NKTR-255 in Relapsed/Refractory Multiple Myeloma & Non Hodgkin Lymphoma & Combined With Daratumumab for Multiple Myeloma

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

Study Description

Brief Summary:

Patients will receive intravenous 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, approximately 18 Multiple Myeloma (MM) or non-Hodgkin lymphoma (NHL) patients who may have received a chimeric antigen receptor T-cell (CAR-T) product and had progressive disease (PD) will receive NKTR-255 and approximately 18 MM patients who previously received daratumumab or other anti-CD38 therapies will receive NKTR-255 and daratumumab.

Phase 1 study to evaluate safety and tolerability of NKTR-255 along and in combination with daratumumab in subjects with relapsed/refractory NHL and multiple myeloma.

Condition or disease	Intervention/treatment	Phase
Multiple Myeloma; Non Hodgkin Lymphoma	Drug: NKTR-255; 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 daratumumab. 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.

The NKTR-255 starting dose in Dose Group 1 will be 1.5 µg/kg. Patients will receive intravenous (IV) NKTR-255 in 21-day cycles, starting on Cycle 1 Day 1.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 82 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 and in Combination With Daratumumab as a Salvage Regimen for Multiple Myeloma
• Actual Study Start Date: October 7, 2019
• Estimated Primary Completion Date: May 2021
• Estimated Study Completion Date: November 2021

Arms and Interventions

Arm	Intervention/treatment
Experimental: Dose Escalation of NKTR-255; The NKTR-255 starting dose will be 1.5 µg/kg. Patients will receive intravenous (IV) NKTR-255 every 21 days (q21d) to establish RP2D.	Drug: NKTR-255; NKTR-255 administered by intravenous infusion (IV) every 21 days to establish safety and tolerability
Experimental: Dose Expansion of NKTR-255 alone and with Daratumumab; The selected RP2D of NKTR-255 will be evaluated in 2 expansion Cohorts (A and B). Cohort A will expand NKTR-255 in patients with relapsed MM or NHL as a salvage regimen to further characterize safety and tolerability. Cohort B will combine NKTR-255 with daratumumab in patients with MM with progressive disease who have had at least 3 prior lines of therapy treatment may continue if there is clinical benefit as determined by the Investigator.	Drug: NKTR-255; NKTR-255 administered by intravenous infusion (IV) every 21 days to establish safety and tolerability; Drug: Daratumumab; Daratumumab administered by IV at a dose of 16 mg/kg weekly for 8 weeks, then every 2 weeks for 16 weeks, and then every 4 weeks thereafter; Other Name: Darzalex

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

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 75 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.
• No active central nervous system (CNS) involvement with NHL.
• 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 ≥ 800/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 may have 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.
• Patients with MM may have received a B cell maturation antigen (BCMA) 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 6 months washout

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.

• 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 6 months washout
• Patients who have had < 28 days since the last anti-cancer treatment, chemotherapy, biological therapy, or < 14 days from approved tyrosine kinase inhibitor therapy (sunitinib, sorafenib, vemurafenib, dabrafenib, cobimetinib), 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)

Contacts and Locations

Contacts

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

Contact: Rebecca Sutton; 855-482-8676

Locations

United States, Arizona

California Treatment Centers of America; Recruiting

Goodyear, Arizona, United States, 85338

United States, California

University of California at San Francisco; Not yet recruiting

San Francisco, California, United States, 94143

United States, Florida

H Lee Moffitt Cancer Center and Research Institute; Not yet recruiting

Tampa, Florida, United States, 33612

United States, Georgia

Winship Cancer Institute, Emory University; Not yet recruiting

Atlanta, Georgia, United States, 30322

United States, Michigan

University of Michigan; Not yet recruiting

Ann Arbor, Michigan, United States, 48109

United States, New York

Memorial Sloan Kettering Cancer Center; Not yet recruiting

New York, New York, United States, 10065

New York Medical College; Not yet recruiting

Valhalla, New York, United States, 10595

United States, North Carolina

Duke University Health System; Not yet recruiting

Durham, North Carolina, United States, 27705

United States, Texas

MD Anderson Cancer Center; Not yet recruiting

Houston, Texas, United States, 77030

United States, Virginia

Virginia Cancer Specialists; Not yet recruiting

Fairfax, Virginia, United States, 22031

United States, Washington

University of Washington; Not yet recruiting

Seattle, Washington, United States, 98109

Sponsors and Collaborators

Nektar Therapeutics

Investigators

• Study Director: Mario Marcondes, MD, PhD; Nektar Therapeutics

More Information

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

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; interleukin-15 (IL-15); MM; NHL

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; Daratumumab; Antibodies, Monoclonal; Antineoplastic Agents; Immunologic Factors; Physiological Effects of Drugs