Kyverna’s Lupus Nephritis CAR-T Generally Well-Tolerated in First Patient Treated in the US

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Kyverna stated that the patient, who received KYV-101 in July at the University of Colorado Anschutz Medical Campus, did not experience any ICANS.

Kyverna Therapeutics’ KYV-101, an investigational chimeric antigen receptor T-cell (CAR-T) therapy intended to treat relapsed/refractory lupus nephritis (LN), was generally well-tolerated at 28 days-posttreatment in the first patient to receive the therapy in the US in a phase 1 clinical trial (NCT05938725).1

Kyverna stated that the patient, who received KYV-101 in July at the University of Colorado Anschutz Medical Campus, did not experience any immune effector cell-associated neurotoxicity syndrome (ICANS). The US trial is seeking to recruit approximately 9 to 12 patients with LN in total across several clinical sites. In addition to the US trial, KYV-101 also recently received clearance of a clinical trial application from the Paul-Ehrlich-Institut in Germany in July 2023.2 Kyverna noted that patients in Europe are receiving KYV-101 for the treatment of multiple indications.

“We expect to present data from more patients in the coming months and at our symposium at the American College of Rheumatology Convergence Meeting this November in San Diego,” Peter Maag, PhD, the chief executive officer of Kyverna Therapeutics, said in a statment.1 “Our ability to consistently deliver on our promise of a seamless patient experience is a testament to our commitment to become best-in-class in the treatment of B-cell-driven autoimmune diseases.”

KYV-101 is an autologous version of a CD19-directed fully human CAR-T construct. The construct has previously been evaluated in a phase 1 clinical trial (NCT02659943) sponsored by the National Cancer Institute for patients with B-cell lymphomas and patients with chronic lymphocytic leukemia where it demonstrated antilymphoma activity that was associated with a reduction in cytokine-driven adverse events, including ICANS, and reduced immunogenicity, in comparison to a CAR-T product expressing FMC63-28Z and containing murine binding domains.1,3

“There is a growing need for therapies that can drive greater and more rapid reduction of disease activity in patients with LN,” Amber Podoll, MD, FASN, an associate professor at University of Colorado Anschutz Medical Campus and a principal investigator on the US study in LN, added to the statement.1 “Cell-based therapies offer a potential new approach to very complex, and often challenging to treat, severe medical conditions.”

Earlier this month, Kyverna also announced a new collaboration with health technology company Verily.4 As part of the collaboration, Verily is lending support in the form of its immune mapping platform, Immune Profiler, to Kyverna’s efforts in the clinical evaluation of KYV-101. Immune Profiler will be used to help identify biomarkers for treatment response that may help improve the design of and process of carrying out the clinical trials.

“We are excited to explore our emerging patient data set, which will enable us to generate a first look into the biology underlying immune reset after administration of CAR T-cell therapy,” James Chung, MD, PhD, the chief medical officer of Kyverna, said in a statement.4

KYV-101 is among several autologous cell therapies currently under evaluation for the treatment of systemic lupus erythematosus and/or LN. Others include ImmPACT Bio’s IMPT-514, an investigational bispecific CD19/CD20-directed CAR-T; Artiva Biotherapeutics’ AlloNK (AB-101), an investigational allogeneic natural killer cell therapy; and Cabaletta Bio’s CABA-201, an investigational CD19-directed CAR-T.5-7

REFERENCES
1. Kyverna Therapeutics announces achievement of 28-day post-infusion milestone for first U.S. patient dosed in phase 1 clinical trial of CD19 CAR t-cell therapy for lupus nephritis. News release. Kyverna Therapeutics. September 13, 2023. Accessed September 14, 2023. https://kyvernatx.com/press-releases/kyverna-therapeutics-announces-achievement-of-28-day-post-infusion-milestone-for-first-u-s-patient-dosed-in-phase-1-clinical-trial-of-cd19-car-t-cell-therapy-for-lupus-nephritis/
2. Kyverna Therapeutics announces regulatory approval of phase 1/2 clinical trial for KYV-101 in Germany. Kyverna Therapeutics. News release. July 6, 2023. https://prnmedia.prnewswire.com/news-releases/kyverna-therapeutics-announces-regulatory-approval-of-phase-12-clinical-trial-for-kyv-101-in-germany-301870630.html
3. Brudno JN, Lam N, Vanasse D, et al. Safety and feasibility of anti-CD19 CAR T cells with fully human binding domains in patients with B-cell lymphoma. Nat Med. 2020;26(2):270-280. Doi: 10.1038/s41591-019-0737-3.
4. Verily and Kyverna Therapeutics announce collaboration to advance cell therapy for autoimmune diseases. News release. Kyverna Therapeutics. September 13, 2023. Accessed September 14, 2023. https://kyvernatx.com/press-releases/verily-and-kyverna-therapeutics-announce-collaboration-to-advance-cell-therapy-for-autoimmune-diseases/
5. 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 August 18, 2023. 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/
6. 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 August 18, 2023. https://www.artivabio.com/artiva-biotherapeutics-announces-fda-clearance-of-ind-for-allonk-cell-therapy-candidate-in-combination-with-rituximab-in-lupus-nephritis/
7. Cabaletta Bio receives FDA clearance of IND application for CABA-201 for treatment of systemic lupus erythematosus. News release. Cabaletta Bio, Inc. March 31, 2023. Accessed August 18, 2023. https://www.cabalettabio.com/news-media/press-releases/detail/81/cabaletta-bio-receives-fda-clearance-of-ind-application-for
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