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Introduction: Chronic graft-versus-host disease (cGVHD) is a common complication post allogeneic hematopoietic cell transplant. The goal of cGVHD treatment is symptom relief and long-term control of disease progression, with minimal toxicity/adverse events. Available treatments, including corticosteroids, mTOR inhibitors, calcineurin inhibitors, extracorporeal photopheresis, mycophenolate mofetil, ibrutinib, and ruxolitinib, are associated with adverse events (AEs) that may limit compliance or lead to treatment discontinuation. Belumosudil is a selective Rho-associated coiled-coil kinase 2 (ROCK2) inhibitor that is approved for the treatment of cGVHD for adult and pediatric patients 12 years and older after failure of at least two prior lines of systemic therapy (i.e., 3L/4L+). Belumosudil has been well tolerated in clinical trials, with a low incidence of grade ≥3 AEs, including cytopenias and infections, which may lead to increased compliance to treatment and lower overall costs. The present analysis estimated the budget impact of increasing utilization of belumosudil in 3L/4L+ cGVHD in three scenarios using a United States (US) payer perspective. Methods: A 5-year budget impact model was developed to estimate annual healthcare resources utilization (HCRU) and budget impact for a 10 million member US payer plan. Epidemiology, market share, treatment cost, adverse events, and HCRU inputs were incorporated in the model in a user-modifiable manner. US cGVHD prevalence rates were incorporated based on literature and secondary sources (Bachier et al. 2021). In addition to belumosudil, treatments that can potentially be accounted for in the model include corticosteroids, calcineurin inhibitors, mTOR inhibitors, mycophenolate mofetil, extracorporeal photopheresis, ibrutinib, and ruxolitinib (off-label), with proportions based on current and projected market share. Belumosudil use was modeled in three different scenarios based on projections of branded agent shares (i.e., source of share from ibrutinib only, ruxolitinib only, or both ibrutinib and ruxolitinib in a market with branded agents only). Grade 3/4 adverse events and their rates in cGVHD were sourced from prescribing information, clinical trials, or published literature and were monetized using Medicare Diagnosis Related Groups costs, with conversion to commercial plan costs utilizing ratios from the Congressional Budget Office. Drug costs were sourced from Redbook. HCRU and costs per visit were derived from a prior cGVHD claims analysis. The overall percentage reduction and per member per month (PMPM) savings were calculated. Results: When belumosudil share is taken only from ibrutinib, by 2026, the model estimates a 0.9% reduction in the plan's budget and a PMPM savings of $0.01 versus a market without belumosudil. Percentage cost offsets due to reductions in AE and HCRU costs with belumosudil adoption were 34.3% and 13.5%, respectively. In a scenario where belumosudil share is taken only from ruxolitinib, an estimated reduction in budget of 1.9% and a savings of $0.01 PMPM would be observed by 2026, largely due to cost reductions of 76.2% and 27.9% in AEs and HCRU, respectively. If belumosudil share is derived from both ibrutinib and ruxolitinib similar results were observed, with a 1.9% reduction in budget and $0.01 in PMPM savings by 2026. AE and HCRU cost reductions versus a scenario without belumosudil were 71.2% and 27.7%, respectively. Conclusions: The introduction of belumosudil as a therapy for 3L/4L+ cGVHD patients resulted in a budget reduction in this model for US health plans. In each of the three scenarios examined, focusing on patients receiving existing branded agents in 3L/4L+ cGHVD, belumosudil demonstrated 0.9-1.9% in overall and $0.01 in PMPM savings, likely driven by the favorable safety profile of belumosudil reducing AEs and HCRU. The model indicates that belumosudil may provide an alternative to existing cGVHD treatments while also offering cost savings to a US health plan. Patients who enter 3L/4L+ cGVHD treatment may benefit from recently approved therapies for cGVHD like belumosudil that offer a well tolerated treatment option for patients who are cycling through cGVHD therapies. Figure 1 Figure 1. Disclosures Bachier: BMS: Membership on an entity's Board of Directors or advisory committees; CRISPR: Membership on an entity's Board of Directors or advisory committees; Autolus: Membership on an entity's Board of Directors or advisory committees; 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. Skaar: Trinity Life Sciences: Current Employment; Kadmon Corporation: Consultancy. Dehipawala: Trinity Life Sciences: Current Employment; Kadmon Corporation: Consultancy. Miao: Trinity Life Sciences: Current Employment; Kadmon Corporation: Consultancy. Ieyoub: Kadmon Corporation: Current Employment. Taitel: Kadmon Corporation: Current Employment.

Introduction: Belumosudil (KD025) is a novel oral selective rho-associated coiled-coil kinase 2 (ROCK2) inhibitor specifically designed for the treatment of cGVHD, an immune-mediated inflammatory and fibrotic disorder. In a previous dose-finding study (KD025-208, N=54), two-thirds of patients, including those with fibrotic and inflammatory manifestations, achieved a partial or complete response with belumosudil. Herein, we report on the top-line results (6 months after the last patient in) from the pivotal phase 2 trial (ROCKstar [KD025-213], N=132). Methods: This phase 2, open-label, randomized, multicenter study evaluated belumosudil 200 mg QD (n=66) and BID (n=66) in patients with cGVHD who received 2 to 5 prior lines of therapy (LOT). Treatment continued until clinically significant progression of cGVHD. The primary end point was overall response rate (ORR), defined per the 2014 National Institutes of Health Consensus Criteria. Additional end points included duration of response (DOR), Lee Symptom Scale (LSS) score, failure-free survival (FFS), corticosteroid (CS) dose reductions and overall survival. The study was powered such that the lower bound of the 95% confidence interval (CI) excludes 30%, with appropriate multiplicity adjustment. Results: At enrollment, the median age was 56 years, the median time from cGVHD diagnosis to enrollment was 29 months, 67% of patients had severe cGVHD, 52% had ≥4 organs involved, 72% had received ≥3 prior LOT (including ibrutinib [n=46] or ruxolitinib [n=38]) and 73% were refractory to their last LOT. The baseline characteristics of both arms were well balanced. With a median follow-up of 8 months, the ORR (95% CI) with belumosudil 200 mg QD and BID was 73% (60%-83%) and 74% (62%-84%), respectively (Table 1). In patients who previously received ruxolitinib (29%), the ORR with belumosudil 200 mg QD and BID was 65% (41%-85%) and 72% (47%-90%), respectively. In patients who previously received ibrutinib (35%), the ORR with belumosudil 200 mg QD and BID was 73% (50%-89%) and 71% (49%-87%), respectively. High ORRs were seen in all patient subgroups, regardless of length of time from diagnosis to treatment, including those with severe cGVHD, involvement of ≥4 organs and a refractory response to prior LOT (Figure 1). The response rate was similar across all affected organs. The median time to response was 4 weeks. Of responders, 49% have maintained response for ≥20 weeks. The median DOR has not yet been reached. Clinically meaningful improvement (≥7-point reduction) in LSS score on consecutive assessments was observed in 39% and 33% of patients in the QD and BID groups, respectively. Both responders (43%) and nonresponders (17%) experienced a clinically meaningful improvement in LSS score. FFS was 77% (69%-84%) at 6 months. CS and calcineurin inhibitor discontinuations were seen in 18% and 13% of patients, respectively. Belumosudil was well tolerated, with >95% relative dose intensity in 83% of patients. Drug discontinuation occurred in 10% of patients due to possible drug-related adverse events (AEs), 3% due to progression of underlying disease and 12% due to progression of cGVHD. AEs were consistent with those expected in patients with cGVHD receiving CS and other immunosuppressants (Table 2). Common AEs included fatigue (32%), diarrhea (29%), nausea (26%), cough (24%), dyspnea (24%), upper respiratory tract infection (23%), peripheral edema (21%) and headache (20%). At least 1 serious AE occurred in 34% of patients. Twenty-three percent of patients had at least 1 liver-related investigation; the most common was increased gamma-glutamyltransferase (11%), and only 1 patient showed an increase in bilirubin. Eight patients died during the study; 5 due to AEs (1 possibly related to belumosudil) and 3 during long-term follow-up (>28 days after last dose). There were no reports of cytomegalovirus reactivation or infection. Conclusion: Treatment with belumosudil at both doses resulted in high ORRs across key subgroups, meeting the primary end point of this pivotal randomized trial in cGVHD. Responses were durable and clinically meaningful, irrespective of patient and cGVHD characteristics, and were seen in patients who previously received ruxolitinib and ibrutinib. Belumosudil was well tolerated, with limited and manageable AEs. Further studies will evaluate its use earlier in disease management. The 12-month data analysis will be presented at ASH 2020. Download : Download high-res image (508KB) Download : Download full-size image Disclosures Cutler: Incyte: Consultancy, Membership on an entity's Board of Directors or advisory committees; Kadmon: Consultancy, Membership on an entity's Board of Directors or advisory committees; Jazz: Consultancy, Membership on an entity's Board of Directors or advisory committees; Medsenic: Consultancy, Membership on an entity's Board of Directors or advisory committees; Generon: Consultancy, Membership on an entity's Board of Directors or advisory committees; Mesoblast: Consultancy, Membership on an entity's Board of Directors or advisory committees. Lee: Pfizer: Consultancy, Research Funding; Incyte: Consultancy, Research Funding; Amgen: Research Funding; Kadmon: Research Funding; AstraZeneca: Research Funding; Novartis: Research Funding; Takeda: Research Funding; Syndax: Research Funding. Rotta: Merck: Speakers Bureau; Jazz Pharma: Speakers Bureau. Ramakrishnan: Amgen: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Cigna: Honoraria. Eiznhamer: Kadmon Corporation, LLC: Current Employment, Current equity holder in publicly-traded company. Schueller: Kadmon Corporation, LLC: Current Employment, Current equity holder in publicly-traded company. Yang: Kadmon Corporation, LLC: Current Employment, Current equity holder in publicly-traded company. Green: Kadmon Corporation, LLC: Current Employment, Current equity holder in publicly-traded company. Aggarwal: Kadmon Corporation, LLC: Consultancy; Angiocrine Bioscience, Inc: Current Employment, Other: stock options. Blazar: BlueRock Therapeutics: Research Funding; BlueRock Therapeuetic: Consultancy; Fate Therapeutics Inc.: Research Funding; Magenta Therapeutics: Consultancy; Childrens' Cancer Research Fund: Research Funding; KidsFirst Fund: Research Funding; Tmunity: Other: Co-founder. Jagasia: Ocugen: Other; Mallinckrodt: Research Funding; Janssen: Research Funding.

Introduction: Autologous stem cell transplants (ASCT) are standard of care for patients with primary refractory or recurrent Hodgkin lymphoma (HL). While transplant results in cure for some patients, others relapse and succumb from their disease. Studies have found high expression of programmed death ligand 1 (PD-L1) in HL cells. The anti-PD-1 monoclonal antibody, nivolumab, has been safe and efficacious in the treatment of relapsed, refractory HL (Ansell et al. 2015). We evaluated the safety and efficacy of nivolumab maintenance therapy post-ASCT in high risk for relapse Hodgkin disease. Methods: Patients with HL with high risk of residual disease following ASCT ( high risk defined as refractory disease, relapse Results: To date, 37 patients were enrolled; median age 36 years; 25 patients (68%) male. The median number of prior systemic regimens was 2 (range 2-4). 25 patients (68%) had relapsed disease, and 12 patients (32%) had primary refractory disease. 18 patients (49%) had extranodal disease at relapse, 6 patients (16%) had B-symptoms at relapse, and 11 patients (30%) had residual disease after salvage, including 10 patients (27%) of whom had 2-3 prior salvage therapies. 22 patients (60%) had received prior brentuximab, and 3 patients (8%) had received prior nivolumab or pembrolizumab. 36 patients received ASCT and 1 patient received tandem ASCT. At the time of data cutoff, 28 patients (76%) had discontinued nivolumab treatment, 22 patients (60%) because they had completed the 6-month treatment course, 4 patients (11%) due to an adverse event (AE) (1 patient each with pain, pneumonitis, rhabdomyolysis, or hypothyroidism), and 2 patients (5%) due to disease progression. The median duration of treatment was 22.1 weeks. 17 patients (46%) experienced a treatment-related AE (TRAE), of which 5 patients (14%) experienced a ≥Grade 3 TRAE. The most common (≥5%) TRAEs were diarrhea, fatigue, bone pain, neutrophil count decreased, pruritus, rash, and vomiting. 2 patients experienced a treatment-related serious AE (pneumonitis, rhabdomyolysis). There were no treatment-related deaths. With a median follow up of 9.2 months, the median PFS and overall survival (OS) have not been reached. The 6 month PFS is 92.1% and the 12-month OS is 100%. There were no differences in OS when stratified based on prior treatment. Conclusions: The use of nivolumab maintenance early after ASCT is safe and tolerable in this high risk patient population. Early efficacy data is promising, but data need to mature to determine the 12 month PFS. Figure 1 Figure 1. Disclosures Bachier: CRISPR: Membership on an entity's Board of Directors or advisory committees; Autolus: Membership on an entity's Board of Directors or advisory committees; Nkarta: Membership on an entity's Board of Directors or advisory committees; Mana: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees. Shah: Umoja: Consultancy; Incyte: Consultancy; Legend: Consultancy; Kite: Consultancy; Miltenyi Biotec: Consultancy, Honoraria, Research Funding; Lily: Consultancy, Honoraria, Research Funding; Epizyme: Consultancy.

8001 Background: CD19 directed CAR T cells are effective in patients with r/r DLBCL, however relapses due to CD19 loss or PDL1 upregulation are common. In this study, we evaluate the safety and efficacy of AUTO3, a CAR T targeting CD19/22 with limited duration of PD-1 blockade. Methods: We constructed a bicistronic retroviral vector encoding both an anti-CD19 (OX40 co-stim) and an anti-CD22 (41BB co-stim) CAR with humanized binders. The cell product was manufactured in a semi-automated and closed process using CliniMACS Prodigy. Patients (≥ 18 years) with r/r DLBCL (NOS) or transformed (tDLBCL); ECOG 6 cells with pem regimen A and B have been completed without DLTs. G > 3 treatment emergent AEs that occurred > 15% were neutropenia (89%), thrombocytopenia (58%), anemia (47%), febrile neutropenia (16%), and hypophosphataemia (16%). Across all dose levels, there were 0% sCRS with primary infusion and 5% severe neurotoxicity (sNT) (1/19), which resolved. There were no cases of sCRS and no neurotoxicity of any grade at > 50 x 106 cells. Eighteen patients were evaluable for efficacy. Among the 11 treated at dose > 50 x 106, the ORR and CRR were 64% and 55%, and all CRs are ongoing (1-12 mth). Two out of 3 patients achieved CR at 450 x 106 cells on pem regimen B. Additional patients and longer follow up, as well as biomarkers, will be presented. Conclusions: AUTO3 at > 50 x 106 CAR T cells with pembrolizumab induces CRs without severe CRS or neurotoxicities of any grade. Clinical trial information: NCT03287817 .

Introduction cGVHD is characterized by an imbalance between effector and regulatory arms of the immune system that results in over production of IL-17 and IL-21. A reduction in the regulatory T (Treg) cells limits the ability of the immune system to re-calibrate this pro-inflammatory environment. KD025 is an oral Rho kinase 2 (ROCK2) selective inhibitor. In vitro data demonstrate KD025 modulates immune homeostasis by shifting the Th17/Treg balance towards Treg. Methods 3 cohorts (C1: 200 mg QD, C2: 200 mg BID, and C3: 400 mg QD) of patients (pts) with cGVHD after 1-3 prior lines of systemic therapy were treated in 28-Day cycles until disease progression. The primary endpoint is overall response rate (ORR) (partial/complete response) per 2014 NIH criteria. Additional endpoints include duration of response (DOR), corticosteroid (CS) dose reductions, Lee Symptom Scale (LSS) score and PD. Blood samples were collected at Cycle 1 Day 1 (C1D1), C2D1, C4D1 and C6D25, and shipped at ambient temperature. PBMC were isolated and kept frozen until analysis. Intracellular expression of IL-17A and FOXP3 was determined by flow cytometry. Results Data as of 6-June-2018 for C1 and C2 are included; C3 data will be available 4Q18. 17 and 16 pts were enrolled in C1 and C2 with median age 52 years, time from cGVHD diagnosis to KD025 treatment of 19 months, and 3 prior regimens. Median duration of treatment was37 (C1) and 33 (C2) weeks. KD025 demonstrated ORR of 65% in C1 and 63% in C2. Responses were rapid (76% at first assessment at 8 weeks) and durable (≥20 weeks) in 82% (C1) and 50% (C2) of responders. Median CS dose was reduced 44% (C1) and 26% (C2). 76% and 56% of pts achieved CS dose reductions. 5/33 (15%) pts discontinued CS. 65% (C1) and 50% (C2) achieved a meaningful improvement (≥7 point reduction) in the LSS score. Common AEs were increased LFTs 42%, URI 33%, anemia 27%, nausea 24%, diarrhea 24% and fatigue 21%. Grade 3+ LFT increases were reported for 6 (18%) pts. 2 pts discontinued treatment due to AEs possibly related to KD025 (headache, diarrhea). SAEs were reported for 11/33 pts, none considered related to KD025. There was no apparent increased risk of infection. Exploratory PD analyses revealed an early increase in the percentage of CD4+ Treg cells by C2D1 with a simultaneous decrease in Th17 cells. The percentage of CD4+ Tregs continued to increase, and the Th17 cells continued to decrease through C6D25. Conclusion KD025 achieved responses with little toxicity. Responses are clinically meaningful with durability, reductions in CS doses and improvement in LSS score. PD data indicate KD025 may restore the Th17/Treg balance.

Introduction: cGVHD exhibits both autoimmune and fibrotic features across multiple organ systems. KD025 is an orally available Rho-associated coiled-coil kinase 2 (ROCK2) selective inhibitor that (1) decreases human T cell IL-21 and IL-17 secretion via STAT3, IRF4 and RORγt regulation; (2) increases percentages and function of Foxp3+ T regulatory cells via a STAT5-dependent mechanism; and (3) reverses established cGVHD in 2 distinct preclinical models. KD025 modulates the immune system by shifting the Th17/Treg balance towards homeostasis. Methods: KD025-208 enrolled 3 sequential cohorts (C) (C1: 200 mg QD, C2: 200 mg BID and C3: 400 mg QD) of patients (pts) with cGVHD after 1-3 prior lines of systemic therapy. Treatment is in 28-Day continuous cycles until disease progression or unacceptable toxicity. The primary endpoint is the overall response rate (ORR) as per 2014 NIH response criteria in the mITT population. Additional endpoints include duration of response (DOR), corticosteroid (CS) dose reductions, failure free survival (FFS) and Lee Symptom Scale (LSS) score. Results: 17, 16 and 21 pts were enrolled in C1, C2, and C3 between Sep-2016 and Mar-2018. Data as of 8-Mar-2019 are included, reflecting a median duration of follow up of 112, 97 and 64 weeks (wks), respectively. At enrollment, median age was 52 yrs, median time from cGVHD diagnosis to treatment was 20 mos, and patients had received a median of 2 prior lines of therapy. 71% of patients were refractory to the last line of therapy prior to enrollment. 50% of pts had cGVHD in ≥4 organs. The median duration of treatment was 37, 33 and 39 wks, respectively. As of 30-Jun-2019, 24% of pts had received >18 months of KD025 therapy. 14 pts remain on KD025 treatment. Reasons for discontinuation included cGVHD progression (18), pt voluntary withdrawal (7), relapse of underlying disease (5), investigator decision (5), AE (3) and death (2). ORR (95% CI) was 65% (38%, 85%) in C1, 69% (41%, 89%) in C2, and 62% (38%, 82%) in C3, i.e. 65% (51%, 77%) across all 3 cohorts. Responses were achieved across key subgroups with ORRs of 62% (24/39) in pts with ≥2 prior lines of systemic therapy, 70% (19/27) in pts with ≥4 organs involved and 60% (25/42) in pts with severe cGVHD. CRs were observed in all affected organs except lung; PRs were observed in lung. Responses were rapid, and often achieved within 8 wks, although 4/35 responses occurred after 24 wks. Of note, organs with fibrotic manifestations such as lungs, joints and eyes responded after 24 weeks in some pts. Responses were durable, with a Kaplan-Meier (K-M) median DOR of 34 weeks across all cohorts. 57% of responders sustained a response for ≥20 wks. The K-M median DOR was 34 wks in pts with ≥2 prior lines of systemic therapy. FFS at 6, 12, 18 and 24 mos was 76%, 47%, 40% and 33%, respectively. Baseline median CS dose was 0.21 mg/kg/day of prednisone equivalent. During treatment with KD025, the median CS dose was reduced by 50%. 67% of pts reduced CS dose and 20% discontinued CS completely. The median CS dose reduction was 66% in responders and 25% in non-responders. 52% of pts reported a clinically meaningful improvement (≥7-point reduction) in LSS score during treatment with KD025 with a median time to improvement of 9 wks and a duration for responders of 21 wks. 63% of responders and 32% of non-responders reported a meaningful improvement in LSS score. KD025 was well tolerated with a median Relative Dose Intensity of 98%. Dose reductions/interruptions occurred in 21/54 pts; median duration of interruption was 8.5 days (range 3-20). AEs were consistent with those expected in cGVHD pts receiving CS. Common AEs were URI (35%), diarrhea (31%), nausea (31%), fatigue (30%), dyspnea (28%), increased LFTs (24%), and peripheral edema (22%). 63% had a Grade ≥3 AE; the most common was dyspnea (13%). Conclusions: Durable and clinically meaningful responses have been observed across all 3 cohorts. KD025 was well tolerated, allowing pts to remain on treatment and realize potential benefits of sustained therapy. Disclosures Jagasia: Kadmon: Consultancy; Incyte: Consultancy; Janssen: Research Funding. Salhotra:Celgene: Other: Research Support; Kadmon Corporation: Other: Non paid consultant. Bachier:Viracyte: Consultancy; Sanofi: Speakers Bureau; Kadmon Corporation, LLC: Consultancy. Lazaryan:Kadmon: Consultancy. Weisdorf:Pharmacyclics: Consultancy; Fate Therapeutics: Consultancy; Incyte: Research Funding. Green:Kadmon Corporation, LLC: Employment. Schueller:Kadmon Corporation LLC: Employment. Huang:Kadmon Corporation, LLC: Employment. Yang:Kadmon Corporation: Employment. Eiznhamer:Kadmon Corporation: Employment. Aggarwal:Kadmon Corporation, LLC: Employment, Equity Ownership. Blazar:Fate Therapeutics, Inc.: Research Funding; Magenta Therapeutics and BlueRock Therapeuetics: Membership on an entity's Board of Directors or advisory committees; Kamon Pharmaceuticals, Inc: Membership on an entity's Board of Directors or advisory committees; Five Prime Therapeutics Inc: Co-Founder, Membership on an entity's Board of Directors or advisory committees; Regeneron Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; RXi Pharmaceuticals: Research Funding; Alpine Immune Sciences, Inc.: Research Funding; Abbvie Inc: Research Funding; Leukemia and Lymphoma Society: Research Funding; Childrens' Cancer Research Fund: Research Funding; KidsFirst Fund: Research Funding; Tmunity: Other: Co-Founder; BlueRock Therapeutics: Membership on an entity's Board of Directors or advisory committees. Lee:Incyte: Research Funding; Syndax: Research Funding; Amgen: Research Funding; Novartis: Research Funding; Takeda: Research Funding; Kadmon: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; AstraZeneca: Research Funding.

Introduction: cGVHD remains a leading cause of post-transplant morbidity / mortality, exhibiting features of both autoimmune and fibrotic diseases across multiple organ systems. cGVHD is characterized by an imbalance between effector and regulatory arms of the immune system that results in over production of inflammatory cytokines including IL-17 and IL-21. Moreover, a persistent reduction in the number of regulatory T (Treg) cells limits the ability of the immune system to re-calibrate this pro-inflammatory environment. KD025 is an orally available Rho-associated coiled-coil kinase 2 (ROCK2) selective inhibitor. In vitro data have demonstrated that KD025 (1) attenuates IL-21 and IL-17 secretion in human CD4+ T cells via STAT3, IRF4 and RORγt regulation, and (2) leads to increased percentages of Foxp3+ CD4+ T cells via a STAT5-dependent mechanism and upregulates the suppressive function of human Tregs. These MOA suggest that KD025 modulates immune homeostasis by shifting the Th17/Treg balance towards a Treg phenotype. No studies have examined KD025 effects in patients with dysregulation associated with high Th17 and low Tregs. Methods: KD025-208 enrolled 3 cohorts (C1: 200 mg QD, C2: 200 mg BID, and C3: 400 mg QD) of patients (pts) with cGVHD after 1-3 prior lines of systemic therapy. Treatment is in 28-Day cycles until disease progression or unacceptable toxicity. The primary endpoint is the overall response rate (ORR) (% pts achieving partial response (PR) or complete response (CR)) as per 2014 NIH response criteria. Secondary endpoints include duration of response (DOR) and corticosteroid (CS) dose reductions. Exploratory endpoints include Lee Symptom Scale (LSS) score and pharmacodynamics (PD). Peripheral blood samples were collected from all pts at Cycle 1 Day 1 (C1D1), C2D1, C4D1 and C6D25, and shipped at ambient temperature. PBMC were isolated and kept frozen until analysis. The intracellular expression of IL-17A and FOXP3 on viable CD3+ CD4+ cells was determined by using multicolor flow cytometry. Results: Data as of 6-June-2018 for C1 and C2 are included; C3 data will be available 4Q18. 17 and 16 pts were enrolled in C1 and C2 with median age 52 years, median time from cGVHD diagnosis to KD025 treatment of 19 months, and a median of 3 prior treatment regimens. Median duration of treatment was 37 (C1) and 33 (C2) weeks (wks). KD025 demonstrated an ORR of 65% in C1 and 63% in C2. ORR in key subgroups is shown below. Responses were rapid (76% achieved at first assessment at 8 wks) and durable with 82% (C1) and 50% (C2) of responders sustaining response for ≥20 wks. Responses including CRs were observed across all affected organ systems except lung (mouth, eyes, joints/ fascia, skin, upper GI, lower GI, esophagus, liver). A previously reported lung PR was deemed on review to be IPF with no cGVHD involvement. During treatment with KD025, median CS dose was reduced by 44% (C1) and 26% (C2). 76% and 56% of pts achieved CS dose reductions. 5/33 (15%) pts discontinued CS. 65% (C1) and 50% (C2) achieved a meaningful improvement (≥7 point reduction) in the LSS score, including both responders (67%) and non-responders (42%). KD025 has been well tolerated. AEs reported were generally consistent with those expected in pts with advanced cGVHD treated with CS. Common AEs were increased LFTs (42%), URI (33%), anemia (27%), nausea (24%), diarrhea (24%) and fatigue (21%). Increased LFTs did not lead to treatment discontinuation, commonly occurred prior to KD025 dosing and were often considered attributable to cGVHD. Grade 3+ LFT increases were reported for 6 (18%) pts. 2 pts discontinued treatment due to AEs possibly related to KD025 (headache, diarrhea). SAEs were reported for 11/33 (33%) pts, none considered related to KD025 treatment. There was no apparent increased risk of infection. Exploratory PD analyses of PBMCs across C1 and C2 revealed an early increase in the percentage of CD4+ Treg cells by C2D1 of KD025 treatment with a simultaneous decrease in Th17 cells. The percentage of CD4+ Tregs continued to increase, and the Th17 cells continued to decrease through C4D1 and C6D25. Conclusion: Treatment with KD025 has demonstrated encouraging clinical responses in cGVHD pts with little toxicity. Responses have been clinically meaningful as evidenced by durability, reductions in CS doses and improvement in LSS score. Exploratory PD data indicate treatment with KD025 may modulate immune homeostasis by restoring the Th17/Treg balance. Figure. Figure. Disclosures Jagasia: Incyte Corporation: Membership on an entity's Board of Directors or advisory committees. Salhotra:Kadmon Corporation, LLC: Consultancy. Bachier:Sanofi: Speakers Bureau; Seattle Genetics: Speakers Bureau. Weisdorf:Seattle Genetics: Consultancy; Pharmacyclics: Consultancy; Equillium: Consultancy; SL Behring: Consultancy; FATE: Consultancy. Green:Kadmon Corporation, LLC: Employment. Schueller:Kadmon Corporation, LLC: Employment. Zanin-Zhorov:Kadmon Corporation, LLC: Employment. Weiss:Kadmon Corporation, LLC: Employment. Eiznhamer:Kadmon Corporation, LLC: Employment. Aggarwal:Kadmon Corporation, LLC: Employment. Blazar:Kadmon Corporation, LLC: Consultancy, Research Funding. Lee:Takeda: Research Funding; Kadmon: Research Funding; Amgen: Consultancy, Research Funding; Mallinckrodt: Honoraria; Incyte: Consultancy; Pfizer: Consultancy; Onyx: Research Funding.

Introduction: Allogeneic stem cell transplantation is an appropriate treatment option in patients (pts) with high-risk multiple myeloma (MM), but carries a mortality risk as a consequence of graft-versus-host disease (GVHD) and relapsed disease. Proteasome inhibitors have been shown to stimulate allogeneic immune cells to eliminate myeloma cells and at the same time reduce the incidence and severity of GVHD. The use of proteasome inhibitors after stem cell transplant can therefore prolong remissions after transplant and reduce the incidence of GVHD. Ixazomib is an orally bioavailable, reversible inhibitor of the 20S proteasome that has also shown impressive anti-myeloma activity in both the relapsed/refractory and the upfront setting. This is a Phase II, open-label, multicenter, non-randomized study to determine the feasibility of Ixazomib as maintenance after allogeneic stem cell transplant for MM. Here we present results from pts in the three treatment cohorts. Methods: High risk pts (including chromosome 17p, partial deletion (del(17p), t(4;14), t(14;16), t(14;20), plasma cell leukemia, or progression-free survival of less than 2 years after autologous stem cell transplant) who received an allogenic stem cell transplant and had no evidence of >Grade 2 GVHD or any GVHD requiring methylprednisolone were eligible to enroll between Days 45 and 120 after transplant. Pts received a weekly oral ixazomib dose on Days 1, 8, and 15 of each 28-day cycle for 6 cycles. Pts were treated at 2.3 mg (Cohort 1), 3 mg (Cohort 2), and 4 mg (Cohort 3). Results: To date, 7 pts were enrolled (3 on Cohort 1, 3 on Cohort 2, and 1 on Cohort 3); median age 49 years; 5 pts (71%) female; 4 pts (57%); International Staging System Grade ≥ 2. The median number of prior systemic regimens was 4 (range 3-8). 100% of pts had received autologous stem cell transplant. Median number of prior autologous transplants was 2 (range 1-3). Conditioning regimen prior to allogeneic stem cell transplant included fludarabine + melphalan (n = 6) and fludarabine + total body irradiation (n = 1). All pts received peripheral blood stem cells, donors included matched related donors (n=2) and unrelated donors (n=5). The median number of weeks of treatment were Cohort 1, 24 wks; Cohort 2, 16 wks; Cohort 3, 6 wks. To date, there have been no dose-limiting toxicities, 1 dose interruption on Cohort 1 due to thrombocytopenia, and 1 dose reduction on Cohort 2 due to rash. 5 pts (71%) have discontinued treatment, 3 pts (43%) due to disease progression and 2 pts (29%) have completed treatment. 2 pts (29%) were still on active treatment at the time of data cut-off. 3 pts (43%) have died due to disease progression. The median time on study overall was 9 months (range 2-28 months). Of the 6 pts (86%) eligible for response analysis, 2 pts (33%) had a stringent complete response, 1 pt (17%) had a complete response, 2 pts (33%) had a very good partial response, and 1 pt (17%) had progressive disease as a best overall response. The most common ≥ Grade 3 adverse events (AEs) were thrombocytopenia (3 pts, 43%) and hypertension (2 pts, 29%). 3 pts (43%) had ≥ Grade 3 treatment-related AEs of thrombocytopenia (3 pts, 43%) and rash (1 pts, 14%). 1 pt (14%) had treatment-related serious adverse events (vomiting and fever). Acute GVHD was reported for 5 pts (maximum Grade 1), chronic GVHD occurred in 4 pts (limited: 2 pts, extensive: 2 pts). Conclusions: There have been no dose-limiting toxicities on these 3 cohorts. The maximum-tolerated dose has not been reached for this study and enrollment is continuing. Initial response data is promising. Disclosures Matous: Celgene: Speakers Bureau; Multiple Myeloma Advisory Committee: Membership on an entity's Board of Directors or advisory committees. Berdeja: Vivolux: Research Funding; Constellation: Research Funding; Takeda: Research Funding; Curis: Research Funding; Teva: Research Funding; Novartis: Research Funding; Janssen: Research Funding; Celgene: Research Funding; BMS: Research Funding; Bluebird: Research Funding; Amgen: Research Funding; Abbvie: Research Funding.