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Background: Currently approved CAR T cell therapies are generally administered as inpatient treatment at university medical centers due to concerns about the frequency, onset, severity, and management of AEs, including cytokine release syndrome (CRS) and neurological events (NEs). Infusion and monitoring of patients who receive CAR T cell therapy at nonuniversity medical centers and in outpatient settings have not been specifically studied. Liso-cel is an investigational, CD19-directed, defined composition, 4-1BB CAR T cell product administered at equal target doses of CD8+ and CD4+ CAR+ T cells. The liso-cel clinical program allows outpatient treatment per investigator discretion, with standardized guidelines for safety monitoring and AE management. Here we present preliminary safety and efficacy outcomes of liso-cel in relapsed/refractory (R/R) aggressive large B-cell lymphoma (LBCL) across inpatient and outpatient settings at nonuniversity medical centers in the OUTREACH study (NCT03744676). Methods: This open-label, multicenter, phase 2 study enrolled adult patients with R/R LBCL at nonuniversity medical centers, including those with university affiliations and centers naïve to CAR T cell therapy. Inclusion criteria included ECOG PS of 0-1, PET-positive disease, adequate organ function, and R/R disease after ≥2 lines of prior systemic therapy including chemoimmunotherapy. Prior autologous HSCT was permitted, but prior allogeneic HSCT was prohibited. After leukapheresis and 3 days of lymphodepleting chemotherapy, patients received liso-cel infusion at a dose of 100 × 106 CAR+ T cells. The primary endpoint was incidence of grade ≥3 CRS, NEs, prolonged cytopenias through day 29, and infections. Secondary endpoints included safety and overall response rate (ORR). All study sites had a multidisciplinary CAR T cell therapy team and standard operating procedures for toxicity monitoring/management of patients treated and/or monitored as outpatients. CRS was graded as per 2014 Lee criteria; NEs were defined as liso-cel-related investigator-assessed events and graded as per NCI CTCAE v4.03. Results: At data cutoff, 34 patients were treated with liso-cel (inpatients, n = 12; outpatients, n = 22); 5 patients were treated at non-Foundation for the Accreditation of Cellular Therapy (FACT)-accredited sites. Demographics and baseline disease characteristics were similar between inpatients and outpatients (Table); overall, median age was 66 years (range, 34-83), 68% had diffuse LBCL not otherwise specified, and 88% were refractory to last therapy. CRS was reported in 4 inpatients (33%) and 9 outpatients (41%), with no grade ≥3 events. NEs were reported in 3 inpatients (25%) and 6 outpatients (27%), with 1 grade 3 event in the outpatient group. Median (range) time to onset of CRS and NEs, respectively, was 2.5 (1-3) and 10 (5-16) days for inpatients and 6 (2-9) and 8.5 (6-13) days for outpatients. Tocilizumab and/or corticosteroid use for CRS and/or NE management was generally low (inpatients, n = 2 [17%]; outpatients, n = 5 [23%]). Overall, the most common (≥45%) treatment-emergent AEs (TEAEs) were neutropenia (76%), leukopenia (50%), and anemia (47%). Prolonged cytopenias (grade ≥3 lab values at Day 29) were reported for 7 (21%) patients. No grade 5 TEAEs were reported. Early (≤ study Day 4) and overall hospitalization in outpatients was 18% and 50%, respectively; median time to hospitalization was 5 (2-9) days and median length of stay was 6 (1-18) days. Among efficacy-evaluable patients (n = 31), ORR was 75% for inpatients and 84% for outpatients; CR rate was 50% and 68%, respectively. Of the 5 patients treated at non-FACT-accredited sites (inpatients, n = 1; outpatients, n = 4), 2 had CRS and/or NEs, but none were grade ≥3 events; none of these patients received tocilizumab or corticosteroids. Of these 5 patients, 1 achieved CR and 1 achieved PR; 2 had stable disease and 1 had progressive disease. Conclusions: Patients with R/R aggressive LBCL were successfully treated with liso-cel and monitored for CAR T cell therapy-related toxicities at nonuniversity medical centers in inpatient and outpatient settings using standard operating procedures and multidisciplinary teams. Incidences of severe CRS and NEs were low, as was tocilizumab and/or corticosteroid use. Liso-cel showed encouraging preliminary efficacy in both inpatients and outpatients. This trial is ongoing and actively recruiting. Disclosures Freytes: Sanofi: Speakers Bureau. Stevens:Amgen, MorphoSys: Consultancy. Varela:Neximmune: Consultancy, Current equity holder in private company. Cherry:Kite: Other: Ad Board; Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees, Other: Ad Board; Epizyme: Other: Ad Board . Essell:Kite: Speakers Bureau; Bristol Myers Squibb: Speakers Bureau. Courtright:AbbVie: Other: Investigator in AbbVie-sponsored clinical trials.. Fanning:Takeda: Consultancy, Speakers Bureau; Abbvie: Consultancy; Sanofi Aventis: Speakers Bureau; TG Therapeautics: Consultancy; Bristol Myers Squibb: Consultancy, Speakers Bureau; Prisma Health: Current Employment. Yimer:Sanofi: Speakers Bureau; AstraZeneca: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company), Speakers Bureau; Janssen: Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company), Research Funding, Speakers Bureau; BeiGene: Other: TRAVEL, ACCOMODATIONS, EXPENSES (paid by any for-profit health care company), Research Funding, Speakers Bureau; Epizyme: Consultancy, Divested equity in a private or publicly-traded company in the past 24 months; Karyopharm: Consultancy, Divested equity in a private or publicly-traded company in the past 24 months, Membership on an entity's Board of Directors or advisory committees, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company), Speakers Bureau; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company), Speakers Bureau; Celgene, a Bristol-Myers Squibb Company: Consultancy, Membership on an entity's Board of Directors or advisory committees; Takeda: Speakers Bureau; TG Therapeutics: Consultancy; Texas Oncology: Current Employment. Trede:Juno Therapeutics, a Bristol-Myers Squibb Company: Current Employment; Bristol-Myers Squibb Company: Current equity holder in publicly-traded company. Youssef:Bristol-Myers Squibb Company: Current Employment, Current equity holder in publicly-traded company. Lymp:Juno Therapeutics, a Bristol-Myers Squibb Company: Current Employment; Bristol-Myers Squibb Company: Current equity holder in publicly-traded company. Bachier:Juno Therapeutics, a Bristol-Myers Squibb Company: Honoraria; CRISPR: Honoraria; AlloVir: Honoraria; Sanofi: Speakers Bureau.

Background: CAR T cell therapies are generally administered in an inpt setting owing to concerns of AE management. Infusion and monitoring of pts who receive CAR T cell therapy at nonuniversity medical centers (NMC) and in outpt settings have not been studied specifically. Liso-cel is an autologous CD19-directed, defined composition, 4-1BB CAR T cell product administered at equal target doses of CD8 + and CD4 + CAR + T cells. In TRANSCEND NHL 001 (NCT02631044) in pts with third- or later-line LBCL, liso-cel treatment showed an ORR of 73% (CR rate, 53%), with grade ≥ 3 cytokine release syndrome (CRS) in 2%, and grade ≥ 3 neurological events (NE) in 10% of pts (Abramson et al. Lancet 2020). We report outcomes of liso-cel in pts with R/R LBCL across inpt and outpt settings at NMCs in the United States treated in the OUTREACH study (NCT03744676). Methods: The study enrolled pts at NMCs, including those with university affiliations and centers naïve to CAR T cell therapy. Adults with R/R PET-positive LBCL after ≥ 2 lines of therapy and ECOG PS ≤ 1 were eligible. Pts with grade 3-4 cytopenias, mild to moderate organ function (LVEF ≥ 40%; serum CrCl > 30 mL/min), secondary CNS lymphoma, and prior autologous HSCT were eligible. After leukapheresis and lymphodepleting chemotherapy (LDC), pts received liso-cel at a target dose of 100 × 10 6 CAR + T cells. Primary endpoint was incidence of grade ≥ 3 CRS, NEs, prolonged cytopenias (Day 29 grade ≥ 3 lab values), and infections. Secondary endpoints included safety, ORR, CR rate, duration of response (DOR), and liso-cel PK. B-cell depletion analyses were exploratory. AEs, including NEs, were graded using NCI CTCAE v4.03; CRS was graded per Lee criteria (2014). NEs were defined as investigator-identified neurological AEs related to liso-cel. All study sites had a multidisciplinary CAR T cell therapy team and standard operating procedures (SOP) for outpt monitoring of toxicity and admission for CRS/NE management. Results: At data cutoff, 71 pts were treated with liso-cel at NMCs; 52 and 19 were monitored as outpts and inpts, respectively. Median age was 65 years (range, 28-83; ≥ 65 years, 51%; ≥ 75 years, 18%); 65% of pts had de novo DLBCL, 68% had screening ECOG PS of 1, 82% were chemotherapy refractory, 31% had ≥ 3 prior therapies, and 48% had markers of high tumor burden (pre-LDC LDH ≥ 500 U/L or SPD ≥ 50 cm 2). Demographics and baseline disease characteristics were generally similar in outpts and inpts, respectively, with differences of ≥ 20% noted in incidences of high-grade B-cell lymphoma (4% vs 42%) and DLBCL transformed from indolent lymphoma (29% vs 0%). Overall, any-grade CRS occurred in 39% of pts (no grade ≥ 3) and NEs in 32% (grade 3-4, 10%); 27% received tocilizumab and/or corticosteroids for CRS or NEs. Incidences of any-grade CRS and NEs were similar in outpts and inpts, while grade ≥ 3 NEs, infections, and prolonged cytopenias were numerically higher in outpts, but similar to pivotal trial observations (Table). The most common treatment-emergent AEs were neutropenia (68%), leukopenia (45%), CRS (39%), anemia (38%), thrombocytopenia (37%), and fatigue (35%). No grade 5 AEs were reported. Early (study Day ≤ 4) and overall hospitalization occurred in 33% and 69% of outpts, respectively; median time to hospitalization was 5.0 days (range 2-141) in outpts. The median (range) length of initial hospital stay after liso-cel administration was 6.0 days (1-28; n = 36) for outpts versus 10.0 days (0-31; n = 19) for inpts; 31% of outpts were not hospitalized. All pts were efficacy evaluable. The ORR was 77% and the CR rate was 51%. Median DOR was 14.8 months (95% CI, 3.9‒not reached [NR]) for outpts and was NR (95% CI, 2.0‒NR) for inpts at a median follow-up of 8.1 months and 11.3 months, respectively (Table). PK profiles were similar in outpts and inpts. Target depletion of CD19 + B cells in peripheral blood was also similar between oupts and inpts, and was maintained over the period of 1 year. Conclusions: Pts with R/R LBCL were successfully treated with liso-cel in outpt and inpt settings at NMCs and monitored for CAR T cell therapy-related toxicities using SOPs and multidisciplinary teams. Liso-cel demonstrated durable clinical activity with a favorable safety profile in both outpts and inpts. Incidences of severe CRS and NEs were low, as was tocilizumab and/or corticosteroid use. These data support liso-cel administration at NMCs and in the outpt setting. Figure 1 Figure 1. Disclosures Bachier: Novartis: Membership on an entity's Board of Directors or advisory committees; Mana: Membership on an entity's Board of Directors or advisory committees; Nkarta: Membership on an entity's Board of Directors or advisory committees; Autolus: Membership on an entity's Board of Directors or advisory committees; CRISPR: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees. Varela: Kite: Speakers Bureau; Nexlmmune: Current equity holder in publicly-traded company, Honoraria, Membership on an entity's Board of Directors or advisory committees. Cherry: BMS: Membership on an entity's Board of Directors or advisory committees; Genetech: Membership on an entity's Board of Directors or advisory committees; Jazz: Membership on an entity's Board of Directors or advisory committees. Fanning: Sanofi: Speakers Bureau; Takeda: Speakers Bureau; ADC Therapeutics: Membership on an entity's Board of Directors or advisory committees; Genmab: Membership on an entity's Board of Directors or advisory committees; TG Pharma: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BMS: Speakers Bureau; Genentech: Membership on an entity's Board of Directors or advisory committees. Essell: Gilead: Current Employment, Speakers Bureau; BMS: Speakers Bureau. Yimer: Texas Oncology: Current Employment; Pharmacyclics: Speakers Bureau; Amgen: Speakers Bureau; Sanofi: Speakers Bureau; GSK: Speakers Bureau; Beigene: Speakers Bureau; Janssen: Speakers Bureau; Astrazeneca: Speakers Bureau; Karyopharm: Current equity holder in publicly-traded company, Speakers Bureau. Sharman: AstraZeneca: Consultancy; AbbVie: Consultancy; BMS: Consultancy; TG Therapeutics: Consultancy; Centessa: Current holder of stock options in a privately-held company, Membership on an entity's Board of Directors or advisory committees; BeiGene: Consultancy; Pharmacyclics LLC, an AbbVie Company: Consultancy; Lilly: Consultancy. Espinola: BMS: Current Employment, Current equity holder in publicly-traded company. Mailley: BMS: Current Employment, Current equity holder in publicly-traded company. Avilion: BMS: Current Employment, Current equity holder in publicly-traded company. Ogasawara: Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Ou: BMS: Current Employment. Shaughnessy: Sanofi: Honoraria, Speakers Bureau; Kite: Honoraria, Speakers Bureau; BMS: Honoraria, Speakers Bureau.

CAR-T therapies represent a novel advance in oncology, albeit at list prices that exceed $373,000 (and that does not capture their total cost to the healthcare system). Since initial product approval in 2017, stakeholders and observers have attempted to investigate clinical and financial impacts of CAR-T therapies, and potential approaches to optimizing access and use by eligible patients. Most existing research is from a single stakeholder perspective - patients, providers, or payers - limiting the ability to draw broader conclusions on trends and offer prospective recommendations. To address this knowledge gap, we sought to identify and describe critical success factors for optimal delivery of CAR-T therapies. We undertook a qualitative study based on interviews with multiple US-based stakeholders including clinicians, financial and operations staff, and payer-insurers. Interviewees--which included oncologists (n=6), facility financial and operational personnel (n=4), and coverage and reimbursement decision-makers from US health plans (n=3)--completed structured, live, hour-long, interviews covering clinical, administrative, and general topics on patient access to CAR-T therapies. All clinicians had experience with ≥1 FDA-approved CAR-T therapies in both registered clinical trials and clinical practice; financial and operational personnel were affiliated with the same facilities as the clinicians, and also had real-world experience with these therapies; payer representatives were directors from a large national commercial plan, regional integrated delivery network, and a Medicare administrative contractor, respectively. Consensus facility feedback (i.e., clinicians, operational personnel) was that CAR-T is effective, and that their administrative processes had been optimized through care team coordination and experience-based efficiencies; in contrast, 2 of 3 payer interviewees expressed that, while CAR-T therapies have shown efficacy, their real-world benefits and applicability are less well-defined. Facility interviewees noted that: (1) reimbursement from commercial insurers is higher than from Medicare, with the latter associated with per-patient net-neutral or negative margins; (2) when possible, differential reimbursement between inpatient and outpatient settings may drive patient management towards outpatient care; and (3) negative-margin cases are currently deemed acceptable due to nonclinical factors (i.e., competitive pressure within a geographic region, anticipated branding/marketing value) and relatively small treated populations. From payer interviewees, CAR-T cost and perceived cost-to-value have made health plans more receptive to considering outcomes-based contracting, capitated provider payments, or other mitigation methods. Left unoptimized, these factors may adversely impact patient access to, and long-term provider attractiveness of, CAR-T therapies. All interviewees agreed that as the CAR-T marketplace grows, a strong preference exists for manufacturers to develop and communicate for their therapies durable outcomes data, clear and comprehensive reimbursement information, and competitive pricing. With the potential for many approved products in a single indication, and/or a single approval for indications with relatively large eligible patient populations, interviewees also conveyed interest in compelling health economic data. Facility interviewees also acknowledged that if it remains an overall net-negative margin service, new providers will be less able to start CAR-T programs and smaller programs may encounter sustainability issues, collectively jeopardizing patient access to these life-changing therapies. Overall, findings from this study suggest that during the continued maturation of the landscape, stakeholders will need to be proactive to ensure that CAR T-cell therapies can be maintained amidst financial and operational pressures. Several CAR-T therapy options for multiple myeloma are on the immediate horizon, likely increasing demand among eligible patients. Accordingly, the need to link real-world evidence of the clinical value and institutional investment burden of these therapies to reimbursement is imperative, both to insulate payers and enable clinicians to provide innovative therapies. Figure 1 Figure 1. Disclosures Faber: Amgen: Honoraria; Adaptive: Honoraria; Cardinal Health: Honoraria; Celgene: Honoraria; Astra Zeneca: Honoraria; GlaxoSmith Kline: Honoraria; Janssen: Honoraria; Juno: Honoraria; Karyopharm: Honoraria; Kite: Honoraria; Takeda: Honoraria; Sanofi Genzyme: Honoraria. Hunter: BMS: Consultancy, Honoraria; Kite: Consultancy, Honoraria, Speakers Bureau; Novartis: Consultancy, Honoraria. Deol: Kite, a Gilead Company: Consultancy. Crivera: Johnson & Johnson: Current Employment, Current equity holder in publicly-traded company. Riccobono: Legend Biotech: Current Employment, Current holder of individual stocks in a privately-held company, Current holder of stock options in a privately-held company. Garrett: Legend Biotech USA: Current Employment. Jackson: Memorial Sloan Kettering Cancer Center: Consultancy; Janssen: Current Employment. Fowler: Amgen: Ended employment in the past 24 months; Janssen: Current Employment. Berger: Janssen Scientific Affairs: Consultancy, Research Funding. Lorden: Janssen Scientific Affairs: Consultancy, Research Funding. Stewart: Janssen Scientific Affairs: Consultancy, Research Funding.

Introduction Clinical decision support (CDS) technology has the potential to improve health outcomes by offering physicians an informational resource to support review and application of best pratices.1 The Multiple Myeloma Research Foundation (MMRF) and Intermountain Healthcare (IMH) conducted a study to assess the suitability of a single health system's data for a myeloma-specific CDS tool that visualizes treatment pathways, and to assess the effort needed to support a CDS program.2 This research is part of a longer-term effort to explore how CDS technology can help: - increase awareness of and apply treatment guidelines by visualizing pathways for specific MM patient cohorts - improve understanding of treatment variation within health systems - improve outcomes research by showing relationships between treatments and outcomes Methods IA12 data from the CoMMpass study3 was used to create a CDS tool prototype. These data were aggregated into state and transition maps to identify nodes and pathways with corresponding outcomes, including response, progression-free survival (PFS), and overall survival (OS). Intervening patient states were displayed using Sankey diagrams [Fig. 1]. We also tested if EMR data from a community health system (i.e., IMH) could support such visualization. The team designed a study protocol and obtained IRB approval. Inclusion criteria included patients with active MM between January 2016-June 2018; adult aged 18 years to 89 years at diagnosis of active or smoldering MM. An IMH-specific data dictionary was assessed for variable importance, quantity, and ease of acquisition. [Table 1]. IMH then manually abstracted prioritized structured (eg: labs) and non-structured (eg: notes) data for use in the tool. Results Ninety-six of an initial 146 patients meeting eligibility criteria had sufficient data usable for the study, reflecting 44 unique drug combinations across 9 lines of therapy. The tool was able to associate and visualize all patients and their clinical states and transitions to their outcomes. Clinical data was typically complete (99% of the time), including key clinician-derived data, such as ECOG scores (78%) and treatment response (99%). 569 person-hours were required to conduct the abstraction activity on 96 cases, averaging 5.9 hours/patient Discussion The IMH portion of the study supports the hypothesis that a community health system can provide sufficient high-quality information to power a CDS tool with priority features. Only 65% (96/146) of the initial study group had usable data because some patients had received partial care outside of the IMH integrated delivery network (IDN) leaving associated data inaccessible. Initial biostatistical analysis suggests that roughly 750-1000 complete patient records would be required for statistically significant outcomes research with granularly stratified cohorts. The MMRF is currently recruiting 5-7 additional large IDNs to obtain the patients to power more generalizable functionality. References 1 McKie PM, Kor DJ, Cook DA, Kessler ME, Carter RE, Wilson PM, et al. Computerized advisory decision support for cardiovascular diseases in primary care: a cluster randomized trial. Am J Med [Internet]. 2019 Dec 18 [cited 2020 Mar 5]. Available from: https://doi.org/10.1016/j.amjmed.2019.10.039 2 Garcelon N, Burgun A, Salomon R, Neuraz A. Electronic health records for the diagnosis of rare diseases. Kidney Int [Internet]. 2020 Jan 14 [cited 2020 Mar 5]. Available from: https://doi.org/10.1016/ j.kint.2019.11.037 3 Christofferson A, Nasser S, Aldrich J, Penaherrera D, Legendre C, Benard B, et al. Integrative analysis of the genomic landscape underlying multiple myeloma at diagnosis: an Mmrf Commpass analysis. Blood. 2017 Dec 7; 130 (Supplement 1): 326. Disclosures No relevant conflicts of interest to declare.

Background: Acute graft versus host disease (aGVHD) occurs in approximately 50% of patients receiving allogeneic hematopoietic stem cell transplant (HSCT) with standard GVHD prophylaxis regimens and is a significant contributor to morbidity and non-relapse mortality (NRM). There are currently no FDA approved therapies for the initial treatment of newly diagnosed aGVHD. T effector cells (Teff), particularly CD4+ T helper cells, play a central role in the pathogenesis of aGVHD. CD6 is a co-stimulatory receptor, predominantly expressed on CD4+ T helper cells, that binds to activated leukocyte cell adhesion molecule (ALCAM), a ligand expressed on antigen presenting cells and various epithelial and endothelial tissues. The CD6-ALCAM pathway plays an integral role in modulating T cell activation and trafficking and is central to immune mediated inflammation. Previous studies by Soiffer et al. in patients receiving allogeneic bone marrow transplants had shown that depleting CD6+ T cells ex-vivo in donor bone marrow using T-12, an anti-CD6 monoclonal antibody (mAb), as a sole method for GVHD prophylaxis lowered the incidence of acute and chronic GVHD. EQ001 (itolizumab) is a humanized IgG1 mAb that binds to CD6 and blocks the interaction with ALCAM and inhibits both the activity and trafficking of T cells without causing T cell depletion. Itolizumab has s previously been developed and is approved for the treatment of Psoriasis in India. The potential effectiveness of an anti-CD6 mAb targeted approach in treating aGVHD is supported by data from pre-clinical models evaluating the prevention and treatment of GVHD with EQ001. The objective of this study is to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and clinical activity of EQ001 in subjects with newly diagnosed aGVHD. Study Design and Methods: This is a multi-center Phase 1b/2 study (NCT03763318) of EQ001 in subjects with aGVHD. Part A (Phase 1b) of the study is an open-label, multiple ascending dose study of EQ001 in adults with newly diagnosed High Risk (MacMillan Criteria) aGVHD following HSCT. Approximately 24 subjects will be enrolled in successive cohorts of 3 to 6 adult subjects using a standard 3 + 3 dose escalation design. For each cohort, subjects will receive EQ001 administered intravenously (IV) every two weeks for five doses with corticosteroids (CS) tapered over the treatment period. A total of four dose levels will be tested ranging from 0.4 mg/kg to 2.4 mg/kg, and subjects will be followed for an additional 10 months after study treatment is completed. The primary objective of Part A is to evaluate safety and tolerability of EQ001. Secondary objectives include an evaluation of PK, PD (including CD6 receptor occupancy, changes in inflammatory cytokines and novel gut biomarkers [ST2, REG3α], and changes in Teff/T regulatory cells populations), and clinical activity (overall aGVHD response rates on Day 29, durability of the response at Day 57 and up to 1 year, cumulative incidence of NRM, rates of chronic GVHD, and CS dose requirements). Data from Part A will inform the dose selection for Part B (Phase 2) of the study. Enrollment to Part A is ongoing. Part B is a double-blind, placebo-controlled study in subjects (age ≥12) with newly diagnosed Grade II-IV aGVHD. Approximately 60 subjects will be randomized in a 2:1 ratio to either treatment with EQ001 (n=40) or placebo (n=20) in addition to and within 72 hours of the first dose of CS. EQ001 or placebo will be administered IV every two weeks for five doses, and subjects will be followed for an additional 10 months after the last dose of study treatment. The primary objective of Part B is to evaluate the overall response rate of aGVHD in patients treated with EQ001 versus placebo. Secondary objectives include an evaluation of safety and other clinical endpoints. The primary endpoint is the overall response rate at Day 29 as defined by a complete response, very good partial response or partial response. Additional clinical endpoints include assessment of NRM, chronic GVHD rates, and CS dose requirements. Conclusion: Inhibiting the CD6-ALCAM pathway with EQ001 represents a unique and promising approach for the treatment of aGVHD following HSCT by inhibiting both the activity and trafficking of T cells. This is the first clinical study to examine the effects of an anti-CD6 therapy for the treatment of patients with newly diagnosed aGVHD. Disclosures Koreth: Equillium: Consultancy; Cugene: Consultancy; Amgen: Consultancy. Shea:Jazz: Consultancy; Amgen: Consultancy; Merck: Consultancy. Jagasia:Kadmon: Consultancy; Incyte: Consultancy; Janssen: Research Funding. Waller:Pharmacyclics: Other: Travel expenses, Research Funding; Cerus Corporation: Other: Stock, Patents & Royalties; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Chimerix: Other: Stock; Cambium Oncology: Patents & Royalties: Patents, royalties or other intellectual property ; Amgen: Consultancy; Kalytera: Consultancy. Nakamura:Celgene: Other: support for an academic seminar in a university in Japan; Merck: Membership on an entity's Board of Directors or advisory committees; Alexion: Other: support to a lecture at a Japan Society of Transfusion/Cellular Therapy meeting ; Kirin Kyowa: Other: support for an academic seminar in a university in Japan. Ng:Equillium: Employment, Equity Ownership. Sonnemann:Equillium Inc.: Employment. Light:Equillium Inc.: Consultancy. Nanayakkara:Equillium Inc.: Consultancy. Essayan:Equillium Inc.: Consultancy. Rothman:Equillium Inc.: Employment, Equity Ownership. Connelly:Equillium: Employment, Equity Ownership. Polu:Equillium Inc.: Employment, Equity Ownership. Kean:HiFiBio: Consultancy; BlueBirdBio: Research Funding; Gilead: Research Funding; Regeneron: Research Funding; EMDSerono: Consultancy; FortySeven: Consultancy; Magenta: Research Funding; Kymab: Consultancy; Jazz: Research Funding; Bristol Meyers Squibb: Patents & Royalties, Research Funding. Ritz:Draper Labs: Consultancy; Talaris Therapeutics: Consultancy; TScan Therapeutics: Consultancy; Equillium: Research Funding; Merck: Research Funding; Kite Pharma: Research Funding; Aleta Biotherapeutics: Consultancy; Celgene: Consultancy; Avrobio: Consultancy; LifeVault Bio: Consultancy. Soiffer:Gilead, Mana therapeutic, Cugene, Jazz: Consultancy; Juno, kiadis: Membership on an entity's Board of Directors or advisory committees, Other: DSMB; Kiadis: Other: supervisory board; Mana therapeutic: Consultancy; Cugene: Consultancy; Jazz: Consultancy. Cutler:Kadmon: Consultancy; Omeros: Consultancy; ElsaLys: Consultancy; BiolineRx: Other: DSMB; Cellect: Other: DSMB; Kalytera: Other: DSMB; Incyte: Consultancy; Genentech: Consultancy; Jazz: Consultancy; BMS: Consultancy; Fate Therapeutics: Consultancy; Pharmacyclics: Consultancy. OffLabel Disclosure: EQ001 (itolizumab) is an investigational agent being developed for the treatment of acute GVHD. Itolizumab has not received regulatory approval for the treatment of GVHD. The abstract being submitted describes the study design for the phase 1b/2 study. No data is being presented.

Abstract 2235 Poster Board II-212 Acute graft-versus-host disease (aGVHD) remains the major cause of morbidity and mortality in allogeneic hematopoietic cell transplant recipients. There is no consensus in regards to the best therapy for patients who fail to respond to, or do not tolerate, systemic glucocorticoids. We evaluate the efficacy of sirolimus in 34 pts, median age of 49 (23-67) years, with steroid-refractory (N=31) or steroid-intolerant (N=3) aGVHD. The diagnosis of aGVHD was established at a median of 34 (7-1042) days after transplantation, and confirmed by biopsy in all cases. Initial treatment of aGVHD consisted of prednisone up to 2 mg/kg. Sirolimus was initiated at a median of 9 (1-255) days after glucocorticoid initiation. A loading dose of sirolimus was administered to 19 (56%) of 34 pts, median 6 (3-8) mg, followed by maintenance therapy of 1-2 mg per day with doses adjusted to target therapeutic trough levels between 4 and 12 ng/ml; therapeutic levels were achieved in all cases. The overall response rate was 76%. Fifteen (44%) of the 34 pts achieved a CR after sirolimus initiation and without requiring additional immune suppressive agents. CR was achieved in 11/31 (42%) steroid-refractory patients, and in 2/3 (67%) steroid-intolerant patients. The median overall survival (OS) after initiation of sirolimus was 5.6 months, and one year OS was 44% (95% C.I. 27%-60%). Maximum decrease in dose of steroids over 12 weeks following sirolimus was a median of 50% (range 0-100%). Fourteen (42%) of 33 pts reached a dose < 20 mg of prednisone at a median of 4 months (95% CI: 3.5-13.5) after initiation of sirolimus. Seven (21%) of 34 pts were free from steroids after a median of 20 months (95% CI: 9.2-20.0) after initiation of sirolimus. Two pts were shown to be successfully liberated from all immunosuppressive agents without recurrent GVHD at 2.7 and 7.1 months after initiation of sirolimus, respectively. These data indicate the sirolimus is effective in controlling steroid-refractory aGVHD. Further studies are needed to determine the most appropriate timing for sirolimus after transplantation, whether prophylaxis, primary or secondary GVHD therapy. Disclosures: Off Label Use: Sirolimus for graft-versus-host disease.