parsaclisib (INCB50465) / Incyte, Innovent Biologics - LARVOL DELTA

Efficacy and Safety of Add-on Parsaclisib to Ruxolitinib Therapy in Myelofibrosis Patients With Suboptimal Response to Ruxolitinib: Final Results From a Phase 2 Study (ASH 2022) - P2 | "Final results from the phase 2 study demonstrate improvement in symptoms and SV with add-on parsaclisib in patients with MF having a suboptimal response to ruxolitinib. All daily dosing regimens were more efficacious than daily/weekly dosing. Combination therapy was associated with limited grade 3/4 AEs and TEAE-related discontinuations."

Clinical • P2 data • Endocrine Disorders • Fatigue • Gastroenterology • Gastrointestinal Disorder • Herpes Simplex • Immunology • Infectious Disease • Myelofibrosis • Myeloproliferative Neoplasm • Pneumonia • Polycythemia Vera • Pulmonary Disease • Respiratory Diseases • Thrombocytopenia • Thrombocytosis • PIK3CD

A PHASE 1 STUDY EVALUATING SAFETY AND EFFICACY OF PARSACLISIB IN COMBINATION WITH BENDAMUSTINE + OBINUTUZUMAB IN PATIENTS WITH RELAPSED OR REFRACTORY FOLLICULAR LYMPHOMA (CITADEL-102) (EHA 2022) - P1 | "Background Patients (pts) with follicular lymphoma (FL) generally respond well to first-line CD20-targeted therapies, such as obinutuzumab or rituximab-based regimens. Median DOR, PFS, and OS were not reached. Conclusion Parsaclisib in combination with bendamustine + obinutuzumab appears to have a manageable safety profile and demonstrated promising efficacy in pts with R/R FL."

Clinical • Combination therapy • P1 data • Febrile Neutropenia • Follicular Lymphoma • Hematological Disorders • Hematological Malignancies • Infectious Disease • Lymphoma • Metabolic Disorders • Neutropenia • Novel Coronavirus Disease • Oncology • Pneumonia • Respiratory Diseases • Thrombocytopenia • PIK3CD

Add-on parsaclisib for patients with myelofibrosis and suboptimal response to ruxolitinib: a randomized phase 3 study. (PubMed, Oncologist) - P3 | "Study results suggested adding parsaclisib to stable-dose ruxolitinib was unlikely to offer clinically meaningful benefits. Further research is needed on the potential of JAK and PI3K inhibitor-based combination therapy for patients with myelofibrosis."

Clinical • Journal • P3 data • Cytomegalovirus Infection • Gastroenterology • Gastrointestinal Disorder • Infectious Disease • Myelofibrosis • PIK3CD

A Phase 1/1b Study of Parsaclisib Plus Standard Immunochemotherapy for Newly Diagnosed High-Risk Diffuse Large B-Cell Lymphoma (ASH 2024) - "Our group previously reported that addition of the mTOR inhibitor everolimus to R-CHOP resulted in excellent efficacy in the Alliance N1085 trial (Witzig TE et al, Blood Cancer J, 2017, 7(6) : e576), with 23 of 24 patients achieving event-free survival at 24 months (EFS24), supporting further investigation of PI3K/mTOR targeting in DLBCL...Conclusions : Addition of the PI3K inhibitor parsaclisib to R-CHOP or Pola-R-CHP immunochemotherapy is considered safe in patients with newly diagnosed DLBCL. Combination of parsaclisib and standard immunochemotherapy resulted in high ORR and CR rate and encouraging preliminary PFS and OS outcomes patients with high-risk DLBCL. These data support further investigation of PI3K/mTOR targeting in newly diagnosed DLBCL in future trials."

IO biomarker • P1 data • Anemia • B Cell Lymphoma • B Cell Non-Hodgkin Lymphoma • Constipation • Diffuse Large B Cell Lymphoma • Fatigue • Febrile Neutropenia • Gastroenterology • Gastrointestinal Disorder • Hematological Disorders • Hematological Malignancies • High-grade B-cell lymphoma • Leukopenia • Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Oncology • Thrombocytopenia • BCL2 • BCL6 • MYC

Safety and efficacy of parsaclisib in combination with obinutuzumab and bendamustine in patients with relapsed or refractory follicular lymphoma (CITADEL-102): A phase 1 study. (PubMed, Hematol Oncol) - P1 | "Seventeen patients (65.4%) had a complete response and 3 patients (11.5%) had a partial response, for an objective response rate of 76.9%. Overall, results from CITADEL-102 suggest that the combination of parsaclisib with obinutuzumab and bendamustine did not result in unexpected safety events, with little evidence of synergistic toxicity, and demonstrated preliminary efficacy in patients with R/R FL who progressed following prior rituximab-containing regimens."

Clinical • Combination therapy • Journal • P1 data • Febrile Neutropenia • Follicular Lymphoma • Gastroenterology • Gastrointestinal Disorder • Hematological Disorders • Hematological Malignancies • Immunology • Lymphoma • Neutropenia • Oncology • Oropharyngeal Cancer • Thrombocytopenia • CD20 • PIK3CD

A PHASE 1 STUDY OF PARSACLISIB IN COMBINATION WITH RITUXIMAB, BENDAMUSTINE + RITUXIMAB, OR IBRUTINIB IN PATIENTS WITH PREVIOUSLY TREATED B-CELL LYMPHOMA (CITADEL-112): PRELIMINARY SAFETY RESULTS (EHA 2022) - P1 | "Parsaclisib dose interruption or dose reduction due to TEAEs occurred in 75.0% and 18.8% of pts, respectively, in Tmt A; 66.7% and 27.8% of pts, respectively, in Tmt B; and 56.3% and 18.8% of pts, respectively, in Tmt C. Conclusion Parsaclisib 20 mg QD for 8 weeks followed by 20 mg QW can be safely combined with RIT, RIT + BEN, or IBR in pts with R/R B-cell lymphomas. The tolerability profile of the combination regimens was manageable, with no unexpected safety concerns."

Clinical • Combination therapy • P1 data • Acute Kidney Injury • Anemia • Atrial Fibrillation • Bone Marrow Transplantation • Cardiovascular • Diffuse Large B Cell Lymphoma • Hematological Disorders • Hematological Malignancies • Infectious Disease • Interstitial Lung Disease • Lymphoma • Marginal Zone Lymphoma • Nephrology • Neutropenia • Non-Hodgkin’s Lymphoma • Novel Coronavirus Disease • Oncology • Pain • Pneumonia • Pulmonary Disease • Renal Disease • Respiratory Diseases • Transplantation • PIK3CD

Rollover Study to Provide Continued Treatment for Participants With B-Cell Malignancies Previously Enrolled in Studies of Parsaclisib (INCB050465) (clinicaltrials.gov) - P2 | N=112 | Active, not recruiting | Sponsor: Incyte Corporation | Trial completion date: Sep 2027 ➔ Nov 2026 | Trial primary completion date: Sep 2027 ➔ Nov 2026

Trial completion date • Trial primary completion date • Hematological Malignancies • Oncology

J-MIND: To Assess the Safety and Tolerability of Tafasitamab Alone or in Combination With Other Drugs in Japanese Participants With Non-Hodgkins Lymphoma (NHL) (clinicaltrials.gov) - P1/2 | N=72 | Active, not recruiting | Sponsor: Incyte Biosciences Japan GK | Trial primary completion date: Dec 2026 ➔ Jul 2025

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

The Path Forward in MF: Small Molecules in the Limelight. (PubMed, Cancers (Basel)) - "However, a substantial percentage of patients fail to achieve sustained benefit, are intolerant, or become refractory; real-world and clinical trial data indicate that approximately half of treated patients discontinue ruxolitinib treatment within 3 years and up to approximately 75% within 5 years, with poor outcomes after discontinuation (median survival in several series is approximately 12-14 months)...These include agents targeting telomerase (imetelstat), epigenetic regulation via BET inhibition (pelabresib/CPI-0610), the MDM2-p53 axis (navtemadlin/KRT-232), erythroid maturation and the bone marrow microenvironment (luspatercept), PI3K signaling (parsaclisib), and PIM inhibitors (nuvisertib). Early clinical data show promising results for symptom and splenic control in specific settings and, importantly, suggest potential disease-modifying activity (improvements in marrow fibrosis and molecular responses) for some compounds. This review summarizes the biological..."

Journal • Review • Chronic Eosinophilic Leukemia • Fibrosis • Hematological Disorders • Immunology • Myelofibrosis • Myeloproliferative Neoplasm • Oncology

Tafasitamab as Monotherapy or in Combination in Japanese Patients With B-Cell Non-Hodgkin Lymphoma: Results From the Phase 1b J-MIND Study. (PubMed, Cancer Sci) - P1/2 | "Patients received tafasitamab starting at 12 mg/kg qw (Group 1, n = 6), tafasitamab + lenalidomide starting at 25 mg qd for ≤ 12 cycles (Group 3, n = 6), tafasitamab + parsaclisib starting at 20 mg qd (Days 1-56) then 2.5 mg qd (Group 4, n = 6), or tafasitamab + lenalidomide combined with R-CHOP for ≤ 6 cycles (Group 5, n = 6). However, results should be interpreted with caution due to the small sample size, with further studies warranted to confirm these findings. Trial Registration: NCT04661007; jRCT2031200357."

Journal • Monotherapy • P1 data • B Cell Lymphoma • B Cell Non-Hodgkin Lymphoma • Constipation • Diffuse Large B Cell Lymphoma • Febrile Neutropenia • Gastroenterology • Gastrointestinal Disorder • Hematological Malignancies • Hepatology • Leukopenia • Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Thrombocytopenia

topMIND: A Study Evaluating Safety, PK, and Efficacy of Tafasitamab and Parsaclisib in Participants With Relapsed/Refractory Non Hodgkin Lymphoma (R/R NHL) or Chronic Lymphocytic Leukemia (CLL) (clinicaltrials.gov) - P1/2 | N=54 | Terminated | Sponsor: Incyte Corporation | Completed ➔ Terminated; A business decision was made to discontinue further enrollment. There were no safety concerns that contributed to this decision.

Pan tumor • Trial termination • Chronic Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Leukemia • Lymphoma • Mantle Cell Lymphoma • Marginal Zone Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • BCL2 • BCL6 • CCND1

Feasibility assessment of indirect treatment comparison between off-label rituximab and novel treatments in patients with warm autoimmune hemolytic anemia (ASH 2025) - "Among the clinical trials included, five studied rituximab, in combination with prednisone, prednisolone, ibrutinib, or bortezomib. Three trials studied fostamatinib, while other studied treatments included pegcetacoplan, sovleplenib, parsaclisib, and rilzabrutinib...Future work should consider de novo sources of real-world evidence for rituximab that more closely align with registrational trial characteristics and endpoint definitions. However, aligning timing of endpoint measurements between registration trials and real-world data to match definitions remains challenging."

Clinical • Anemia • Autoimmune Hemolytic Anemia • Hematological Disorders • Immunology

Trial in progress: A study of roginolisib in combination with ruxolitinib in patients with myelofibrosis who are unresponsive to JAK inhibitors (HEMA-MED) (ASH 2025) - P1, P1/2 | "In contrast to the first generation PI3K inhibitors, suchas parsaclisib and umbralisib, roginolisib is a novel, oral, non-ATP competitive, allosteric small moleculeinhibitor of PI3Kδ. The study is currentlyactively enrolling at 8 sites in Italy and Spain.Conclusions. Given the safety profile of roginolisib in patients of the FiH dose study, the combination ofruxolitinib and roginolisib is expected to provide a safe combination treatment in patients with MF whoare no longer responding to JAK inhibition."

Clinical • Combination therapy • Follicular Lymphoma • Hematological Disorders • Hematological Malignancies • Lymphoma • Myelofibrosis • Solid Tumor • Thrombocytosis • PIK3CD

Management of Autoimmune Hemolytic Anemia (ASH 2025) - "For relapsed/refractory patients rituximab has become the preferred second line-therapy, comparing favorably with the traditional splenectomy, which has been progressively abandoned or moved to further lines along with classic immunosuppressors. Several novel treatments are in development for wAIHA, encompassing drugs targeting B-cells (parsaclisib, ibrutinib, rilzabrutinib, zanubrutinib, obexelimab, ianalumab, povetacicept), plasma cells (bortezomib, daratumumab), spleen tyrosine kinase (fostamatinib, sovleplenib), and the neonatal Fc receptor (nipocalimab)."

IO biomarker • Anemia • Autoimmune Hemolytic Anemia • Bone Marrow Transplantation • Hematological Disorders • Immunology • Infectious Disease • HP • SYK

Management of autoimmune hemolytic anemia. (PubMed, Hematology Am Soc Hematol Educ Program) - "Rituximab is now the preferred second-line option for relapsed/refractory patients, comparing favorably with the traditional splenectomy. The latter is increasingly reserved for later lines together with classic immunosuppressants. Several novel treatments are in development for refractory wAIHA, encompassing drugs targeting B-cells (parsaclisib, ibrutinib, rilzabrutinib, zanubrutinib, obexelimab, ianalumab, povetacicept), plasma cells (bortezomib, daratumumab), spleen tyrosine kinase (fostamatinib, sovleplenib), and the neonatal Fc receptor (nipocalimab)."

Journal • Review • Anemia • Autoimmune Hemolytic Anemia • Bone Marrow Transplantation • Complement-mediated Rare Disorders • Hematological Disorders • Immunology • Infectious Disease • Oncology • Paroxysmal Nocturnal Hemoglobinuria • Transplantation • SYK

PI3Kδ Inhibitor Parsaclisib Combined With Chidamide for the Treatment of Relapsed/Refractory Peripheral T-cell Lymphoma (clinicaltrials.gov) - P1 | N=12 | Terminated | Sponsor: Henan Cancer Hospital | Phase classification: P1/2 ➔ P1 | Trial completion date: Feb 2025 ➔ Aug 2025

Phase classification • Trial completion date • Hematological Malignancies • Hepatosplenic T-cell Lymphoma • Lymphoma • Natural Killer/T-cell Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Peripheral T-cell Lymphoma • T Cell Non-Hodgkin Lymphoma • ALK

Characterizing the Clinical, Humanistic, and Economic Burden of Warm Autoimmune Hemolytic Anemia: A Systematic Literature Review and Evidence Gap Assessment (ASH 2024) - "While there are no FDA-approved treatments specifically for wAIHA, treatments evaluated within the set of clinical trials included fostamatinib, rituximab, ibrutinib + rituximab, sovleplenib, parsaclisib, and pulse cyclophosphamide. While wAIHA is a relatively poorly studied disease, available data suggests low Hb levels and associated risks across both clinical trials and real-world study publications, reflecting a high unmet need in this patient population. Patient-reported outcomes, including health-related quality of life measures, should be evaluated with clinical outcomes in future trials and observational studies to facilitate understanding of outcomes that are important to patients."

Clinical • HEOR • Review • Anemia • Autoimmune Hemolytic Anemia • Fatigue • Hematological Disorders • Immunology

Selective PI3Kδ Inhibitor Parsaclisib Combined with HDAC Inhibitor Chidamide in Patients with Relapsed/Refractory Peripheral T-Cell Lymphoma: Preliminary Results of a Phase Ib/Ⅱ Study (ASH 2023) - P1/2 | "Preliminary data demonstrated that selective PI3Kδ Inhibitor parsaclisib with HDACi chidamide was tolerable and produced promising responses in r/r PTCL, including patients previously exposed to chidamide. This trial is currently ongoing."

Clinical • Cytomegalovirus Infection • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukopenia • Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Oncology • Peripheral T-cell Lymphoma • Pneumonia • Respiratory Diseases • T Cell Non-Hodgkin Lymphoma • PIK3CD

Bullous Pemphigoid Develops Independently of DAP12. (PubMed, Biomolecules) - "In addition, pharmacological inhibition of PI3Kδ, a downstream kinase of the DAP12/TREM pathway, did not affect disease progression in anti-Col17 IgG-induced BP. Collectively, these findings indicate that while DAP12 signaling modulates local immune cell composition, the DAP12/TREM1/2-axis does not influence overall disease activity in experimental BP."

Journal • Bullous Pemphigoid • Dermatology • Dermatopathology • Immunology • PIK3CD

Safety and Efficacy of Parsaclisib in Combination with Rituximab in Patients with Previously Untreated Indolent B-Cell Lymphoma: Primary Analysis from a Phase 2 Study (REPLY) (ASH 2023) - P2 | "The combination of parsaclisib with rituximab showed a deep and durable response, with a favorable safety profile and generally good tolerability in patients with previously untreated indolent B-Cell Lymphoma."

Clinical • Combination therapy • IO biomarker • P2 data • Anemia • B Cell Lymphoma • B Cell Non-Hodgkin Lymphoma • Extranodal Marginal Zone Lymphoma • Follicular Lymphoma • Hematological Disorders • Hematological Malignancies • Hepatitis B • Hepatology • Human Immunodeficiency Virus • Immunology • Indolent Lymphoma • Infectious Disease • Lymphoma • Marginal Zone Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Oncology • BCL2 • MYC

Targeting the Hypoxic Microenvironment in Cutaneous Chronic Graft-Versus-Host Disease through PI3Kδ Inhibition (ASH 2024) - "We tested the PI3Kδ inhibitor (PI3Kδi, Parsaclisib) in the Scl-cGVHD model, the major MHC-mismatched model (C57BL/6→BALB/c) and the Xeno-GVHD model...Remarkably, PI3Kδ inhibition reversed skin hypoxia, prevented the development of pathogenic TLS, and ameliorated cGVHD histopathology, suggesting PI3Kd inhibition emerges as a promising therapeutic approach, alleviating disease symptoms and addressing fundamental mechanisms of disease progression. These insights pave the way for innovative treatments targeting the hypoxic milieu in cutaneous cGVHD."

Alopecia • Bone Marrow Transplantation • Chronic Graft versus Host Disease • Fibrosis • Graft versus Host Disease • Immunology • CD4 • CD8 • HIF1A • IL13 • PIK3CD

Autoimmune complications of lymphoproliferative diseases (ICML 2025) - "Moreover, several drugs may be responsible for immune-mediated cytopenias, including several antibiotics (ceftriaxone, piperacillin, rifampin, nafcillin, erythromycin, ticarcillin, trimethoprim, sulfamethoxazole), and various other drugs (procainamide, quinine, phenacetin, diclofenac, cimetidine, hydrochlorothiazide, chlorpropamide) [8]...Ibrutinib, through the inhibition of autoantibodies producing B-cells and restoration of T-cell homeostasis seems safe, while some case reports of autoimmune diseases have been reported for idelalisib (autoimmune hepatitis, colitis) and venetoclax (AIHA) [5, 6]...They included nivolumab, followed by pembrolizumab, ipilimumab, and atezolizumab...In particular, in CLL several therapies have been reported effective in refractory cytopenias: alemtuzumab single agent, the combinations ibrutinib-rituximab, bendamustine-rituximab, and rituximab–cyclophosphamide-dexamethasone [34-37]. Notably, some of the new/experimental treatments for primary..."

IO biomarker • B Cell Lymphoma • Chronic Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Hodgkin Lymphoma • Leukemia • Lymphoma • Lymphoplasmacytic Lymphoma • Marginal Zone Lymphoma • Multiple Myeloma • Non-Hodgkin’s Lymphoma • Oncology • T Cell Non-Hodgkin Lymphoma • Waldenstrom Macroglobulinemia • CTLA4 • HP • IL10 • PD-1 • TGFB1

Parsaclisib Plus the Standard Drug Therapy in Patients With Newly Diagnosed, High Risk Diffuse Large B-cell Lymphoma (clinicaltrials.gov) - P1 | N=50 | Active, not recruiting | Sponsor: Mayo Clinic | Trial completion date: May 2027 ➔ May 2028

Trial completion date • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • High-grade B-cell lymphoma • Indolent Lymphoma • Lymphoma • Marginal Zone Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • BCL2 • BCL6 • CD20 • MYC

Beneath the surface in autoimmune hemolytic anemia: pathogenetic networks, therapeutic advancements and open questions. (PubMed, Front Immunol) - "Glucocorticoids remain the standard first-line therapy for warm AIHA; in contrast, CAD/CAS is increasingly managed with agents targeting B-cell function or complement activation, including rituximab and sutimlimab...Emerging therapeutics targeting the classical complement pathway include novel anti-C1s monoclonal antibodies such as riliprubart, which exhibits an extended half-life due to enhanced affinity for the neonatal Fc receptor. Parallel strategies aim to disrupt B-cell receptor (BCR) signaling cascades, employing Bruton tyrosine kinase (BTK) inhibitors such as ibrutinib, spleen tyrosine kinase (SYK) inhibitors such as fostamatinib and sovleplenib, and phosphoinositide 3-kinase (PI3K) inhibitors such as parsaclisib. Collectively, these advances are reshaping the therapeutic landscape of AIHA toward a precision medicine model guided by mechanistic insights into disease biology. In this review, we delineate the evolving immunopathogenesis of AIHAs and examine..."

Journal • Review • Anemia • Autoimmune Hemolytic Anemia • Complement-mediated Rare Disorders • Hematological Disorders • Immunology • SYK

A Single-arm Phase 2 Prospective Clinical Study of Linprixel in the Treatment of Relapsed/Refractory Autoimmune Hemolytic Anemia (clinicaltrials.gov) - P=N/A | N=22 | Not yet recruiting | Sponsor: Peking Union Medical College Hospital

New trial • Anemia • Autoimmune Hemolytic Anemia • Hematological Disorders • Immunology