Itari (linperlisib) / Shanghai YingLi Pharma, Jiangsu Hengrui Pharma - LARVOL DELTA

Synergistic Remission of refractory cutaneous T-cell lymphoma by linperlisib plus venetoclax via targeting the PI3K/AKT/CREB-BCL-2/MCL-1 signaling axis. (ASH 2025) - " We report a 67-year-old woman with multiply relapsed pcALCL refractory to CHOP, CHOP plus brentuximab vedotin (BV), and three courses of total skin electron beam therapy (TSEBT), who subsequently initiated combination therapy with linperlisib (PI3Kδ inhibitor) and venetoclax (BCL-2 inhibitor). In this case, dual PI3Kδ and BCL-2 blockade achieved durable remission after failure of all conventional therapies. Linperlisib suppresses BCL-2/MCL-1 expression by inhibiting the PI3K/AKT/CREB axis, synergizing with venetoclax to overcome resistance. This combination represents a novel therapeutic strategy for achieving durable remission in relapsed pcALCL."

Clinical • IO biomarker • Cutaneous T-cell Lymphoma • Dermatology • Hematological Malignancies • Lymphoma • Mantle Cell Lymphoma • Mycosis Fungoides • Non-Hodgkin’s Lymphoma • Sezary Syndrome • T Cell Non-Hodgkin Lymphoma • BCL2 • MCL1 • PIK3CD • TNFRSF8

Efficacy and safety of linperlisib combined with azacitidine in patients with lymphoma (ASH 2025) - "Observed adverse events included: anemia (n=12, 85.7%), pneumonia (n=10, 71.4%), thrombocytopenia (n=6, 42.9%), febrile neutropenia (n=6, 42.9%), liver function impairment (n=4, 28.6%), nausea/vomiting (n=2, 14.3%), diarrhea (n=1, 7.1%), and hypersensitivity (n=1, 7.1%). Conclusion : The combination of linperlisib and azacitidine demonstrated promising efficacy and a manageable safety profile in patients with lymphoma."

Clinical • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Immunology • Infectious Disease • Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Peripheral T-cell Lymphoma • Pneumonia • Respiratory Diseases • T Cell Non-Hodgkin Lymphoma • Thrombocytopenia

The oral PI3Kdelta inhibitor Linperlisib and Obinutuzumab as response-dependent, first-line regimen for marginal zone lymphoma: A prospective single-arm Phase Ib/II Study (ASH 2025) - P1/2 | "Conclusion Front-line treatment with Linperlisib and Obinutuzumab in MZL demonstrated encouraging early efficacy with a manageable safety profile. Further enrollment and follow-up are ongoing to confirm these preliminary findings and better define the role of this response-adapted strategy in the first-line setting for MZL."

Clinical • P1/2 data • B Cell Lymphoma • Follicular Lymphoma • Indolent Lymphoma • Infectious Disease • Interstitial Lung Disease • Lymphoma • Marginal Zone Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Pneumonia • Respiratory Diseases • PIK3CD

Single center updated analysis of patients with Relapsed/Refractory peripheral T-cell lymphoma treated with linperlisib. (ASH 2025) - P2 | "In a heavily pretreated, with r/r PTCL/CTCL, linperlisib demonstrated robust activity withearly and durable responses—especially in AITL—and a manageable safety profile, including with step-down dosing. These findings support further exploration of Linperlisib in US population and use ofmaintenance dosing strategy. Overall the safety profile was manageable, and treatment-related AEs weregenerally reversible or non-life-threatening."

Clinical • Constipation • Cutaneous T-cell Lymphoma • Follicular Lymphoma • Gastroenterology • Gastrointestinal Disorder • Hematological Malignancies • Immunology • Infectious Disease • Lymphoma • Pancreatitis • Peripheral Neuropathic Pain • Peripheral T-cell Lymphoma • Respiratory Diseases • T Cell Non-Hodgkin Lymphoma • PIK3CD

Efficacy and safety results of linperlisib in adult patients with primary immune thrombocytopenia (ITP) (ASH 2025) - P1/2 | "Linperlisib was well tolerated in adult patients with relapsed/refractory ITP. Linperlisib 40mgQD demonstrated durable, and clinically significant platelet responses in all subgroups with pretreatedITP. A randomized phase 3 study will be continued to further assess the durable clinical benefits oflinperlisib in adult patients with relapsed/refractory ITP."

Clinical • Dyslipidemia • Hematological Disorders • Immune Thrombocytopenic Purpura • Immunology • Metabolic Disorders • Thrombocytopenia • Thrombocytopenic Purpura • PIK3CD

Preliminary efficacy and safety of golidocitinib in relapsed/refractory T cell and NK cell large granular lymphocyte leukemia (ASH 2025) - P2 | "Immunosuppressive therapy remains the standard first linetreatment, including methotrexate, cyclosporine A, and cyclophosphamide...Sixpatients had failed three or more prior lines including PI3Kδ inhibitor linperlisib and JAK1/2 inhibitorruxolitinib...Golidocitinib monotherapy demonstrates compelling clinical activity, including 100% response amongSTAT3 wild type evaluable patients, and a favorable safety profile in heavily pretreated r/r T-LGLLpatients. These results support its further development in this population with unmet medical needs."

Clinical • Autoimmune Hemolytic Anemia • Cutaneous T-cell Lymphoma • Gastrointestinal Disorder • Hematological Malignancies • Herpes Zoster • Immunology • Indolent Lymphoma • Leukemia • Lymphoma • Natural Killer/T-cell Lymphoma • Neutropenia • Peripheral T-cell Lymphoma • T Cell Non-Hodgkin Lymphoma • Thrombocytopenia • Varicella Zoster • PIK3CD • STAT3

CHOP combined with linperlisib or chidamide may decrease the risk of mortality of monomorphic epitheliotropic intestinal T-cell lymphoma: A single-center cohort study (ASH 2025) - "Based on present data, the most frequently mutated pathways in MEITL patients was JAK-STAT pathway. Surgery combined with chemotherapy may prolong their overall survival. And CHOPcombined with HDAC or PI3Kδ inhibitors may decrease risk of mortality of them."

Clinical • CNS Disorders • Hematological Malignancies • Lymphoma • Peripheral T-cell Lymphoma • T Cell Non-Hodgkin Lymphoma • CD20 • CD7 • ITGAE • JAK3 • NCAM1 • PIK3CD • SETD2 • STAT5B • TIA1 • TNFRSF8

PIM1 mutation drives ANXA2 membrane relocalization and promotes lymphomagenesis through PI3K/AKT/mTOR pathway in DLBCL (ASH 2025) - "In particular, thePIM1L184F mutation promoted cell proliferation and was resistant to doxorubicin in vitro and showedfaster tumor growth in vivo. Additionally, the high-throughput drug screening demonstrated thatthe PIM1L184F mutated cells were more sensitive to the PI3K inhibitor YY20394. PIM1 inhibitor SMI-4acombined with YY20394 showed synergistic antitumor effects both in vitro and in vivo.ConclusionsTaken together, these findings not only shed light on an innovative regulatory mechanismfor how PIM1L184F mutation contributes to the pathogenesis of DLBCL but also provide a potentialtherapeutic strategy for effectively managing DLBCL patients harboring PIM1L184F mutation."

IO biomarker • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • ANXA2 • PIM1 • TLR4

Linperlisib Combined With Chidamide in Patients With PTCL (clinicaltrials.gov) - P1/2 | N=134 | Recruiting | Sponsor: Yanyan Liu | N=100 ➔ 134 | Trial completion date: May 2026 ➔ Dec 2027 | Trial primary completion date: Dec 2025 ➔ May 2027

Enrollment change • Trial completion date • Trial primary completion date • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Peripheral T-cell Lymphoma • T Cell Non-Hodgkin Lymphoma

Low-Dose Linperlisib Achieves Rapid Hematologic Response in a Patient with Pure Red Cell Aplasia and Severe Renal Insufficiency: A Case Report. (PubMed, Turk J Haematol) - No abstract available

Journal • Hematological Disorders • Nephrology • Renal Disease

Venetoclax Enhances Human Γδt Cells Anti-Leukemia Immunity through Metabolic Reprogramming (ASH 2024) - "Results : Among several pharmacological agents, such as Venetoclax, Enasidenib, Azacytine, Selinexor, Decitabine, Chidamise, Linperlisib and Cytarabine, Venetoclax treatment significantly enhanced the anti-tumor efficacy of γδT cells against the γδT cell-resistant AML cell line and patient-derived cells, achieving a 49.21% killing efficiency in venetoclax-treated γδT cells compared to 5.06% with untreated cells. The ability of venetoclax to potentiate the natural cytotoxic functions of γδT cells and promote a metabolic state conducive to long-lasting cytotoxicity offers a dual mechanism of action that could overcome some of the traditional challenges faced in targeting AML. The convergence of cellular therapy with targeted drug treatment, as evidenced by the efficacy of venetoclax in our research, represents a novel and exciting direction in cancer immunotherapy."

IO biomarker • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • CD69 • IL2RA • NKG2D

Subgroup Analysis from a Phase 2, Single-Arm Trial of the Oral PI3Kδ Inhibitor Linperlisib in Patients with Relapsed or Refractory Follicular Lymphoma (ASH 2023) - P2 | "Although minor differences were observed in this subgroup, their significance is limited due to the small sample sizes and probably do not alter the overall clinical benefit of linperlisib. Nevertheless, these findings warrant further investigation."

Clinical • P2 data • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Oncology • PIK3CD

Dose Adjustments of Linperlisib in Relapsed or Refractory Follicular Lymphoma: A Post-Hoc Analysis of a Pivotal Phase II Study (ASH 2023) - "Our post-hoc analysis reveals that elderly patients (≥60 years old) have reduced tolerance to linperlisib, necessitating more frequent dose adjustments due to AEs. Notably, treatment discontinuation results in inferior DOR and PFS, while dose adjustments or suspensions yield comparable DOR and PFS to full-dose treatment, suggesting that tolerability-guided dose modification effectively reduces AEs without sacrificing therapeutic efficacy."

P2 data • Retrospective data • Follicular Lymphoma • Gastroenterology • Gastrointestinal Disorder • Hematological Malignancies • Immunology • Infectious Disease • Interstitial Lung Disease • Lymphoma • Oncology • Pneumonia • Respiratory Diseases • PIK3CD

Linperlisib in Conjunction with Gemcitabine and Oxaliplatin in Relapsed/Refractory Diffuse Large B-Cell Lymphoma: A Multicenter, Single-Arm Phase Ib/II Study (ASH 2023) - P1b/2 | "The combination of linperlisib with GEMOX exhibits a favorable safety profile and promising clinical efficacy in patients with r/r DLBCL who have received a median of two prior systemic therapies. These findings support the potential role of linperlisib combined with GEMOX as an active and safe therapeutic option for patients with r/r DLBCL, and set a foundation for further research into linperlisib's potential in combination with other treatment regimens."

Clinical • P1/2 data • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • PIK3CD

A Phase Ib Study of Linperlisib Monotherapy in Patients with Relapsed or Refractory B-Cell Malignancies (ASH 2023) - "In summary, our study underscores the significant potential of linperlisib in providing broad anti-tumor activity across a range of r/r B-cell malignancies, including DLBCL, MCL, MZL, FL, and SLL/CLL. These encouraging results justify further investigation of linperlisib, both as a monotherapy and in combination with other therapeutic agents. It is hoped that these findings will help evolve and enhance our treatment strategies for B-cell malignancies and ultimately improve patient outcomes."

Clinical • Monotherapy • P1 data • B Cell Lymphoma • Chronic Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • Indolent Lymphoma • Infectious Disease • Leukemia • Lymphoma • Mantle Cell Lymphoma • Marginal Zone Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Pneumonia • Respiratory Diseases • PIK3CD

PI3Kδ Inhibitor Linperlisib As a ≥ 3-Line Treatment for Relapsed or Refractory Follicular Lymphoma: A Subgroup Analysis of a Phase II, Single-Arm, Open-Label Trial (ASH 2023) - P2 | "The AEs were well-tolerated. Further trials with large-scale samples were warranted."

Clinical • P2 data • Dyslipidemia • Follicular Lymphoma • Hematological Disorders • Hematological Malignancies • Hypertriglyceridemia • Indolent Lymphoma • Infectious Disease • Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Oncology • Pneumonia • Respiratory Diseases • PIK3CD

A Multicenter Phase2 Trial of Linperlisib in Relapsed or Refractory Peripheral T/NK Cell Lymphomas (ASH 2023) - "As in previous lymphoma studies with linperlisib, a high proportion of responses were CRs, and responses were observed across almost all PTCL subtypes. A phase 2 r/r PTCL and CTCL trial in the US/EU is ongoing."

Clinical • P2 data • Anemia • B Cell Lymphoma • Cardiovascular • Cutaneous T-cell Lymphoma • Diabetes • Dyslipidemia • Follicular Lymphoma • Gastroenterology • Gastrointestinal Disorder • Heart Failure • Hematological Disorders • Hematological Malignancies • Hypertriglyceridemia • Immunology • Infectious Disease • Leukopenia • Lymphoma • Metabolic Disorders • Natural Killer/T-cell Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Oncology • Peripheral T-cell Lymphoma • Pneumonia • Respiratory Diseases • Thrombocytopenia

A Phase Ib/II Clinical Trial of Linperlisib Combined with Camrelizumab and Pegaspargase in Advanced or Relapsed/Refractory NK/T-Cell Lymphoma: Analysis of the Phase Ib Part (ASH 2024) - P1/2 | "Now, the phase II study is ongoing.Conclusions : Linperlisib combined with camrelizumab and pegaspargase was well tolerated and efficacious in patients with advanced or relapsed/refractory NK/T-cell Lymphoma. The efficacy and safety profiles will be verified in the ongoing phase II study."

Clinical • Metastases • P1/2 data • Hemophagocytic lymphohistiocytosis • Infectious Disease • Leukopenia • Lymphoma • Natural Killer/T-cell Lymphoma • T Cell Non-Hodgkin Lymphoma • PIK3CD

Linperlisib in Combination with CHOP for Newly-Diagnosed Peripheral T-Cell Lymphoma: Preliminary Results from the Phase 1b/2 Linch Study (ASH 2024) - P1/2, P2 | "In phase 1b, 6 patients received 6 cycles of L-CHOP regimen : linperlisib 80 mg orally once daily on days 1 to 21, cyclophosphamide 750 mg/m² intravenously on day 1, doxorubicin 50 mg/m² intravenously on day 1, vincristine 1.4 mg/m² intravenously on day 1, and prednisone 100 mg orally once daily on days 1 to 5 of each 21-day cycle. Of these SAEs, fever was judged to be unrelated to the treatment. SAEs were finally relieved by discontinuation of linperlisib and symptomatic treatment.ConclusionsThese preliminary findings indicate the feasibility of PI3Kδ inhibitor linperlisib combined with CHOP regimen as first-line treatment for patients with newly-diagnosed PTCL."

Combination therapy • P1/2 data • Anemia • Febrile Neutropenia • Follicular Lymphoma • Hepatosplenic T-cell Lymphoma • Infectious Disease • Leukopenia • Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Peripheral T-cell Lymphoma • Pneumonia • Respiratory Diseases • T Cell Non-Hodgkin Lymphoma • Thrombocytopenia • PIK3CD

Linperlisib Combined with CHOP Regimen Followed By Autologous Hematopoietic Stem Cell Transplantation and Linperlisib Monotherapy Maintenance for Newly Diagnosed Nodal T-Follicular Helper Cell Lymphoma Patients: A Phase II Trial (ASH 2024) - P2 | "Standard cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) or CHOP-like regimens often yield suboptimal outcomes. Treatment discontinuations due to TRAEs occurred in 13.33% (2/15) of patients.Conclusion : Linperlisib combined with CHOP shows promising efficacy and manageable safety in newly diagnosed nTFHL patients. This study is ongoing, and further long-term data are anticipated."

Clinical • Monotherapy • P2 data • Bone Marrow Transplantation • Follicular Lymphoma • 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 • Thrombocytopenia • Transplantation • PIK3CD

A Phase II Clinical Study Exploring the Safety and Efficacy of the Oral PI3Kδ Inhibitor, Linperlisib, in Relapsed Refractory T Cell Lymphoma (ASH 2024) - P2 | "With a high durable CR rate, the clinical benefit of linperlisib in non-Asian pts merits further investigation. A global r/r PTCL Phase 3 study is planned."

Clinical • P2 data • B Cell Lymphoma • B Cell Non-Hodgkin Lymphoma • Cutaneous T-cell Lymphoma • Dermatology • Dyslipidemia • Follicular Lymphoma • Gastroenterology • Gastrointestinal Disorder • Hematological Disorders • Hematological Malignancies • Hypertriglyceridemia • Immunology • Infectious Disease • Lymphoma • Mycosis Fungoides • Neutropenia • Non-Hodgkin’s Lymphoma • Oncology • Peripheral T-cell Lymphoma • Pneumonia • Respiratory Diseases • Sezary Syndrome • T Cell Non-Hodgkin Lymphoma • Thrombocytopenia • PIK3CD

Phosphorylation-Dependent ANXA2 Relocation on the Membrane and TLR4 Engagement: A Novel Signaling Axis Promoted By PIM1 Mutation in Diffuse Large B Cell Lymphoma (ASH 2024) - "Notably, the PIM1 inhibitor SMI-4a demonstrated synergistic antitumor effects with the PI3K inhibitor Linperlisib in vitro and in vivo, offering a potentially more effective therapeutic strategy for patients harboring PIM1 mutations. Conclusions : Taken together, we identify recurrent somatic PIM1 L184F mutations that may contribute to the pathogenesis of DLBCL and establish the rationale for therapeutic strategies aimed at targeting the oncogenic pathway activated in PIM1-mutated DLBCL."

B Cell Lymphoma • B Cell Non-Hodgkin Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • ANXA2 • PIM1 • TLR4

Phase II Study Evaluating the Combination of Linperlisib, Azacitidine, and Liposomal Mitoxantrone in Treatment-Naïve Nodal TFH Cell Lymphoma (ChiCTR) - P2 | N=30 | Not yet recruiting | Sponsor: The First Affiliated Hospital of Soochow University; The First Affiliated Hospital of Soochow University

New P2 trial • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • T Cell Non-Hodgkin Lymphoma

Combination Therapy With Tazemetostat in Relapsed and Refractory Peripheral T-cell Lymphoma (clinicaltrials.gov) - P1/2 | N=48 | Not yet recruiting | Sponsor: Ruijin Hospital

New P1/2 trial • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Peripheral T-cell Lymphoma • T Cell Non-Hodgkin Lymphoma

In vitro antitumor effects of PI3K inhibitor linperlisib (YY-20394) on acute myeloid leukemia cells. (PubMed, Hematology) - "Interestingly, YY20394 did not exert its anti-leukemic effects through modulation of the PI3 K/Akt/mTOR Signaling pathway, suggesting that alternative molecular mechanisms may be involved. YY20394 has a favorable inhibitory effect and significant pro-apoptotic effect on the proliferation of AML cells, which suggests that it has some potential for the treatment of AML."

Journal • Preclinical • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology