Session: 616. Acute Myeloid Leukemia: Novel Therapy, excluding Transplantation: Poster I
Hematology Disease Topics & Pathways:
Biological, AML, Diseases, Therapies, CAR-Ts, MDS, Myeloid Malignancies, Clinically relevant, NK cells
Methods: This is a multicenter, open-label, Phase 1 study of NKX101 (Figure). The study will be conducted in 2 parts: Part 1 (dose finding) to determine the recommended Phase 2 dose (RP2D) of NKX101 utilizing a modified “3+3” enrollment schema. The study will enroll subjects with either R/R primary or secondary AML or R/R higher-risk MDS. Building on existing clinical data referenced above with non-engineered haplomatched NK cells, NKX101 manufactured from NK cells obtained from haplo‑identical–related donors (H) will be used in Part 1. Part 2 (dose expansion) will further evaluate safety and tolerability, pharmacokinetics (PK), immunogenicity, pharmacodynamics (PDn), and anti‑tumor activity of NKX101 from unrelated, HLA-mismatched donors with separate expansion cohorts for patients with AML or MDS. Each dose is defined by the total number of viable CAR NK cells. The starting dose of NKX101 is 1 × 108 viable CAR NK cells where NKX101 will be administered on Days 0, 7, and 14 of a 28‑day cycle following standard fludarabine/cyclophosphamide lymphodepletion. Three dose levels are planned (Table). The primary endpoint is incidence of adverse events, dose-limiting toxicities, clinically significant laboratory abnormalities, and determination of the RP2D. Secondary endpoints include evaluation of standard cellular PK parameters, PDn, immunogenicity, and anti-tumor responses. AML patients will be assessed for efficacy using updated ELN criteria (Döhner 2017) including measurable residual disease assessment, and MDS using modified IWG criteria (Cheson 2006). Exploratory endpoints are correlation of various degrees of HLA and KIR ligand match/mismatch between donor and recipient with primary and secondary safety, PK, and efficacy measures. Enrollment across multiple US sites is expected to start in late 2020.
Disclosures: Bachier: CRISPR: Honoraria; Juno Therapeutics, a Bristol-Myers Squibb Company: Honoraria; AlloVir: Honoraria; Sanofi: Speakers Bureau. Borthakur: Novartis: Research Funding; FTC Therapeutics: Consultancy; Curio Science LLC: Consultancy; BioTherix: Consultancy; Nkarta Therapeutics: Consultancy; Treadwell Therapeutics: Consultancy; Incyte: Research Funding; AstraZeneca: Research Funding; Cyclacel: Research Funding; Argenx: Consultancy; Abbvie: Research Funding; Jannsen: Research Funding; PTC Therapeutics: Research Funding; GSK: Research Funding; Oncoceutics: Research Funding; Xbiotech USA: Research Funding; BioLine Rx: Research Funding; Polaris: Research Funding; BioLine Rx: Consultancy; PTC Therapeutics: Consultancy; BMS: Research Funding. Hosing: NKARTA Inc.: Consultancy. Blum: Amerisource Bergen: Honoraria; Celyad: Research Funding; Xencor: Research Funding; Leukemia and Lymphoma Society: Research Funding; Syndax: Membership on an entity's Board of Directors or advisory committees. Rotta: Merck: Speakers Bureau; Jazz Pharma: Speakers Bureau. Ojeras: Nkarta Therapeutics: Current Employment, Current equity holder in publicly-traded company. Barnett: Nkarta Therapeutics: Current Employment, Current equity holder in publicly-traded company. Rajangam: Nkarta Therapeutics: Current Employment, Current equity holder in publicly-traded company. Majhail: Mallinckrodt: Honoraria; Anthem, Inc.: Consultancy; Incyte: Honoraria; Nkarta Therapeutics: Honoraria. Nikiforow: Kite/Gilead: Honoraria; Nkarta Therapeutics: Honoraria; Novartis: Honoraria.
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