Session: 704. Cellular Immunotherapies: Early Phase and Investigational Therapies: Poster II
Hematology Disease Topics & Pathways:
Biological therapies, Research, clinical trials, Clinical Research, Immunotherapy, Therapies
Methods: This is a phase 2/3, randomized, double blind, placebo-controlled, multicenter study of NKTR-255 vs placebo following CD-19 directed CAR-T therapy. Eligible patients who have r/r large B-cell lymphoma and are planned for treatment with an FDA-approved CAR-T product (axi-cel or liso-cel) will be enrolled. All patients will receive initial study drug administration of NKTR-255 intravenously, starting approximately 14 days following CAR-T therapy, with continued dosing every 21 days. The study will be comprised of two stages: 1) Phase 2: patients will be randomized to placebo or one of multiple dose cohorts of NKTR-255 (Stage 1) and 2) Phase 3: patients will be randomized to placebo or the selected NKTR-255 dose regimen (Stage 2). The primary objective for Stage 1 is to identify the dose of NKTR-255 for the Phase 3 part of the study based on the safety and tolerability of NKTR-255 as well as the complete response rate (CRR) at month 6. The primary efficacy endpoints of Stage 2 are CRR at month 6 and event-free survival. Efficacy analyses will be performed separately for Stage 1 and Stage 2. Efficacy, as measured by PET-CT, will be evaluated according to the Lugano Criteria (Cheson 2014). The key eligibility criteria following CD19 targeted CAR-T cell infusion include no grade ≥ 1 cytokine release syndrome (CRS) on the day of NKTR-255 administration, no grade ≥ 3 CRS within 72 hours proceeding NKTR-255 administration, no grade ≥ 3 immune effector cell-associated neurotoxicity (ICANS) of > 72 hours duration, no grade ≥ 2 ICANS on the day of NKTR-255 infusion and no tocilizumab and/or dexamethasone within 48 hours proceeding NKTR-255 administration.
Conclusions: Based on preclinical and clinical evidence, NKTR-255 has the potential to improve efficacy of currently approved cellular therapies. This trial evaluates safety and efficacy of NKTR-255 following commercial CD19 CAR-T therapy to enhance antitumor effect and durability of responses.
Disclosures: Perales: Omeros: Consultancy; Nektar Therapeutics: Consultancy, Honoraria; Novartis: Honoraria; Celgene: Honoraria; Merck: Consultancy; Orca Bio: Consultancy; Miltenyi Biotec: Consultancy, Honoraria; Kite, a Gilead Company: Honoraria, Research Funding; Sellas Life Sciences: Consultancy; AbbVie: Honoraria; VectivBio AG: Honoraria; Astellas: Honoraria; MorphoSys: Consultancy, Honoraria; Takeda: Honoraria; Karyopharm: Honoraria; Vor Biopharma: Honoraria; Cidara Therapeutics: Consultancy; Medigene: Consultancy; Servier: Consultancy; Bellicum: Honoraria; DSMB: Other; Incyte: Honoraria, Research Funding; Bristol Myers Squibb: Honoraria. Ahmed: Myeloid Therapeutics: Consultancy; Tessa Therapeutics: Consultancy, Research Funding; Xencor: Research Funding; Chimagen: Consultancy, Research Funding; Servier: Membership on an entity's Board of Directors or advisory committees; Seagen: Research Funding; Merck: Research Funding. Riedell: Karyopharm: Membership on an entity's Board of Directors or advisory committees; Calibr: Research Funding; Nektar Therapeutics: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees; Intellia Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees; BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Xencor: Research Funding; Tessa Therapeutics: Research Funding; MorphoSys: Research Funding; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; BeiGene: Consultancy; Takeda: Membership on an entity's Board of Directors or advisory committees; Nurix Therapeutics: Membership on an entity's Board of Directors or advisory committees; Sana Biotechnology: Consultancy; Janssen: Membership on an entity's Board of Directors or advisory committees; Fate Therapeutics: Research Funding; Kite/Gilead: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. McGuirk: BMS: Consultancy, Honoraria, Speakers Bureau; Novartis: Consultancy, Honoraria; Nextar: Consultancy, Honoraria; Orca Bio: Research Funding; Magenta Therapeutics: Consultancy, Honoraria, Research Funding; Kite, a Gilead Company: Consultancy, Honoraria, Research Funding, Speakers Bureau; Allovir: Consultancy, Honoraria, Research Funding, Speakers Bureau; Juno Therapeutics: Consultancy, Honoraria, Research Funding; Sana: Honoraria; CRISPR Therapeutics: Consultancy; In8bio, Inc.: Other: IIT Clinical Trial. Oluwole: ADC Therapeutics: Consultancy; Janssen: Consultancy; Curio Science: Consultancy; Novartis: Consultancy; Kite, a Gilead Company: Research Funding; TG Therapeutics: Consultancy; Pfizer: Consultancy; Nektar: Consultancy; Syncopation: Consultancy; Epizyme: Consultancy. Chaudhry: Nektar Therapeutics: Current Employment. Lee: Nektar Therapeutics: Current Employment. Dai: Nektar Therapeutics: Current Employment. Dixit: Nektar Therapeutics: Current Employment. Fanton: Nektar Therapeutics: Current Employment. Marcondes: Nektar Therapeutics: Current Employment, Current equity holder in publicly-traded company, Current holder of stock options in a privately-held company. Zalevsky: Nektar Therapeutics: Current Employment. Tagliaferri: Nektar Therapeutics: Current Employment. Turtle: Juno Therapeutics, a BMS Company: Patents & Royalties, Research Funding; GlaxoSmithKline: Membership on an entity's Board of Directors or advisory committees; Decheng Capital: Consultancy, Membership on an entity's Board of Directors or advisory committees; Expert Connect: Consultancy; Allogene: Membership on an entity's Board of Directors or advisory committees; Myeloid Therapeutics: Current holder of stock options in a privately-held company, Membership on an entity's Board of Directors or advisory committees; Caribou Bioscience: Current holder of stock options in a privately-held company, Membership on an entity's Board of Directors or advisory committees; Eureka Therapeutics: Current holder of stock options in a privately-held company, Membership on an entity's Board of Directors or advisory committees; T-CURX: Membership on an entity's Board of Directors or advisory committees; Kite Pharma, a Gilead Company: Membership on an entity's Board of Directors or advisory committees; Century Therapeutics: Membership on an entity's Board of Directors or advisory committees; Arsenal Bio: Current holder of stock options in a privately-held company, Membership on an entity's Board of Directors or advisory committees; Precision Bioscience: Current holder of stock options in a privately-held company, Membership on an entity's Board of Directors or advisory committees; Nektar Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Prescient Therapeutics: Membership on an entity's Board of Directors or advisory committees.
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