Description:
Patients will receive intravenous (IV) NKTR-255 in 21 or 28 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 or biosimilar. 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.
Title
- Brief Title: 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
Clinical Trial IDs
- ORG STUDY ID:
18-255-02
- NCT ID:
NCT04136756
Conditions
- Multiple Myeloma
- Non-Hodgkin Lymphoma
- Indolent Non-Hodgkin Lymphoma
Interventions
Drug | Synonyms | Arms |
---|
NKTR-255 | | Dose Escalation of NKTR-255 |
Daratumumab | DARZALEX FASPRO(TM) | Dose Expansion of NKTR-255 with Daratumumab |
Rituximab | RITUXAN(R) | Dose Expansion of NKTR-255 with Rituximab |
Purpose
Patients will receive intravenous (IV) NKTR-255 in 21 or 28 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 or biosimilar. 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.
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.
Trial Arms
Name | Type | Description | Interventions |
---|
Dose Escalation of NKTR-255 | Experimental | Patients will receive IV infusion of NKTR-255 every 21 or 28 days to establish RP2D. | |
Dose Expansion of NKTR-255 alone | Experimental | 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. | |
Dose Expansion of NKTR-255 with Daratumumab | Experimental | 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. | |
Dose Expansion of NKTR-255 with Rituximab | Experimental | 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. | |
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.
- 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
Maximum Eligible Age: | 80 Years |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | 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 Issue: | |
Description: | 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. |
Details
Phase: | Phase 1 |
Primary Purpose: | Interventional |
Overall Status: | Recruiting |
Lead Sponsor: | Nektar Therapeutics |
Trial Keywords
- relapsed
- refractory
- NKTR-255
- CAR-T
- daratumumab subcutaneous (sc)
- interleukin-15 (IL-15)
- MM
- NHL
- indolent
- rituximab
- Truxima®
Last Updated
September 1, 2021