion every 21 or 28 days to establish safety and tolerability
Experimental: Dose Expansion of NKTR-255 with Daratumumab; The selected RP2D of NKTR-255 will be evaluated in expansion Cohort B2, which will combine NKTR-255 with daratumumab in patients with MM with progressive disease who have had at least 3 prior lines of therapy treatment.	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 Name: DARZALEX FASPRO(TM)
Experimental: Dose Expansion of NKTR-255 with Rituximab; The selected RP2D of NKTR-255 will be evaluated in Cohort C2, which will combine NKTR-255 with rituximab in patients with iNHL that has progressed during or following 1 or more prior systemic rituximab-containing (or another treatment with an anti-CD20 antibody-containing) regimens for lymphoma.	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 Name: RITUXAN(R)

Outcome Measures

Primary Outcome Measures :

1. Incidence of Treatment-Emergent Adverse Events and Serious Adverse Events of NKTR-255 [ Time Frame: 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.
2. Incidence of Treatment-Emergent Adverse Events and Serious Adverse Events of NKTR-255 with Daratumumab [ Time Frame: 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
3. Incidence of Treatment-Emergent Adverse Events and Serious Adverse Events of NKTR-255 with Rituximab [ Time Frame: 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

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 80 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.
• 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.

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:

Cohort A 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.

Cohort B 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.

Cohort C 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.
• Patients who have had < 28 days since the last anti-cancer treatment, chemotherapy, biological therapy, or < 14 days from approved anti-myeloma agents, or systemic or inhaled steroid therapy at doses greater than 10 mg of prednisone or equivalent before administration of the first dose of study drug(s).
• Prolonged Fridericia's corrected QT interval (QTcF) > 450 ms for men and > 470 ms for women at Screening.
• Contraindication to or unable to receive daratumumab (Cohort B only)

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply

Contacts and Locations

Contacts

Contact: Nektar Recruitment; 855-482-8676; StudyInquiry@nektar.com

Contact: Medical Affairs; 855-482-8676; medicalaffairs@nektar.com

Locations

United States, Arizona

CTCA Phoenix; Recruiting

Goodyear, Arizona, United States, 85338

United States, California

City of Hope; Recruiting

Duarte, California, United States, 91010

University of California at San Francisco; Recruiting

San Francisco, California, United States, 94143

United States, Florida

H Lee Moffitt Cancer Center and Research Institute; Recruiting

Tampa, Florida, United States, 33612

United States, Georgia

Winship Cancer Institute, Emory University; Recruiting

Atlanta, Georgia, United States, 30322

United States, Illinois

Rush University Medical Center; Active, not recruiting

Chicago, Illinois, United States, 60612

United States, Michigan

University of Michigan; Recruiting

Ann Arbor, Michigan, United States, 48109

United States, Minnesota

University of Minnesota; Recruiting

Minneapolis, Minnesota, United States, 55455

United States, New York

Memorial Sloan Kettering Cancer Center; Recruiting

New York, New York, United States, 10065

New York Medical College; Recruiting

Valhalla, New York, United States, 10595

United States, North Carolina

Duke University Health System; Recruiting

Durham, North Carolina, United States, 27705

United States, Texas

MD Anderson Cancer Center; Recruiting

Houston, Texas, United States, 77030

United States, Virginia

Virginia Cancer Specialists; Recruiting

Fairfax, Virginia, United States, 22031

United States, Washington

University of Washington; Recruiting

Seattle, Washington, United States, 98109

Sponsors and Collaborators

Nektar Therapeutics

Investigators

• Study Director: Study Director; Nektar Therapeutics

More Information

• Responsible Party: Nektar Therapeutics
• ClinicalTrials.gov Identifier: NCT04136756
• Other Study ID Numbers: 18-255-02
• First Posted: October 23, 2019
• Last Update Posted: March 12, 2021
• Last Verified: March 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Nektar Therapeutics:

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

Additional relevant MeSH terms:

Lymphoma; Multiple Myeloma; Neoplasms, Plasma Cell; Lymphoma, Non-Hodgkin; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemorrhagic Disorders; Rituximab; Daratumumab; Antineoplastic Agents, Immunological; Antineoplastic Agents; Immunologic Factors; Physiological Effects of Drugs; Antirheumatic Agents