Open Label, Phase 1 study of CD19 t-haNK as a single agent and combination with rituximab in subjects with selected CD19+ and CD20+ R/R B-cell non-Hodgkin Lymphoma( NHL).
This is a Phase 1, first-in-human (FIH), open-label study to evaluate the safety of CD19 t-haNK as a single agent and the safety and preliminary efficacy of CD19 t-haNK in combination with rituximab in participants with selected CD19+ and CD20+ R/R B-cell non-Hodgkin lymphoma (NHL). Up to 20 participants will receive at least 1 dose of study drug. The initial 3 participants will receive study drug in a staggered fashion, with a 7-day interval between each participant to evaluate the safety profile of the investigational product. Participants will initially receive a single 3-week cycle of the CD19 t-haNK as a single-agent regimen. Following a 1-week safety pause, participants will then receive a 3-week cycle of CD19 t-haNK in combination with rituximab. Participants will then undergo the first tumor assessment. Participants with no evidence of progressive disease (PD) will be eligible to receive up to 2 additional 3-week cycles of CD19 t-haNK in combination with rituximab
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
20
CD19t-haNK erived from the parental NK-92 (aNK) cell line, CD19 t-haNK is a human, allogeneic, NK cell line that has been engineered to express a CAR targeting CD19. Similar to the haNK cell line, CD19 t haNK has also been engineered to produce endoplasmic reticulum-retained IL 2 and the high-affinity (158V) variant of the Fcγ receptor (FcγRIIIa/CD16a), and thereby has enhanced CD16-targeted ADCC capabilities. CD19 t-haNK is similar to PD L1 t-haNK, differing only in the CAR that is expressed (CD19 vs PD-L1). Rituximab is a genetically engineered chimeric murine/human monoclonal IgG1 kappa antibody directed against the CD20 antigen. Rituximab has an approximate molecular weight of 145 kD and has a binding affinity for the CD20 antigen of approximately 8.0 nM.
FARMOVS
Bloemfontein, Free State, South Africa
Dr. Jackie Thomson Inc.
Johannesburg, Gauteng, South Africa
Albert Cellular Therapy
Pretoria, Gauteng, South Africa
Overall safety evaluation in combining CD19 t haNK as a single agent with rituximab
Safety will be assessed for all participants and will include vital signs, physical examinations, clinical labs (hematology, chemistry panel, pregnancy tests), cytokine levels, electrocardiograms, neurological assessments, and the incidence and severity of adverse events (AEs) graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0. All participants will receive follow-up phone calls 6 hours (± 1 hour) and 24 hours (± 2 hours) post infusion for AE collection during Cycle 1
Time frame: 30 days
Incidence of treatment-emergent AEs (TEAEs) and serious AEs (SAEs) graded using the National Cancer Institute (NCI) CTCAE Version 5.0.Clinically important changes in safety laboratory tests and vital signs.
The incidence of TEAEs and SAEs will be presented by System Organ Class and Medical Dictionary for Regulatory Activities (MedDRA) preferred term. All AEs will be graded using CTCAE Version 5.0 except for CRS and ICANS, which will be graded using ICE score. The incidence of clinically important changes in safety laboratory tests and vital signs will also be presented.
Time frame: 12 months
Best tumor response in accordance with Lymphoma Response to Immunomodulatory Therapy Criteria (LYRIC).
Tumors will be assessed at screening, and tumor response will be assessed by the Investigator after Cycle 2 (± 1 week) has been completed and at the end of treatment (EOT) visit by positron emission tomography (PET)/computed tomography (CT) in accordance with LYRIC.
Time frame: 12 Months
Overall Survival (OS)
OS will be evaluated using Kaplan-Meier methods. OS will be defined as the time from the date of first treatment to the date of death (any cause). Participants who are alive at the end of follow-up will be censored at the last known date alive.
Time frame: 12 Months
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