nkx019, intravenous allogeneic chimeric antigen receptor natural killer cells (car nk), in adults with b-cell cancers

Conditions: Lymphoma, Non-Hodgkin; B-cell Acute Lymphoblastic Leukemia; Large B-cell Lymphoma; Mantle Cell Lymphoma; Indolent Lymphoma; Waldenstrom Macroglobulinemia; Chronic Lymphocytic Leukemia; Small Lymphocytic Lymphoma; Aggressive Lymphoma; Large-cell Lymphoma

Summary: this is a single arm, open-label, multi-center, phase 1 study to determine the safety and tolerability of an experimental therapy called nkx019 (allogeneic car nk cells targeting cd19) in patients with relapsed/refractory non-hodgkin lymphoma (nhl), chronic lymphocytic leukemia (cll) or b cell acute lymphoblastic leukemia (b-all)

this is a dose-finding study of nkx019 and will be conducted in 2 parts: part 1: dose finding utilizing a "3+3" enrollment schema and safety lead-in to confirm dose for nkx019 in combination with rituximab expansion cohorts (as applicable) part 2: dose expansion to further evaluate safety and tolerability, cellular kinetics, pharmacodynamics and anti-tumor response in expansion cohorts of patients with large b cell lymphoma (lbcl), mantle cell lymphoma (mcl), indolent lymphoma (il), waldenström macroglobulinemia (wm), cll/ small lymphocytic lymphoma (sll), and b-all.

Eligibility criteria:
inclusion criteria: general: eastern cooperative oncology group (ecog) performance status ≤1 • disease related: * have a histologically or cytologically confirmed diagnosis of r/r b cell nhl or cll or b-all as defined by who 2016 classification * subjects who received prior cd19/cd20-directed therapy must have disease that remains cd19+ and/or cd20+ respectively * have measurable disease * have received ≥2 lines of therapy except subjects with mcl, car t naïve cohorts and wm, who must have received at least 1 prior line of therapy * have received a combination of an anti cd20 monoclonal antibody and cytotoxic chemotherapy for subjects with nhl * received: * btki for subjects with mcl, cll/sll, wm, and other indications where a btki is approved * venetoclax for subjects with cll/sll * tyrosine kinase inhibitor for subjects with philadelphia chromosome (ph+) b-all * not responded or relapsed within 12 months of completion of their prior line of therapy, with the exception of a newly diagnosed richter's transformation of cll/sll or other transformation of an indolent lymphoma, including from wm * subjects must not have evidence of rapidly progressive disease that would preclude subject from completing at least 1 cycle of treatment. * adequate organ function * white blood cell count of ≤20 × 109/l * platelet count ≥30,000/ul exclusion criteria: • disease related: * burkitt lymphoma, primary central nervous system (cns) lymphoma, richter's transformation to hodgkin lymphoma * subjects with wm who underwent plasmapheresis \<35 days prior to the first dose of nkx019 * subjects with nhl with any evidence of active cns malignancy * subjects with b-all who have extramedullary disease (emd) * subjects with any prior cellular therapy except subjects enrolling in selected cohorts who must have received prior car t therapy, recent hct, or complications from hct * recent use of any cancer-directed therapy within protocol specified window prior to the first dose of nkx019 * residual toxicities ≥grade 2 due to prior therapy * other comorbid conditions and concomitant medications prohibited as per study protocol * pregnant or lactating female

Keywords: cd19 car allogeneic natural killer acr nkx019 il15 interleukin 15 nk cell cell therapy immunotherapy adoptive cell therapy r/r nhl r/r b-all r/r mcl r/r il r/r wm r/r cll r/r sll aggressive lymphoma indolent lymphoma lcl