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4860 Phase I/II Study to Evaluate the Safety, Feasibility, and Efficacy of FP-1201 (Intravenous Interferon-Beta-1a) to Prevent Toxicities after CD19-Directed CAR T-Cell Therapy: Trial in ProgressClinically Relevant Abstract

Program: Oral and Poster Abstracts
Session: 704. Cellular Immunotherapies: Early Phase and Investigational Therapies: Poster III
Monday, December 11, 2023, 6:00 PM-8:00 PM

Emily C Liang, MD1,2, Erik L Kimble, MD1,2, Aya Albittar, MD1,2*, Jennifer J. Huang, MD, PhD1,2, Andrew J Portuguese, MD1,2, Aiko Torkelson, BS2*, Delaney Kirchmeier, BS2*, Abigail Chutnik, BS2*, Barbara Pender, MSc2*, Sylvain Simon, PhD3*, Tony Chour, BS1,2*, Evan W. Newell, PhD2*, Rahul Banerjee, MD1,2, David G Maloney, MD, PhD2,4, Alexander Spicer, MSc5*, Juho Jalkanen, MD, PhD5*, Alexandre V Hirayama, MD2,4* and Jordan Gauthier, MD, MSc4,6

1University of Washington, Seattle, WA
2Fred Hutchinson Cancer Center, Seattle, WA
3Translational Science and Therapeutics Division, Fred Hutchinson Cancer Center, Seattle, WA
4Division of Medical Oncology, University of Washington, Seattle, WA
5Faron Pharmaceuticals, Turku, Finland
6Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA


CD19 chimeric antigen receptor (CAR) T-cell therapy has revolutionized the treatment of patients with relapsed/refractory B-cell malignancies. Yet it remains limited by potentially life-threatening toxicities such as CRS and ICANS. The risk of CRS and ICANS restricts the use of CD19 CAR T-cell therapy to large academic centers and leads to high healthcare resource utilization. Current toxicity prevention strategies have shown limited efficacy to date (prophylactic steroids with axi-cel: CRS, 80%; ICANS, 60%; Oluwole, BJH, 2021; early intervention with brexu-cel: CRS, 89%; ICANS, 60%; Shah, The Lancet, 2021). Our group has shown that endothelial activation and dysfunction are associated with the development of CRS and ICANS, suggesting a key role of increased vascular permeability and blood-brain barrier damage in their pathogenesis (Hay, Blood, 2017).

Type-I interferons (IFN-alpha and beta) are major regulators of CD73 expression by endothelial cells, an enzyme critical to the maintenance of endothelial integrity. CD73 breaks down extracellular pro-inflammatory ATP into anti-inflammatory adenosine. In addition, extracellular ATP has been shown to be a major and early driver of systemic inflammation upstream from IL-6 production (Cauwels, Cell Death Dis, 2014), which is associated with severe CRS and ICANS. Preclinical models have demonstrated that IFN-beta-1a treatment is associated with reduced capillary and blood-brain barrier permeability via upregulation of CD73 expression (Floris, J Neuroimmunol, 2002; Kraus., Ann Neurol, 2004; Niemela, Eur J Immunol, 2008). In humans, two recombinant IFN-beta-1a therapies are FDA-approved for the treatment of multiple sclerosis. IFN-beta-1a given intravenously (IV) maximizes the drug’s bioavailability and its protective effects on the endothelium. In a study of patients with ARDS, IV IFN-beta-1a (FP-1201 and FP-1201-lyo) was safe and induced CD73 expression (Bellingan, Lancet Respir Med 2014).

Given the known effects of IFN-beta-1a on preserving endothelial function and blood-brain barrier integrity, we hypothesize that IV IFN-beta-1a (FP-1201) may prevent CRS and ICANS following CD19 CAR T-cell therapy (Figure 1A). Since higher rates of severe CRS and ICANS have been reported after axi-cel and brexu-cel, which contain CD28-costimulatory domains, we will restrict the inclusion criteria to patients treated with these products to analyze a population with a higher unmet need and a more homogeneous risk of CRS/ICANS.


Objectives and endpoints:

  • Primary objective: To evaluate the safety and feasibility of FP-1201 in patients undergoing treatment with axi-cel or brexu-cel with two co-primary endpoints: i) to estimate the incidence of dose-limiting toxicity rates within the first 14 days following the last administration of FP-1201; ii) to study the type, frequency, and severity of adverse events according to the NCI CTCAE v5.0 from the first administration of FP-1201 and until day +28 after CAR T-cell infusion
  • Secondary objectives: i) To decrease the incidence and severity of ICANS; ii) to decrease the incidence and severity of CRS; iii) to decrease corticosteroid usage; iv) to evaluate the effect of FP-1201 on anti-tumor efficacy
  • Exploratory objectives: To characterize the in vivo effects of FP-1201 on endothelial function, the systemic cytokine milieu, and CAR T-cell function

Key inclusion criteria: Adults ≥18 years of age with Karnofsky performance status ≥60% and B-cell non-Hodgkin lymphoma eligible for treatment with axi-cel or brexu-cel

Key exclusion criteria: Known hypersensitivity to IFN-beta or major organ dysfunction

FP-1201 administration: The FDA-approved IFN-beta-1a Rebif® will be formulated for IV administration (FP-1201). Participants will receive FP-1201 at one of four dose levels detailed in Figure 1B.

Statistical design and sample size: We will use a Bayesian Optimal Interval Design to guide the FP-1201 dose escalation. We will plan to treat up to 24 participants.


This is a phase I/II study of IV IFN-beta-1a in preventing CRS and ICANS following axi-cel and brexu-cel. The aim is to demonstrate safety and efficacy and to investigate the biologic mechanisms of IFN-beta-1a in preventing endothelial dysfunction. Additional preclinical and preliminary clinical data will be presented at the meeting. This study is registered on clinicaltrials.gov as NCT05936229.

Disclosures: Kimble: Juno/BMS: Research Funding. Newell: Immunoscape: Current equity holder in private company, Membership on an entity's Board of Directors or advisory committees; Neogene Therapuetics: Current equity holder in private company, Membership on an entity's Board of Directors or advisory committees; Nanostring Technologies: Membership on an entity's Board of Directors or advisory committees. Banerjee: SparkCures: Consultancy; Sanofi: Consultancy; Genentech: Consultancy; Janssen: Consultancy; BMS: Consultancy; Caribou: Consultancy; Pfizer: Consultancy; Pack Health: Research Funding. Maloney: Bioline Rx: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Participation on a Data Safety Monitory Board ; A2 Biotherapeutics: Consultancy, Current holder of stock options in a privately-held company, Honoraria, Other: Member of the Scientific Advisory Board; Amgen: Consultancy, Honoraria; Bristol Myers Squibb: Consultancy, Honoraria, Other: Member of the JCAR017 EAP-001 Safety Review Committee and Member, CLL Strategic Council, Member of the JCAR017-BCM-03 Scientific Steering Committee under BMS, Research Funding; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Participation on a Data Safety Monitory Board , Research Funding; Umoja: Consultancy, Honoraria; Pharmacyclics: Consultancy, Honoraria; Gilead Sciences: Consultancy, Honoraria, Other: Member, Scientific Review Committee, Research Scholars Program in Hematologic Malignancies; Janssen: Consultancy, Honoraria; Incyte: Consultancy, Honoraria; Mustang Bio: Consultancy, Honoraria; Chimeric Therapeutics: Other: Member of the Scientific Advisory Board; MorphoSys: Consultancy, Honoraria; Genentech: Consultancy, Honoraria, Other: Chair and Member of the Lymphoma Steering Committee; ImmPACT Bio: Other: Member, Clinical Advisory Board, CD19/CD20 bi-specific CAR-T Cell Therapy Program; Legend Biotech: Consultancy, Honoraria, Research Funding; Juno Therapeutics: Consultancy, Honoraria, Patents & Royalties: Rights to royalties from Fred Hutch for patents licensed to Juno Therapeutics/BMS, Research Funding; Kite, a Gilead Sciences: Consultancy, Honoraria, Research Funding; Interius: Other: Member, Clinical Advisory Board; Lyell Immunopharma: Other: Member, CAR T Steering Committee; Navan Technologies: Consultancy, Honoraria, Other: Member of the Scientific Advisory Board; Novartis: Consultancy, Honoraria; Fred Hutch: Other: rights to royalties for patents licensed to Juno; Navan Technologies: Current holder of stock options in a privately-held company. Spicer: Faron Pharmaceuticals: Current Employment. Jalkanen: Faron Pharmaceuticals: Current Employment, Current equity holder in publicly-traded company. Hirayama: Novartis: Honoraria; Bristol Myers Squibb: Honoraria, Research Funding; Nektar Therapeutics: Honoraria, Research Funding; Juno Therapeutics, a Bristol Myers Squibb Company: Research Funding. Gauthier: Janssen: Consultancy, Honoraria; Legend Biotech: Consultancy, Honoraria; Kite Pharma: Consultancy, Honoraria; MorphoSys: Consultancy, Research Funding; Angiocrine Bioscience: Research Funding; Century Therapeutics: Other: Independent data review committee; Celgene (a Bristol Myers Squibb company): Research Funding; Juno Therapeutics (a Bristol Myers Squibb company): Research Funding; Sobi: Consultancy, Honoraria, Research Funding.

OffLabel Disclosure: We are studying the safety, feasibility, and efficacy of FP-1201 (intravenous interferon-beta-1a) in preventing CRS and ICANS after CD19 CAR T-cell therapy.

*signifies non-member of ASH