itacitinib (INCB039110) / Incyte, Innovent Biologics - LARVOL DELTA

Outcomes with itacitinib prophylaxis for cytokine release syndrome: A systematic review (ASH 2025) - "Patients were planned to receive axicabtagene ciloleucel for relapsed/refractory large B-cell lymphoma (rrLBCL). Itacitinib prophylaxis may prevent high-grade CRS and other immune-mediated adverse events such as ICANS and GVHD without reducing the treatment responses. Future high-quality trials with larger patient populations are required to validate these findings further."

Cytokine release syndrome • Review • Acute Graft versus Host Disease • Acute Myelogenous Leukemia • B Cell Lymphoma • Graft versus Host Disease • Hematological Malignancies • Immunology • Inflammation • Large B Cell Lymphoma • Leukemia • Lymphoma • Myelodysplastic Syndrome • Non-Hodgkin’s Lymphoma

An open-label phase I study of JAK inhibitor ruxolitinib with and without CTLA-4 ig abatacept for the prophylaxis of graft-versus-host ddsease and cytokine release syndrome after T-cell replete haploidentical peripheral blood hematopoietic cell transplantation (ASH 2025) - P1 | "We previouslydemonstrated that JAK1 inhibition with itacitinib is effective in preventing aGVHD and CRS, with excellentlong term GRFS and OS in a high-risk population undergoing allo-HCT...If safe, we will expand this approach to combine ruxolitinib and abatacept andreduce exposure to traditional immunosuppressants mycophenolate mofetil (MMF) and tacrolimus...All patients received standarddose post-transplant cyclophosphamide... Ruxolitinib with PB haplo-HCT appears safe, with no engraftment failure and promptengraftment. Severe CRS has not been seen in this trial. Rates of acute and chronic GVHD are low, and nopatients have relapsed during short follow-up to date."

Clinical • Cytokine release syndrome • P1 data • Acute Graft versus Host Disease • Chronic Graft versus Host Disease • CNS Disorders • Graft versus Host Disease • Immunology • Infectious Disease • Inflammation • Influenza • Pneumonia • Respiratory Diseases • Transplantation • CTLA4

Itacitinib in combination with post-transplant cyclophosphamide and tacrolimus (ICT) as GVHD prophylaxis for reduced intensity matched donor peripheral blood stem cell hematopoietic cell transplantation: Interim analysis (ASH 2025) - P2 | "We conducted a single-center pilot study (NCT05364762) to evaluate the safety ofadding itacitinib to PTCy-based prophylaxis with tacrolimus, schedule for 60 or 90 days, in patientsundergoing matched (related or unrelated) donor peripheral blood stem cell (PBSC) HCT usingfludarabine (25 mg/m2: days -7 to -3) and melphalan (100 mg/m2: day -2) as conditioning.GvHD prophylaxis consisted of PTCy (50 mg/kg: days +3 and +4), itacitinib (200 mg, oral, daily from day +5to +100), and tacrolimus beginning on day +6. The 1-year GVHD-freeand relapse-free survival (GRFS) was 79% (95% CI: 53–92).The addition of itacitinib to PTCy and tacrolimus-based GVHD prophylaxis (ICT) was safe and well-tolerated, with low incidence of acute and chronic GVHD, no NRM, and promising 1-year GRFS andsurvival outcomes. These results support further study of JAK1 inhibition in combination with PTCyplatform for GVHD prophylaxis regimens to optimize immune tolerance post-HCT."

Combination therapy • Post-transplantation • Acute Graft versus Host Disease • Acute Kidney Injury • Chronic Graft versus Host Disease • Chronic Myelomonocytic Leukemia • Febrile Neutropenia • Graft versus Host Disease • Hematological Disorders • Immunology • Infectious Disease • Inflammation • Nephrology • Neutropenia • Septic Shock • Thrombocytopenia • Transplantation

HLH-JAK, the first OPEN-label, phase II study evaluating ANTI-JAK1 itacitinib, for NON severe HLH in adults. (ASH 2025) - P2 | "Cytokines involved in HLHsyndrome activate the JAK/STAT pathway in immune cells, particularly gamma- interferon through JAK1.Kinase inhibitors blocking JAK activity, particularly Ruxolitinib a JAK1/2 inhibitor, have shown someefficacy in murine genetic models of HLH...In the absence of organ failure,fibrinogen<0.5 g/L, platelets<20 G/l, the need for ICU transfer, or etoposide treatment, HLH patients wereconsidered non-severe... Itacitinib, anti-JAK1 inhibitor, demonstrated encouraging efficacy in adult patients with non-severe HLH, with a response rate at Day 15 well above the prespecified efficacy threshold, and theminimum required number of responses was met despite the premature termination of the trial. Thetreatment was well tolerated, with no grade ≥3 adverse events related to itacitinib. These promisingpreliminary results warrant further comparative studies to confirm the efficacy and safety of anti-JAKinhibitor in this setting."

Clinical • P2 data • B Cell Non-Hodgkin Lymphoma • Hematological Malignancies • Hemophagocytic lymphohistiocytosis • Immunology • Lymphoma • Non-Hodgkin’s Lymphoma • Rare Diseases • IFNG • JAK1

Janus Kinase Inhibitors During Pregnancy and Adverse Drug Reactions: A Pharmacovigilance Disproportionality Analysis in VigiBase. (PubMed, Clin Transl Sci) - "This study analyzed VigiBase, the World Health Organization global pharmacovigilance database of individual case safety reports (ICSRs), to assess signals of disproportionate reporting (SDRs) for pregnancy-related adverse drug reactions (ADRs) reported with systemic JAKIs, including abrocitinib, baricitinib, deucravacitinib, fedratinib, filgotinib, itacitinib, momelotinib, pacritinib, peficitinib, ritlecitinib, ruxolitinib, tofacitinib, and upadacitinib. Findings should be interpreted cautiously given the limitations of spontaneous reporting systems and the exploratory nature of the analysis. Further studies are needed to better characterize the JAKI safety in pregnancy."

Adverse drug reaction • Adverse events • Journal • Immunology • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology

Itacitinib Pre-modulation in DLBCL Receiving CAR T Cell Therapy (clinicaltrials.gov) - P2 | N=27 | Recruiting | Sponsor: H. Lee Moffitt Cancer Center and Research Institute | Trial completion date: Oct 2026 ➔ Jan 2027 | Trial primary completion date: Oct 2025 ➔ Jan 2026

Trial completion date • Trial primary completion date • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CRP • JAK1

T-prolymphocytic leukemia(T-PLL) – What are recent improvements? (DGHO 2025) - "With the aim to further improve clinical outcomes, a prospective phase-II trial was conducted by the German CLL Study group using an induction therapy with fludarabine, cyclophosphamide and mitoxantrone (FMC) followed by alemtuzumab consolidation therapy...CIBMTR Data of 266 patients with T-PLL demonstrated a 4-year disease-free survival (DFS) of 25.7% and OS of 30.0%.There are recent clinical pilot data derived from drug screening efforts that provide valuable insights: venetoclax, HDAC-inhibition plus idasanutlin (MDM2 antagonist, activation of p53), and drugs targeting autophagy (thapsigargin and bafilomycin A1), nuclear export (selinexor) or inhibitor of apoptosis proteins (IAPs; birinapant). Valuable trial data teach us on the limited applicability of pre-clinical results, i.e. the limited efficacy of venetoclax+ibrutinib or of itacitinib + alemtuzumab.Overall, responses after induction therapy remain dissatisfactory as most patients relapse even after a CR..."

Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Prolymphocytic Leukemia

A Micro-Engineered Heart Tissue Model of Desmin-related Cardiomyopathy Caused by Mutant αB Crystalin. (PubMed, bioRxiv) - "JAK1 inhibition with Itacitinib partially restored contractile function at higher pacing frequencies, suggesting JAK1 inhibition as a viable therapeutic strategy. By preserving human-specific structural and functional features, our µHT platform enables mechanistic characterization of proteotoxic cardiomyopathies and offers a scalable system for targeted drug screening."

Journal • Cardiomyopathy • Cardiovascular • CRYAB • JAK1

HLH-JAK, the First Open-Label, Phase II Study Evaluating Anti-JAK1 Itacitinib, for Non Severe HLH in Adults (ASH 2023) - P2 | "Kinase inhibitors blocking JAK activity, particularly Ruxolitinib a JAK1/2 inhibitor, have shown some efficacy in murine genetic models of HLH...In the absence of organ failure, fibrinogen<0.5 g/L, platelets<20 G/l, the need for ICU transfer, or etoposide treatment, HLH patients were considered non-severe... As first line treatment, itacitinib monotherapy provided encouraging clinical activity characterized by a high RR and durable response and no safety issues were notified. The second stage of HLH JAK is ongoing. Clinical trial information: NCT NCT05063110"

Clinical • P2 data • B Cell Non-Hodgkin Lymphoma • Hematological Disorders • Hematological Malignancies • Hemophagocytic lymphohistiocytosis • Immunology • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Rare Diseases • IFNG • JAK1

Hemophagocytic Syndrome Associated with CAR-T Cell Therapy (ASH 2024) - "on the use of drugs for cell therapy-related HLH at EBMT centers, common clinical combinations include corticosteroids + chemotherapy, corticosteroids + monoclonal antibodies + chemotherapy, corticosteroids + chemotherapy + cytokine blockade, corticosteroids + cytokine blockade, and corticosteroids alone. We introduce commonly used specific medications, including etoposide, emapalumab, the IL-six monoclonal antibody siltuximab, the anti-interleukin (IL)-six receptor monoclonal antibody tocilizumab, the interleukin-1 receptor antagonist anakinra, and JAK-one and JAK-two blockers such as ruxolitinib and the JAK-one inhibitor itacitinib, among others."

CAR T-Cell Therapy • IO biomarker • Hematological Disorders • Hematological Malignancies • Hemophagocytic lymphohistiocytosis • Hypertriglyceridemia • Immunology • Infectious Disease • Oncology • Rare Diseases • Rheumatology • Solid Tumor • Thrombocytopenia • IFNG

Itacitinib for Prevention of Graft-Versus-Host Disease and Cytokine Release Syndrome with T-Cell Replete Peripheral Blood Haploidentical Transplantation (ASH 2023) - P1 | "GVHD prophylaxis was tacrolimus, mycophenolate mofetil, and post-transplant cyclophosphamide. Itacitinib with PB haplo-HCT was safe with low rates of acute and chronic GVHD, without increased risk of relapse or transplant related mortality. Severe CRS was not seen in this trial, and no anti-IL6 or steroid therapy was used. The addition of Jak inhibition to standard PtCy based GVHD prophylaxis was associated with encouraging rates of GRFS and OS on this pilot and expansion study."

Cytokine release syndrome • IO biomarker • Acute Graft versus Host Disease • Chronic Graft versus Host Disease • Graft versus Host Disease • Immunology • Inflammation • Transplantation • CD4 • CD8 • CD80 • CD86 • IFNG • JAK1 • LAG3 • PD-1 • TIGIT

Janus Kinase (JAK) 1 Inhibition Results in Significant Changes in Serum Proteins and Peripheral T-Cell Populations That Correlated with Clinical Scores in Chronic Graft Versus Host Disease (GVHD) Patients (an Analysis from GRAVITAS-309) (ASH 2023) - P2/3 | "The dose-finding, open-label, randomized portion of the study initially investigated itacitinib at 200 mg once daily (qd) and 300 mg qd in combination with CS (methylprednisolone or prednisone); both doses were well tolerated. Analysis of patient samples from GRAVITAS-309 revealed that serum elafin and DKK3 levels significantly correlated with skin GVHD scores, possibly reflecting the systemic origin of observed skin manifestations. Serum levels of osteopontin, CXCL9, and CXCL10 were specifically reduced by itacitinib in patients with cGVHD and may represent potential pharmacodynamic markers. Observed changes in different peripheral T-cell populations in patients' samples following itacitinib treatment were consistent with those reported in murine GVHD models, suggesting a potential role of naive CD4+ T cells in driving this disease."

Clinical • Acute Graft versus Host Disease • Chronic Graft versus Host Disease • Graft versus Host Disease • Immunology • CCR7 • CD8 • CXCL10 • CXCL9 • DKK3 • SPP1

Preliminary Results from a Phase 1b Dose De-Escalation Stage of Abnl-Marro 001: An International MDS/MPN Working Group Study (ASH 2023) - P1/2 | "The only approved therapies for MDS/MPNs are hydroxyurea, decitabine (oral decitabine/cedazuridine and parenteral decitabine) or azacitidine (parenteral) for pts with CMML. Based on the preliminary results of the phase 1b study, the dosing schedule of 35 mg DEC / 100 mg CED daily for 5 days in combination with itacitinib 300 mg daily for 28 days was selected as the RP2D as it balanced clinical efficacy with an acceptable and manageable safety profile. This regimen and dose are being utilized in a 28-day cycle in the ongoing global, multi-center phase 2 study (NCT04061421)."

P1 data • Chronic Myelomonocytic Leukemia • Constipation • Gastroenterology • Gastrointestinal Disorder • Hematological Disorders • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Myeloproliferative Neoplasm • Neutropenia • Oncology • Thrombocytopenia

Itacitinib for the Prevention of Immune Effector Cell Therapy–Associated Cytokine Release Syndrome: Results from the Phase 2 Incb 39110-211 Placebo-Controlled Randomized Cohort (ASH 2023) - P2 | "Protocol did not allow tocilizumab for treatment of grade 1 CRS unless CRS did not improve after 72 hours of supportive treatment. Results from the randomized, placebo-controlled portion of Study INCB 39110-211 have shown prophylaxis treatment with itacitinib 200 mg bid to be well tolerated and resulted in a lower rate and grade of CRS and ICANS after lymphoma treatment with axicabtagene ciloleucel. Incidence of grade 3/4 neutropenia and thrombocytopenia not resolved at Day 28 was higher with itacitinib vs placebo. Rates of severe infections were comparable in both arms."

Clinical • Cytokine release syndrome • IO biomarker • P2 data • B Cell Lymphoma • Follicular Lymphoma • Hematological Disorders • Hematological Malignancies • Hypotension • Infectious Disease • Inflammation • Large B Cell Lymphoma • Lymphoma • Nephrology • Neutropenia • Non-Hodgkin’s Lymphoma • Oncology • Septic Shock • Thrombocytopenia

Evaluation of Itacitinib Impact on TNFα Levels Following Immune Effector Cell (IEC) Therapy Using PKPD Modeling and Simulation Approaches (ASH 2024) - P2 | "Pharmacokinetic (PK) and PD modeling was applied to describe the inhibition of itacitinib on TNFα levels following CAR-T infusion.Objectives : The primary aim of the PKPD modeling analysis was to develop a mechanistic model to evaluate itacitinib anti-inflammatory action on systemic levels of TNFα following CAR-T therapy and itacitinib once-daily (QD) and twice-daily (BID) dosing regimens.Methods : The phase 2 study PKPD-evaluable population included 63 patients receiving CAR-T (axicabtagene ciloleucel) therapy for hematologic malignancies incorporating Part 1 (open-label; itacitinib 200 mg QD) and Part 2 (randomized, double-blind; itacitinib 200 mg BID vs placebo). The simulated BID regimen suppressed TNFα more effectively than QD, based on AUC metrics : 4391 pg∙hours/mL vs 2905 pg∙hours/mL.Conclusions : Aggregated TNFα profiles were adequately described by the integrated PKPD model incorporating CAR-T stimulatory dynamics with linear effect coupled with nonlinear..."

IO biomarker • Hematological Malignancies • Oncology • JAK1 • TNFA

Final Analysis of Phase 2a Study of Adding Itacitinib to Tacrolimus/Sirolimus Gvhd Prophylaxis after Fludarabine/Melphalan-Based Conditioning Hematopoietic Cell Transplantation for Acute Leukemias, Myelodysplastic Syndrome (MDS), or Myelofibrosis (MF) (ASH 2024) - P2 | "Introduction : In a phase 2a clinical trial (NCT04339101), we hypothesized that adding Itacitinib, a potent and selective Janus kinases-1 inhibitor, to the standard tacrolimus/sirolimus (Tac/Siro) graft-vs-host-disease (GVHD) prophylaxis is safe and can potentially improve GVHD-free, relapse-free survival (GRFS). The study met the primary endpoint of 1-year GRFS at 54%, which is compared favorably to Tac/Siro or Tac/methotrexate as GVHD prophylaxis, similar to the results observed in PTCy/tacrolimus/MMF (BMT CTN 1703). The observed aGVHD rate was lower than our previously published historic data in patients receiving Tac/Siro alone (31% vs. 9%), half of the cases with grade 2-4 aGVHD were diagnosed after day +100 when itacitinib administration stopped per protocol therapy, indicating the need for further refinement in tapering strategy of Tac/Siro/itacitinib, potentially guided by the cytokine/cellular biomarkers identified in our study."

P2a data • Acute Graft versus Host Disease • Chronic Graft versus Host Disease • Graft versus Host Disease • Hematological Malignancies • Immunology • Leukemia • Myelodysplastic Syndrome • Myelofibrosis • Oncology • Transplantation • IL10 • IL17A • TNFRSF1A

Itacitinib for the Treatment of Bronchiolitis Obliterans Syndrome After Donor Hematopoietic Cell Transplant (clinicaltrials.gov) - P1 | N=8 | Terminated | Sponsor: M.D. Anderson Cancer Center | Trial completion date: May 2027 ➔ Oct 2025 | Active, not recruiting ➔ Terminated | Trial primary completion date: May 2027 ➔ Oct 2025; <75% participation

Trial completion date • Trial primary completion date • Trial termination • Pulmonary Disease • Respiratory Diseases • Transplantation

Itacitinib for the Prevention of Graft Versus Host Disease (clinicaltrials.gov) - P2 | N=31 | Active, not recruiting | Sponsor: M.D. Anderson Cancer Center | Phase classification: P1 ➔ P2

Phase classification • Graft versus Host Disease • Hematological Disorders • Immunology

Comprehensive genomic profiling to guide personalized targeted and immunotherapy in gastrointestinal tumors: Subgroup analysis of the ROME trial (ESMO-GI 2025) - P2 | "Funding: Erlotinib, Pertuzumab, Vemurafenib, Trastuzumab Emtansine, Alectinib, Vismodegib, Cobimetinib, Atezolizumab, Trastuzumab, Ipatasertib (GDC-0068), Entrectinib and Pralsetinib were provided by Roche; Everolimus, Lapatinib, Alpelisib were provided by Novartis, Palbociclib and Talazoparib were provided by Pfizer, Ipilimumab and Nivolumab were provided by Bristol Myers Squibb (BMS); Brigatinib was provided by Takeda Pharmaceutical Co.; Ponatinib, Itacitinib (INCB039110), Pemigatinib (INCB054828) were provided by Incyte; Selpercatinib was provided by Eli Lilly; Tepotinib was provided by the healthcare business of Merck KGaA, Darmstadt, Germany (CrossRef Funder ID: 10.13039/100009945). CGP with MTB-guided TT may identify patients with GI cancer who benefit from targeted therapies not routinely available in clinical practice. The roles of TMB and potential disease-specific thresholds deserve further investigation."

IO biomarker • Tumor mutational burden • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • HER-2 • PIK3CA • TMB

Itacitinib for the Treatment of Bronchiolitis Obliterans Syndrome After Donor Hematopoietic Cell Transplant (clinicaltrials.gov) - P1 | N=8 | Active, not recruiting | Sponsor: M.D. Anderson Cancer Center | Trial completion date: May 2025 ➔ May 2027 | Trial primary completion date: May 2025 ➔ May 2027

Trial completion date • Trial primary completion date • Pulmonary Disease • Respiratory Diseases • Transplantation

Itacitinib With High-dose Posttransplantation Cyclophosphamide in Older Patients (clinicaltrials.gov) - P1 | N=32 | Active, not recruiting | Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Recruiting ➔ Active, not recruiting

Enrollment closed • Hematological Malignancies • Inflammation • Leukemia • Multiple Myeloma • Myelodysplastic Syndrome • Myeloproliferative Neoplasm • Oncology • Plasma Cell Leukemia • Prolymphocytic Leukemia • Transplantation

New Therapies and Targeted Treatments: MDS/ MPN Overlap Syndromes (SOHO 2025) - "This has led to the use of parenteral azanucleosides — decitabine and azacitidine — and, perhaps most successfully in the United States, the oral agent decitabine/ cedazuridine (Dec-C)...While decitabine led to improved response rates, it failed to show benefit in event-free survival (EFS) or overall survival (OS) over the hydroxyurea arm, 5 raising questions about the role of azanucleosides — at least in MP-CMML — and underscoring the urgent need for disease-specific therapies for patients with MPCMML and other MDS/MPNs...This yielded promising responses, 8 but the arm was closed, as itacitinib was discontinued by the manufacturer...9 Given these findings, in the phase 2 PREACH study in Australia comparing lenzilumab plus azacitidine in untreated, high-risk RAS- mutated CMML, investigators reported a 55% complete response (CR) rate, found to be durable at 18 months...STX-0712 is a cytotoxicity targeting antibody (CyTAC) that links an antibody designed to induce..."

IO biomarker • Acute Myelogenous Leukemia • Chronic Myeloid Leukemia • Chronic Myelomonocytic Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Myeloproliferative Neoplasm • Oncology • ABL1 • BCR • CCL2 • CCR2 • CSF2 • LILRB4 • SF3B1

Targeting synergetic endothelial inflammation by inhibiting NFKB and JAK-STAT pathways. (PubMed, iScience) - "JAK1 inhibitor itacitinib blocked IFNγ-, but not TNFα-induced proteomic responses...Imaging of Von Willebrand Factor (VWF) revealed an extracellular VWF network induced by combined stimulation, a phenotype which was reverted by both inhibitors. This study provides a preliminary basis for inhibiting endothelial inflammation in vascular inflammatory disorders."

Journal • Inflammation • IFNG • TNFA

Itacitinib Pre-modulation in DLBCL Receiving CAR T Cell Therapy (clinicaltrials.gov) - P2 | N=27 | Recruiting | Sponsor: H. Lee Moffitt Cancer Center and Research Institute | Trial completion date: Jun 2026 ➔ Oct 2026 | Trial primary completion date: Jun 2025 ➔ Oct 2025

Trial completion date • Trial primary completion date • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CRP • JAK1

A phase 2 study of itacitinib alone or in combination with low-dose ruxolitinib in patients with myelofibrosis. (PubMed, Leuk Res) - "Overall, 8 of 23 patients enrolled achieved SVR at week 24; larger average changes in SVR at week 12 were observed for itacitinib monotherapy vs. the combination. No unexpected safety signals were observed."

Journal • P2 data • Fatigue • Hematological Disorders • Myelofibrosis • Myeloproliferative Neoplasm • Oncology • Thrombocytopenia • JAK1