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

Experimental JAK inhibitors: the current, present and future in graft-versus-host disease management? (PubMed, Expert Opin Investig Drugs) - "We evaluate the efficacy and safety of selective and nonselective agents, including ruxolitinib, baricitinib, itacitinib, pacritinib, and rovadicitinib. We anticipate a transition from the current 'steroid-first' paradigm to risk-stratified algorithms utilizing biomarker profiling and novel combination strategies. While ruxolitinib is the current cornerstone, the development of highly selective inhibitors and the resolution of financial access barriers will be crucial for establishing JAK inhibitors as the frontline standard of care over the next decade."

Journal • Review • Acute Graft versus Host Disease • Chronic Graft versus Host Disease • Graft versus Host Disease • Immunology • Transplantation

INCIDENCE OF EBV DNAEMIA AND POSTTRANSPLANT LYMPHOPROLIFERATIVE DISORDER (PTLD) AMONG HCT WITH POSTTRANSPLANT CYCLOPHOSPHAMIDE (PTCY). A SINGLE CENTER EXPERIENCE (EBMT 2026) - "Patients received bone marrow or peripheral blood stem cell (PBSC) graft on Day (D) 0; PTCy (50 mg/kg/day) was given on D +3 and +4, and tacrolimus (or sirolimus) plus mycophenolate mofetil (or investigational itacitinib) starting on D +5...Of 18 patients treated with Rituximab, 17 (94.4%) cleared EBV DNAemia and 1 patient died with EBV DNAemia from GVHD... 1) The cumulative incidence of EBV viremia and cs-EBV DNAemia at D +365 among PTCy recipients was 15.8% and 4.3% respectively. 2) Probable PTLD developed in 10 (2.4%) patients. 3) ATG was associated with cs-EBV DNAemia and probable PTLD."

Clinical • Post-transplantation • Graft versus Host Disease • Immunology • Transplantation

PERI-TRANSPLANT RUXOLITINIB FOR GRAFT-VS-HOST-DISEASE (GVHD) PREVENTION IN PEDIATRIC AND YOUNG ADULT PATIENTS UNDERGOING MYELOABLATIVE HEMATOPOIETIC CELL TRANSPLANTATION (HCT): INTERIM ANALYSIS (EBMT 2026) - P2 | "Similarly, our group showed that peri-HCT itacitinib, another JAK 1 inhibitor, is safe when added to tacrolimus/sirolimus as GVHD prophylaxis, with 100% engraftment and low rates of acute/chronic GVHD in adults. We show that peri-HCT ruxolitinib did not interfere with engraftment post-HCT. In addition, our data supports the safety and feasibility of adding ruxolitinib to tacrolimus/methotrexate as GVHD prophylaxis in young patients receiving HCT. Accrual is ongoing."

Clinical • Acute Graft versus Host Disease • Chronic Graft versus Host Disease • Gastroenterology • Gastrointestinal Disorder • Graft versus Host Disease • Immunology • Infectious Disease • Lymphoma • Myelodysplastic Syndrome • Myelofibrosis • Pediatrics • Transplantation

CHARACTERISTICS OF CLINICAL TRIALS IN GRAFT-VERSUS-HOST DISEASE: LANDSCAPE OF STUDY DRUGS AND ASSESSMENT OF OUTCOME MEASURES (EBMT 2026) - "The most frequent treatments studied were corticosteroids (n=64), followed by mesenchymal stem cells (n=52), ruxolitinib (n=31), extracorporeal photopheresis (n=26), fecal microbiota transplantation (n=17), rituximab (n=15), belumosudil and cyclosporin (n=13 each), itacitinib (n=11), axatilimab and donor regulatory T-cells (n=10 each), and ibrutinib (n=9). Acute and chronic GvHD remain major areas of clinical research, with their distinct clinical courses reflected in differences in trial design and outcome measures. Recent shifts toward multicenter designs, shorter study durations, and more frequent evaluation of targeted therapies suggest evolving priorities and growing methodological maturity in GvHD trial planning."

Clinical • Acute Graft versus Host Disease • Bone Marrow Transplantation • Chronic Graft versus Host Disease • Graft versus Host Disease • Immunology

ITACITINIB IN COMBINATION WITH POST-TRANSPLANT CYCLOPHOSPHAMIDE AND TACROLIMUS (ICT) AS GVHD PROPHYLAXIS FOR REDUCED INTENSITY MATCHED DONOR HEMATOPOIETIC CELL TRANSPLANTATION (HCT): FINAL ANALYSIS (EBMT 2026) - P2 | "We conducted a single-center study (NCT05364762) evaluating the safety of adding itacitinib to PTCy-based prophylaxis with tacrolimus, for 60 or 90 days, in patients undergoing matched related or unrelated peripheral blood stem cell (PBSC) HCT following fludarabine (25 mg/m2: days -7 to -3) and melphalan (100 mg/m2: day -2) conditioning. Adding itacitinib to PTCy and tacrolimus-based GVHD prophylaxis (ICT) was safe and well-tolerated, with low GVHD rates, no NRM, and promising 1-year survival. These results support further study of JAK1 inhibition with the PTCy platform to optimize immune tolerance post-HCT."

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

PERI-TRANSPLANT RUXOLITINIB FOR GRAFT-VS-HOST-DISEASE (GVHD) PREVENTION IN PEDIATRIC AND YOUNG ADULT PATIENTS UNDERGOING MYELOABLATIVE HEMATOPOIETIC CELL TRANSPLANTATION (HCT): INTERIM ANALYSIS (EBMT 2026) - P2 | "Similarly, our group showed that peri-HCT itacitinib, another JAK 1 inhibitor, is safe when added to tacrolimus/sirolimus as GVHD prophylaxis, with 100% engraftment and low rates of acute/chronic GVHD in adults. We show that peri-HCT ruxolitinib did not interfere with engraftment post-HCT. In addition, our data supports the safety and feasibility of adding ruxolitinib to tacrolimus/methotrexate as GVHD prophylaxis in young patients receiving HCT. Accrual is ongoing."

Clinical • Acute Graft versus Host Disease • Chronic Graft versus Host Disease • Gastroenterology • Gastrointestinal Disorder • Graft versus Host Disease • Immunology • Infectious Disease • Lymphoma • Myelodysplastic Syndrome • Myelofibrosis • Pediatrics • Transplantation

INCIDENCE OF EBV DNAEMIA AND POSTTRANSPLANT LYMPHOPROLIFERATIVE DISORDER (PTLD) AMONG HCT WITH POSTTRANSPLANT CYCLOPHOSPHAMIDE (PTCY). A SINGLE CENTER EXPERIENCE (EBMT 2026) - "Patients received bone marrow or peripheral blood stem cell (PBSC) graft on Day (D) 0; PTCy (50 mg/kg/day) was given on D +3 and +4, and tacrolimus (or sirolimus) plus mycophenolate mofetil (or investigational itacitinib) starting on D +5...Of 18 patients treated with Rituximab, 17 (94.4%) cleared EBV DNAemia and 1 patient died with EBV DNAemia from GVHD... 1) The cumulative incidence of EBV viremia and cs-EBV DNAemia at D +365 among PTCy recipients was 15.8% and 4.3% respectively. 2) Probable PTLD developed in 10 (2.4%) patients. 3) ATG was associated with cs-EBV DNAemia and probable PTLD."

Clinical • Post-transplantation • Graft versus Host Disease • Immunology • Transplantation

CHARACTERISTICS OF CLINICAL TRIALS IN GRAFT-VERSUS-HOST DISEASE: LANDSCAPE OF STUDY DRUGS AND ASSESSMENT OF OUTCOME MEASURES (EBMT 2026) - "The most frequent treatments studied were corticosteroids (n=64), followed by mesenchymal stem cells (n=52), ruxolitinib (n=31), extracorporeal photopheresis (n=26), fecal microbiota transplantation (n=17), rituximab (n=15), belumosudil and cyclosporin (n=13 each), itacitinib (n=11), axatilimab and donor regulatory T-cells (n=10 each), and ibrutinib (n=9). Acute and chronic GvHD remain major areas of clinical research, with their distinct clinical courses reflected in differences in trial design and outcome measures. Recent shifts toward multicenter designs, shorter study durations, and more frequent evaluation of targeted therapies suggest evolving priorities and growing methodological maturity in GvHD trial planning."

Clinical • Acute Graft versus Host Disease • Bone Marrow Transplantation • Chronic Graft versus Host Disease • Graft versus Host Disease • Immunology

Phase 1B pilot study of itacitinib with alemtuzumab in patients with T-cell prolymphocytic leukemia. (PubMed, Blood Neoplasia) - P1 | "Continued studies evaluating JAK inhibitors in patients with T-PLL are warranted. This trial was registered at www.clinicaltrials.gov as #NCT03989466."

Clinical • Journal • P1 data • Hematological Malignancies • Leukemia • Oncology • Prolymphocytic Leukemia • Transplantation • IL2RG • JAK3 • STAT5B • TCL1A

Active Myeloid Target Compound Combinations in MDS/MPN Overlap Syndromes Overlap Syndromes (ABNL-MARRO) (clinicaltrials.gov) - P1/2 | N=94 | Recruiting | Sponsor: Michael Savona | Trial completion date: Aug 2025 ➔ Dec 2027 | Trial primary completion date: Aug 2024 ➔ Aug 2027

Trial completion date • Trial primary completion date • Myelodysplastic Syndrome

Itacitinib for the Prevention of IEC Therapy-Associated CRS: Results From the Two-Part Phase 2 INCB 39110-211 Study. (PubMed, Blood) - P2 | "Patients in part 1 received once-daily itacitinib 200 mg 3 days before IEC therapy (axicabtagene ciloleucel [axi-cel], brexucabtagene autoleucel, or tisagenlecleucel) through Day 26, with guidelines for use of other CRS/ICANS interventions. Importantly, itacitinib did not impact IEC therapy efficacy (objective response rate at 6 months: 39.1% for itacitinib 200 mg bid vs 26.1% for placebo). Trial registration: clinicaltrials.gov; #NCT04071366."

Journal • P2 data • Hematological Disorders • Hematological Malignancies • Oncology

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 primary completion date: Jan 2026 ➔ Jun 2026

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

An Open-Label Phase 1/2 Study of Itacitinib in Combination With Osimertinib in Subjects With Non-Small Cell Lung Cancer (clinicaltrials.gov) - P1/2 | N=59 | Completed | Sponsor: Incyte Corporation | Active, not recruiting ➔ Completed

Trial completion • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Itacitinib in advanced hepatocellular cancer following first line therapy. (PubMed, NPJ Precis Oncol) - "Itacitinib either as second- or third-line therapy showed promising activity. We identified a transcriptomic signature predictive of response."

IO biomarker • Journal • Dermatology • Fatigue • Hematological Disorders • Hepatocellular Cancer • Hepatology • Liver Cancer • Oncology • Solid Tumor • Thrombocytopenia

Impact of Itacitinib Exposure on Immune Reconstitution and Cytokine Profile Following HLA-Matched Allogeneic Hematopoietic Cell Transplantation (HCT) with Tacrolimus, Sirolimus, and Itacitinib GVHD Prophylaxis (TCT-ASTCT-CIBMTR 2026) - P2 | "Evaluate the immune reconstitution following HLA-matched allogeneic hematopoietic cell transplantation with tacrolimus, sirolimus, and itacitinib GVHD prophylaxis 3. Interpret the relationship between itacitinib exposure, T cells subsets, and GVHD biomark."

Acute Graft versus Host Disease • Graft versus Host Disease • Immunology • Transplantation • CD4 • CD8 • IL6 • REG3A • TNFRSF1A

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

JAKaL: Phase Ib study of itacitinib, a selective JAK1 inhibitor, for the management of advanced stage hepatocellular cancer after failure of first line therapy (LCS 2026) - "Conclusion Itacitinib either as second- or third-line therapy showed promising activity. We identified a transcriptomic signature predictive of response."

Clinical • IO biomarker • Metastases • P1 data • Gastrointestinal Cancer • Hepatocellular Cancer • Liver Cancer • Oncology • Solid Tumor

Phase II Study of Pembrolizumab and Itacitinib for First Line Treatment of Metastatic NSCLC Expressing PD-L1 (IASLC-WCLC 2022) - "Treatment-naïve pts with mNSCLC and PD-L1 expression ≥50% treated with pembrolizumab and a brief course of JAK inhibition starting at week 6 of treatment resulted in an ORR of 62% at 12 weeks and mPFS of 23.4 months. This novel combination was well tolerated. Interferon signaling modulation through JAK1 inhibition may help prevent resistance to anti-PD1 therapy and should be studied further in a randomized trial."

Clinical • IO biomarker • P2 data • Dermatology • Immune Modulation • Inflammation • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pneumonia • Solid Tumor • JAK2 • PD-L1

Phase II Study of Pembrolizumab and Itacitinib for Patients with Metastatic NSCLC Expressing PD-L1: Long-Term Follow up (IASLC-WCLC 2024) - P2 | "Conclusions : Treatment-naïve pts with mNSCLC and PD-L1 expression ≥50% treated with pembrolizumab and a brief course of JAK inhibition achieved an ORR of 62% at 12 weeks and improvement in mPFS and mOS compared to historical controls (Keynote 24: mPFS 10.3 mo, mOS 30 mo). Interferon signaling modulation through JAK1 inhibition may help prevent resistance to anti-PD1 therapy and should be studied further in a randomized trial."

Clinical • IO biomarker • Metastases • P2 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • JAK2 • PD-L1

HLH-JAK: Treatment of Non Severe Hemophagocytosis Lymphohistiocytosis With ITACITINIB (clinicaltrials.gov) - P2 | N=35 | Completed | Sponsor: Assistance Publique - Hôpitaux de Paris | Recruiting ➔ Completed | N=63 ➔ 35 | Trial completion date: Feb 2024 ➔ Oct 2025 | Trial primary completion date: Nov 2023 ➔ Apr 2025

Enrollment change • Trial completion • Trial completion date • Trial primary completion date • Immunology • Rare Diseases

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