nktr-255 in relapsed/refractory multiple myeloma & non-hodgkin lymphoma

Conditions: Multiple Myeloma; Non-Hodgkin Lymphoma; Indolent Non-Hodgkin Lymphoma

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.

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.

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. * 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: 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: 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

Keywords: relapsed refractory nktr-255 car-t daratumumab subcutaneous (sc) interleukin-15 (il-15) mm nhl indolent rituximab truxima®