Clinical trial NCT05020678: NKX019, Intravenous Allogeneic Chimeric Antigen Receptor Natural Killer Cells (CAR NK), in Adults With B-cell Cancers
Official title: A Phase 1 Study of NKX019, a CD19 Chimeric Antigen Receptor Natural Killer (CAR NK) Cell Therapy, in Subjects With B-cell Malignancies
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
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
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
Lead sponsor: Nkarta, Inc.
Sponsor class: INDUSTRY
First posted: 2021-08-25
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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)

Detailed description: 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

Primary outcomes:
measure: Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
timeFrame: 30 days after last dose of NKX019
measure: Proportion of subjects experiencing dose-limiting toxicities of NKX019
timeFrame: 28 days from first dose of NKX019
measure: Objective response rate to NKX019 in Part 2
timeFrame: Primary assessment: 28 days after the first dose of NKX019 followed up to 2 years after the last dose of NKX019]
Secondary outcomes:
measure: Assessment of NKX019 half-life
timeFrame: Time Frame: 28 days from first dose of NKX019
measure: NKX019 duration of persistence
timeFrame: Followed up to 2 years after last dose of NKX019
measure: Evaluation of host immune response against NKX019
timeFrame: Followed up to 2 years after last dose of NKX019
measure: Objective response rate to NKX019 in Part 1
timeFrame: Primary assessment: 28 days after first dose of NKX019 followed up to 2 years after last dose of NKX019
Other outcomes:
Locations:
city: Denver
country: United States
facility: Colorado Blood Cancer Institute
state: Colorado
city: Cleveland
country: United States
facility: The Cleveland Clinic Foundation
state: Ohio
city: Camperdown
country: Australia
facility: Institute of Haematology, Royal Prince Alfred Hospital
state: New South Wales
city: Sydney
country: Australia
facility: St. Vincent's Hospital
state: New South Wales
city: Brisbane
country: Australia
facility: Royal Brisbane and Woman's Hospital
state: Queensland
city: Melbourne
country: Australia
facility: Peter MacCallum Cancer Center
state: Victoria
Study officials:
affiliation: Nkarta, Inc.
name: David Shook, MD
role: STUDY_DIRECTOR
References: