The first patient has been dosed in Artiva Biotherapeutics phase 1 clinical trial (NCT06265220) evaluating AlloNK (AB-101), an investigational allogeneic natural killer (NK) cell therapy, alone or as part of a combination therapy with an antiCD20 monoclonal antibody in patients with systemic lupus erythematosus (SLE) and active lupus nephritis (LN).1
The multicenter, open-label clinical trial is recruiting patients aged 18 to 99 years with class III or class IV LN whose previous treatments with standard of care options did not succeed. AlloNK will be administered alone or alongside 1 of 2 antiCD20 monoclonal antibodies: rituximab or obinutuzumab. Participants will undergo lymphodepletion with cyclophosphamide and fludarabine, and then receive AlloNK, which will be administered in 3 doses, and the monoclonal antibody, which will be administered in 2 doses. According to the clinicaltrials.gov page, which was most recently updated on February 20, 2024, the study is currently recruiting at the University of California, San Diego. Artiva is collaborating with the Lupus Research Alliance’s clinical research affiliate Lupus Therapeutics on the development of AlloNK in lupus.
AlloNK, which is intended to heighten the B-cell depleting effect of the monoclonal antibodies via antibody-dependent cellular cytotoxicity (ADCC), is unengineered and derived from cord blood units selected for the high affinity variant of the CD16 receptor and the KIR-B haplotype.2 AlloNK is already being evaluated in 2 separate clinical trials for lymphoma indications: a multicenter phase 1/2 clinical trial (NCT04673617) both alone and in combination with rituximab for the treatment of relapsed/refractory (r/r) B-cell non-Hodgkin lymphoma (B-NHL) and the multicenter, open-label phase 2 LuminICE-203 clinical trial (NCT05883449) in combination with innate cell engager AFM13 in patients with r/r CD30-positive lymphomas.
“We are excited to bring AlloNK to patients with autoimmune disease,” Fred Aslan, MD, the chief executive officer of Artiva, said in a statement.1 “To our knowledge, this is the first time a patient has received an allogeneic NK cell therapy candidate in a United States clinical trial for treatment of an autoimmune disease. We are encouraged by the activity of AlloNK in our NHL trial, demonstrating AlloNK’s ability to drive B-cell depletion and helping validate the therapy’s potential mechanism of action. Furthermore, our ability to combine AlloNK with CD20, CD19, or CD38 directed monoclonal antibodies gives AlloNK the versatility to target distinct B-cell subpopulations across different autoimmune diseases.”
Key Takeaways
- The first patient has been dosed in Artiva Biotherapeutics phase 1 clinical trial (NCT06265220) evaluating AlloNK (AB-101), an investigational allogeneic natural killer (NK) cell therapy, alone or as part of a combination therapy with an antiCD20 monoclonal antibodyin patients with systemic lupus erythematosus (SLE) and active lupus nephritis (LN).
- AlloNK will be administered alone or alongside 1 of 2 antiCD20 monoclonal antibodies: rituximab or obinutuzumab.
- AlloNK is already being evaluated in 2 separate clinical trials for lymphoma indications: a multicenter phase 1/2 clinical trial (NCT04673617) both alone and in combination with rituximab for the treatment of relapsed/refractory (r/r) B-cell non-Hodgkin lymphoma (B-NHL) and the multicenter, open-label phase 2 LuminICE-203 clinical trial (NCT05883449) in combination with innate cell engager AFM13 in patients with r/r CD30-positive lymphomas.
The investigational new drug application for the phase 1 clinical trial was originally cleared by the FDA in August 2023.2 AlloNK in combination with rituximab or obinutuzumab for LN has also received fast track designation from the agency.1
“Lupus nephritis is among the most severe manifestations of systemic lupus erythematosus,” Kenneth Kalunian, MD, professor of medicine and director of the Lupus Center of Excellence at UC San Diego School of Medicine, added to the statement.1 “Many patients do not respond to standard therapies. Examining new treatments could provide more novel options for this patient demographic.”
Artiva is one of several companies pursuing an antiCD20-based cell therapy approach to treating autoimmune disease. In August 2023, ImmPACT Bio’s IMPT-514, an investigational bispecific CD19/CD20-directed CAR-T therapy, received clearance of an investigational new drug (IND) application from the FDA for a clinical trial in patients with active, refractory systemic lupus erythematosus (SLE).3 More recently, in April 2024, Mustang Bio announced its intention to pursue a phase 1 investigator-sponsored clinical trial for the evaluation of MB-106, an investigational autologous CD20-directed chimeric antigen receptor T-cell therapy originally developed for the treatment of hematological malignancies, in autoimmune disease.4
REFERENCES
1. Artiva Biotherapeutics announces first patient dosed in phase 1 trial of AlloNK® cell therapy candidate in lupus nephritis. News release. Artiva Biotherapeutics, Inc. April 17, 2024. Accessed April 25, 2024. https://www.artivabio.com/artiva-biotherapeutics-announces-first-patient-dosed-in-phase-1-trial-of-allonk-cell-therapy-candidate-in-lupus-nephritis/
2. Artiva Biotherapeutics announces FDA clearance of IND for AlloNK cell therapy candidate in combination with rituximab in lupus nephritis. News release. Artiva Biotherapeutics, Inc. August 16, 2023. Accessed April 25, 2024. https://www.artivabio.com/artiva-biotherapeutics-announces-fda-clearance-of-ind-for-allonk-cell-therapy-candidate-in-combination-with-rituximab-in-lupus-nephritis/
3. ImmPACT Bio announces FDA clearance of IND application for bispecific CD19/CD20 CAR T therapy IMPT-514 for the treatment of refractory systemic lupus erythematosus. News release. ImmPACT Bio USA, Inc. August 15, 2023. Accessed April 25, 2024. https://immpact-bio.com/news-and-events/immpact-bio-announces-fda-clearance-of-ind-application-for-bispecific-cd19-cd20-car-t-therapy-impt-514-for-the-treatment-of-refractory-systemic-lupus-erythematosus/
4. Mustang Bio announces vision for CAR t-cell therapy platform expansion into autoimmune diseases. News release. Mustang Bio, Inc. March 28, 2024. Accessed April 25, 2024. https://ir.mustangbio.com/news-events/press-releases/detail/177/mustang-bio-announces-vision-for-car-t-cell-therapy
