Session: 704. Cellular Immunotherapies: Early Phase Clinical Trials and Toxicities: Poster I
Hematology Disease Topics & Pathways:
Research, Clinical trials, Clinical Research
Methods: This is a phase 2 randomized, double-blind, placebo-controlled, multicenter study of NKTR-255 vs placebo following CD19 CAR-T therapy. Eligible patients with R/R LBCL were treated with one of two FDA-approved CAR-T products (axicabtagene ciloleucel or lisocabtagene maraleucel). Patients received study drug intravenously starting +14 days following CAR-T infusion, with continued dosing every 21 days for up to 5 months. The primary endpoint was complete response rate (CRR) by blinded independent central review (BICR) at month 6 after CD19 CAR-T cells with NKTR-255 compared with placebo. Efficacy was assessed by PET-CT reported according to Lugano Response Criteria 2014. Key secondary and exploratory objectives included safety/tolerability, NKTR-255 PK and CAR-T PD. CAR-T cells were quantified by flow and ddPCR. Treatment related adverse events (TRAEs) were reported from the start of NKTR-255 treatment.
Results: A total of 15 patients with LBCL were randomized between Mar and Dec 2023. All patients received CD19 CAR-T cell therapy and ≥1 dose of study treatment; 12/15 (80%) received axi-cel and 3/15 (20%) received liso-cel preceding NKTR-255 or placebo. In total, 11 were randomized to the NKTR-255 group (5 at 1.5 µg/kg; 3 at 3.0 µg/kg; 3 at 3 µg/kg then 6 µg/kg cycle 2+) and 4 were randomized to placebo. LDH and histology was similar between the NKTR-255 and placebo groups, with the exception of tumor burden (NKTR-255 group median 1408 vs 940 mm2 for placebo). Treatment with NKTR-255 following CAR-T was well-tolerated. Among the 11 who received NKTR-255, infusion-related reaction (IRR) and fever was reported in 2/11 (18%) and 3/11 (27%) pts, respectively; these occurred ~6-8 hrs after infusion, all were grade 1/2 and resolved within 24 hrs with supportive care alone. No IRR or fever was reported with placebo. The most common grade ≥3 TRAEs reported with NKTR-255 in >1 patient was neutrophil count decrease 5/11 (46%), platelet count decrease 2/11 (18%), and lymphocyte count decrease 2/11 (18%); all resolved with no clinical sequelae. One patient had a grade 5 event of Guillain-Barré-syndrome on axi-cel with symptoms beginning prior to NKTR-255 and was deemed not related to study treatment by an independent DMC. Per intent-to-treat and BICR efficacy, the CRR at month 6 for the NKTR-255 group was 8/11 (73%) vs 2/4 (50%) with placebo. Per investigator, the conversions rate from SD/PR to CR at month 6 for the NKTR-255 group was 2/8 (25%) vs 0/2 (0%) with placebo. Per response-evaluable population by Investigator assessment, CRR at month 6 for the NKTR-255 group was 8/10 (80%) vs 2/4 (50%) with placebo. Notable re-expansion of CD8+ CAR-T cells occurred in 8/11 (73%) for NKTR-255 group vs 0/4 (0%) with placebo. NKTR-255 PK results were consistent with prior reported data. Additional longitudinal correlative analyses will be presented at the meeting.
Conclusions: Preliminary data from the randomized, double-blind, placebo-controlled study showed NKTR-255 adjuvant to CD19 CAR-T cell therapy in LBCL was well-tolerated, safe and efficacious to enhance the CR rate of CD19 CAR-T cell therapy alone at month 6. Additional confirmatory studies with NKTR-255 as adjuvant treatment to CAR-T therapy and other cellular therapies are warranted.
Disclosures: Ahmed: Janssen: Research Funding; Kite, a Gilead Company: Consultancy, Research Funding; Nektar: Research Funding; Myeloid Therapeutics: Consultancy; Merck: Research Funding; Xencor: Research Funding; Bristol Myers Squibb: Research Funding; ADC Therapeutics: Consultancy. DiPersio: NeoImmune Tech: Research Funding; Macrogenics: Research Funding; Bioline Rx: Research Funding; hC Bioscience, Inc.: Membership on an entity's Board of Directors or advisory committees; Vertex: Consultancy; SPARC: Consultancy; RiverVest Venture Partners: Consultancy, Membership on an entity's Board of Directors or advisory committees; WUGEN: Current equity holder in private company, Research Funding; Magenta Therapeutics: Current equity holder in publicly-traded company, Membership on an entity's Board of Directors or advisory committees. Essell: Canopy Care: Current equity holder in private company; Genmab: Speakers Bureau; AbbVie: Speakers Bureau; Kite: Speakers Bureau; BMS: Consultancy, Speakers Bureau. Diefenbach: NYU Grossman School of Medicine/Perlmutter Cancer Center at NYU Langone Health: Current Employment; Gilead Sciences: Current equity holder in publicly-traded company; OverT Therapeutics: Current equity holder in private company; Abbvie: Membership on an entity's Board of Directors or advisory committees, Research Funding; Astra Zeneca: Membership on an entity's Board of Directors or advisory committees; BMS: Consultancy, Research Funding; Celgene: Consultancy; FATE Therapeutics: Research Funding; Genentech/Roche: Consultancy, Research Funding; Genmab: Consultancy; I MAB: Consultancy; Incyte: Consultancy, Research Funding; MEI Pharma: Research Funding; Merck: Consultancy, Research Funding; Millenium: Research Funding; MorphoSys: Consultancy; Seattle Genetics: Consultancy, Research Funding. Perales: Omeros: Consultancy, Current equity holder in publicly-traded company; Merck: Consultancy, Research Funding; Incyte: Consultancy, Honoraria, Research Funding; Kite/Gilead: Consultancy, Honoraria, Research Funding; Vor Biopharma: Consultancy; AbbVie: Honoraria; Sanofi: Consultancy; Allogene: Consultancy, Research Funding; Syncopation: Consultancy; Allovir: Consultancy; Nektar Therapeutics: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Research Funding; Sellas: Other: DSMB member; Cidara Therapeutics: Other: DSMB member; Caribou Biosciences: Consultancy; Adicet: Consultancy; OrcaBio: Consultancy, Current holder of stock options in a privately-held company; Miltenyi Biotec: Consultancy, Honoraria, Research Funding; VectivBio AG: Consultancy, Research Funding; Celgene: Consultancy, Honoraria; Bristol-Myers Squibb: Consultancy, Honoraria; Astellas: Honoraria; Karyopharm: Honoraria; MorphoSys: Honoraria; Takeda: Honoraria; Medigene: Other: DSMB member; Servier: Other: DSMB member. Dahiya: Kite/Gilead, BMS, Incyte, Adaptive biotechonologies: Consultancy. Chaudhry: Nektar Therapeutics: Current Employment, Current equity holder in publicly-traded company. Xu: Nektar Therapeutics: Current Employment, Current equity holder in publicly-traded company. Liu: Nektar Therapeutics: Current Employment, Current equity holder in publicly-traded company. Fanton: Nektar Therapeutics: Current Employment, Current equity holder in publicly-traded company. Lee: Nektar Therapeutics: Current Employment, Current equity holder in publicly-traded company. Marcondes: Nektar Therapeutics: Current Employment, Current equity holder in publicly-traded company. Tagliaferri: Nektar Therapeutics: Current Employment, Current equity holder in publicly-traded company. Zalevsky: Nektar Therapeutics: Current Employment, Current equity holder in publicly-traded company. Miklos: Fosun Kite Biotechnology: Honoraria; Janssen: Consultancy, Patents & Royalties; Adaptive Biotechnologies: Research Funding; Allogene: Research Funding; Kite, a Gilead Company: Consultancy, Other: Travel Support, Research Funding; Juno Therapeutics: Consultancy; 2SeventyBio: Research Funding; Novartis: Consultancy; Miltenyi: Consultancy, Research Funding; Galapagos: Consultancy; Adicet: Research Funding; Bristol Myers Squibb: Consultancy. Turtle: ArsenalBio: Current holder of stock options in a privately-held company; Cargo Therapeutics: Current holder of stock options in a privately-held company, Membership on an entity's Board of Directors or advisory committees; Kyverna: Membership on an entity's Board of Directors or advisory committees; Advesya: Membership on an entity's Board of Directors or advisory committees; Celgene, a BMS company: Membership on an entity's Board of Directors or advisory committees; Boxer Capital: Consultancy; Prescient Therapeutics: Consultancy; Myeloid Therapeutics: Membership on an entity's Board of Directors or advisory committees; Caribou Biosciences: Current holder of stock options in a privately-held company, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy; Juno Therapuetics, a BMS company: Research Funding; Abbvie: Consultancy; Myeloid Therapeutics: Current holder of stock options in a privately-held company; Nektar Therapeutics: Research Funding; IGM Biosciences: Consultancy; eGlint: Current holder of stock options in a privately-held company, Membership on an entity's Board of Directors or advisory committees; ArsenalBio: Membership on an entity's Board of Directors or advisory committees; T-CURX: Membership on an entity's Board of Directors or advisory committees; Eureka Therapeutics: Current holder of stock options in a privately-held company; Differentia Bio: Membership on an entity's Board of Directors or advisory committees; Century Therapeutics: Consultancy. McGuirk: CRISPR therapeutics: Consultancy; Sana technologies: Consultancy; Caribou bio: Consultancy; Legend biotech: Consultancy; Autolus: Consultancy; NEKTAR therapeutics: Consultancy; Envision: Consultancy; Allo Vir: Consultancy; Novartis: Consultancy; Kite: Consultancy; BMS: Consultancy.
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