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
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 or ritixumab. NKTR-255 is a cytokine that is designed to regulate T and natural killer cell activation, proliferation and promote their anti-tumor effects.
Phase 2 dose (RP2D) of NKTR-255 as a single agent. Part 2 (Dose Expansion): To evaluate the safety and tolerability of NKTR-255 in patients with relapsed or refractory multiple myeloma (MM) or non-Hodgkin lymphoma (NHL); and To evaluate the safety and tolerability of NKTR-255
> Patients with multiple myeloma (MM) must have measurable relapsed or refractory MM as defined by the IMWG Consensus Criteria following treatment with at least 3 lines of therapy with no other available treatment that would confer benefit.
Measurable disease within at least one of the following: Serum M protein level ≥ 0.5 g/dL; or Urine M protein level ≥ 200 mg/24 hours; or Serum free light chain (FLC) assay: involved FLC level ≥ 10 mg/dL (100 mg/L) and an abnormal serum FLC ratio ( 1.65); or Extramedullary plasmacytoma (measured within 28 days of Screening) can be used to adjudicate response assessments by clinical investigators concurrently with either of above 3 markers.
Histologically confirmed CD19/CD20 positive NHL (including large B--cell lymphoma, high grade B--cell lymphoma, primary mediastinal large B-cell lymphoma (PMBCL), or DLBCL, arising from follicular lymphoma) confirmed by archived tumor biopsy tissue from last relapse fresh biopsy at the time of inclusion
Indolent Non--Hodgkin Lymphoma (iNHL)
Histologically confirmed CD19/CD20 positive diagnosis of iNHL (follicular lymphoma Grade 1, 2, 3a; marginal zone lymphoma; small lymphocytic lymphoma or lymphoplasmacytic lymphoma) confirmed by archived tumor biopsy tissue from last relapse or fresh biopsy at the time of inclusion.
Must have received treatment with at least 1 or more prior rituximab--containing regimens.
Anti--CD20 monoclonal antibody (mAb)-)-refractory disease OR anti-CD20 mAb-sensitive disease, as defined per protocol.
Patients with cutaneous only disease may be enrolled if they have a clearly measurable skin lesion.
Inclusion Criteria for Dose Expansion:
Patients are eligible who also meet all the following criteria in these cohorts of Part 2: Cohort A NHL only
Patients with NHL must have received a commercially approved CD19 CAR--T product and had PD. The first dose of NKTR--255 should be administered within 30 days of the PD.
Cohort B MM only:
Relapsed or refractory disease defined as PD while on therapy or progression within 60 days of therapy.
Progressive disease as defined by IMWG criteria (Appendix 2)
Previous exposure to proteasome inhibitor, IMiD, and anti--CD38 therapy
Patients who previously received daratumumab or other anti--CD38 therapies must have at least 3 months washout
Responded at least once to prior daratumumab treatment
Cohort C iNHL only:
Relapsed or refractory 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.
> 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.
History of allergy of hypersensitivity to study drug components
History of organ transplant that requires ongoing use of immune supressive agents
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 with less than 3 months washout
Use of warfarin within 14 days of initiating study drug(s)
Unresolved toxicity from previous anticancer therapy, unless resolved to Grade 1 or less, or Resolved to Grade 2 with exceptions outlined in study
Prior surgery or radiotherapy within 14 days of initiating study drug(s). Patients must have recovered from all radiation related toxicities, not required corticosteroids and have not had radiation pneumonitis.
Patients participating in observational studies should be discussed with the Medical Monitor to confirm eligibility.
Patients who have had over 28 days since the last anticancer treatment, chemotherapy, biological therapy, or over 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)
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