Copiktra (duvelisib) / Verastem, CSPC Pharma, Secura Bio, Sanofi, Yakult Honsha - LARVOL DELTA

A PHASE 3 RANDOMIZED TRIAL: DUVELISIB VERSUS INVESTIGATOR CHOICE (GEMCITABINE OR BENDAMUSTINE) IN RELAPSED/REFRACTORY NODAL T-CELL LYMPHOMA WITH T-FOLLICULAR HELPER PHENOTYPE (ICML 2025) - P2, P3 | "DUV monotherapy has demonstrated activity in R/R PTCL, with more pronounced effect in AITL. TERZO will test the hypothesis that DUV monotherapy is associated with improved outcomes compared with GEM or BEN in patients with R/R nTFHL."

Clinical • P3 data • Chronic Lymphocytic Leukemia • Follicular Lymphoma • Hematological Malignancies • Leukemia • Lymphoma • Oncology • Small Lymphocytic Lymphoma • T Cell Non-Hodgkin Lymphoma

A long-lasting PI3Kδ inhibitor zandelisib forms a water-shielded hydrogen bond with p110δ and demonstrates sustained inhibitory effects. (PubMed, Am J Cancer Res) - "The binding kinetics of zandelisib, parsaclisib, idelalisib, and duvelisib to PI3Kδ were evaluated using surface plasmon resonance (SPR) analysis with the BiacoreTM system, and their binding in living cells was confirmed using the NanoBRETTM TE Intracellular Kinase Assay system. The crystal structure of PI3Kδ in complex with zandelisib was determined at 2.5 Å resolution, revealing the benzimidazole group in zandelisib formed a hydrogen bond to the side chain of Lys779 in p110δ, the catalytic subunit of PI3Kδ. These studies demonstrated a longer duration of action of zandelisib compared to the other compounds, which was attributable to the hydrogen bond between zandelisib and Lys779 in p110δ."

Journal • B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • PIK3CD

Secura Bio Announces First Patient Dosed in Phase 3 TERZO Study of COPIKTRA (duvelisib) in Relapsed/Refractory Nodal T-follicular Helper Cell Lymphoma (GlobeNewswire) - "Secura Bio, Inc...announced that the first patient has been dosed in its Phase 3 TERZO study of COPIKTRA (duvelisib) in adults with relapsed or refractory (R/R) nodal T-follicular helper cell lymphoma (nTFHL), a disease where there are currently no well-established standards of care for patients with relapsed or refractory disease.... The company expects to enroll approximately 124 patients with interim data from the study anticipated in early-2027."

P3 data • Trial status • Peripheral T-cell Lymphoma

A Study of Alectinib and Duvelisib in People With Anaplastic Lymphoma Kinase-Positive Anaplastic Large Cell Lymphoma (ALK+ALCL) (clinicaltrials.gov) - P1 | N=30 | Not yet recruiting | Sponsor: Memorial Sloan Kettering Cancer Center

New P1 trial • Non-Hodgkin’s Lymphoma • Oncology

Dermatologic adverse events in patients receiving duvelisib single-agent and combination therapies (SID 2025) - "We noted a lower incidence of DAEs (p=.004) and fewer patients with severe DAEs (p=.04), trending towards shorter duration DAE (p=.08), in patients on duvelisib in combination with romidepsin, bortezomib or ruxolitinib compared to patients on duvelisib alone. Further studies are required to delineate the effects of other agents on incidence and severity of PI3Ki-associated DAEs."

Adverse events • Clinical • Combination therapy • Hematological Malignancies • Leukemia • Lymphoma • Mucositis • Oncology • T Cell Non-Hodgkin Lymphoma

Trial of Duvelisib in Combination With Either Romidepsin or Bortezomib in Relapsed/Refractory T-cell Lymphomas (clinicaltrials.gov) - P1 | N=114 | Active, not recruiting | Sponsor: Memorial Sloan Kettering Cancer Center | Trial completion date: May 2025 ➔ May 2026 | Trial primary completion date: May 2025 ➔ May 2026

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

A Study of Ruxolitinib and Duvelisib in People With Lymphoma (clinicaltrials.gov) - P1 | N=70 | Recruiting | Sponsor: Memorial Sloan Kettering Cancer Center | Trial completion date: Aug 2026 ➔ Aug 2027 | Trial primary completion date: Aug 2026 ➔ Aug 2027

Trial completion date • Trial primary completion date • Cutaneous T-cell Lymphoma • Hematological Malignancies • Hepatosplenic T-cell Lymphoma • Leukemia • Lymphoma • Natural Killer/T-cell Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Prolymphocytic Leukemia • T Cell Non-Hodgkin Lymphoma • T-Cell Large Granular Lymphocyte Leukemia • CD8

Duvelisib Following Chimeric Antigen Receptor T-Cell Therapy (clinicaltrials.gov) - P1 | N=42 | Active, not recruiting | Sponsor: Washington University School of Medicine | Recruiting ➔ Active, not recruiting

Enrollment closed • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Duvelisib Maintenance After Autologous Stem Cell Transplant in T-Cell Lymphomas (clinicaltrials.gov) - P2 | N=17 | Active, not recruiting | Sponsor: Washington University School of Medicine | Trial completion date: Jul 2026 ➔ Dec 2025 | Trial primary completion date: Jul 2026 ➔ Dec 2025

Trial completion date • Trial primary completion date • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • T Cell Non-Hodgkin Lymphoma • Transplantation

HYPOXIA-DRIVEN T CELL-MACROPHAGE-STROMAL CROSSTALK SUSTAINS FIBROSIS IN CUTANEOUS CHRONIC GVHD VIA THE HIF1α/PI3KΔ/IL-13 AXIS (EHA 2025) - "In aggregate, our data indicated that the HIF1α/PI3Kd/IL-13 axis drives persistent fibrosis and immune dysregulation in cutaneous cGVHD under hypoxic conditions, nominating it as a novel target for intervention.To block the PI3K signaling pathway, we first tested Duvelisib, a dual inhibitor of PI3Kg and PI3Kd isoforms, and the PI3Kδ inhibitor Parsaclisib in the multiple murine cGVHD model...Besides, our results HIF1α inhibition effectively protected mice from cGVHD skin pathology, while Dapagliflozin increased HIF1α expression and thus exacerbated the condition... We used a comprehensive systems biology approach, combining spatial transcriptomics, single-cell RNA sequencing, and ultra-multiplex immunofluorescence, to investigate the mechanisms underlying cutaneous cGVHD in both human samples and murine models. Our data reveal a hypoxia-enriched gene signature in cGVHD skin and highlight aberrant macrophage-epidermal crosstalk orchestrated by elevated IL-13 under hypoxic..."

Stroma • Alopecia • Chronic Graft versus Host Disease • Dermatopathology • Fibrosis • Graft versus Host Disease • Immunology • Inflammation • HIF1A • IL13 • IL13RA2 • PIK3CD

A MULTICENTER, OPEN-LABEL, PHASE 3, RANDOMIZED TRIAL OF DUVELISIB VS INVESTIGATOR'S CHOICE (GEMCITABINE OR BENDAMUSTINE) IN RELAPSED/REFRACTORY NODAL T-CELL LYMPHOMA WITH T-FOLLICULAR HELPER PHENOTYPE (EHA 2025) - P2, P3 | "Currently, no agent is approved in the EU/UK for treatment of patients with R/R PTCL, except brentuximab vedotin (BV) for anaplastic large-cell lymphoma (ALCL).The angioimmunoblastic T-cell lymphoma (AITL) cell of origin, a T-follicular helper (TFH) cell, has a set of recurrent gene mutations frequently found in AITL and PTCL-NOS. DUV monotherapy has demonstrated activity in R/R PTCL, with more pronounced effect in AITL. TERZO will test the hypothesis that DUV monotherapy is associated with improved outcomes compared with GEM or BEN in patients with R/R nTFHL."

Clinical • P3 data • Chronic Lymphocytic Leukemia • Follicular Lymphoma • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Peripheral T-cell Lymphoma • Small Lymphocytic Lymphoma • T Cell Non-Hodgkin Lymphoma

Verastem Oncology announces fourth quarter and full-year 2018 financial results and corporate developments (Verastem Press Release) - "Verastem Oncology launched COPIKTRA...in the United States following FDA approval for the treatment of adult patients with relapsed or refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) after at least two prior therapies....Accelerated approval in FL was based on overall response rate and continued approval may be contingent upon verification and description of clinical benefit in confirmatory trials, the first of which is expected to start in 2019."

Launch US • New trial • Chronic Lymphocytic Leukemia • Follicular Lymphoma • Hematological Malignancies • Non-Hodgkin’s Lymphoma • Oncology

Metabolism-related ALDH1B1 acts as potential predictor and therapeutic target for primary gastrointestinal diffuse large B-cell lymphoma. (PubMed, Apoptosis) - "Moreover, cell proliferation assay revealed that the treatment with IGUANA-1, ALDH1B1 inhibitor, suppressed cell proliferation in DLBCL and IGUANA-1 exerted synergistic anti-tumor effects with PI3K inhibitor duvelisib. Additionally, we found that immune scores, ESTIMATE scores, and stromal scores were higher and the immune checkpoints (CTLA-4, PD-1, PD-L1) were down-regulated in patients with high ALDH1B1 expression. Collectively, our study constructed a novel metabolism-related prognostic model and highlighted the potential of metabolism-related gene ALDH1B1 as prognostic biomarker and drug target in PGI-DLBCL, providing new insights for the development of precision therapies in PGI-DLBCL patients."

IO biomarker • Journal • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Gastrointestinal Disorder • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • ALDH1A3 • APOE • PD-1 • PLOD2

Identification of Therapeutic Compounds Targeting Phosphatidylinositol 3-Kinase (PI3K) Through Molecular Docking, Dynamics Simulation, and DFT Calculations. (PubMed, Comput Biol Chem) - "Currently available PI3K inhibitors (like Duvelisib) have significant side effects, highlighting the need for safer therapeutics...This study aims to improve our understanding of ligand-protein dynamics in PI3K inhibition and highlight the potential of gallic acid derivatives in developing safer and more effective PI3K inhibitors for cancer therapy. Our results support further experimental validation of compound 68 and suggest that gallic acid derivatives could contribute to the development of safer therapies."

Journal • Oncology

Verastem Oncology announces submission of a Marketing Authorization application to the European Medicines Agency for Copiktra (duvelisib) (Verastem Press Release) - “Verastem, Inc….announced the submission of a Marketing Authorization Application to the European Medicines Agency (EMA) for COPIKTRA® (duvelisib), an oral inhibitor of phosphoinositide 3-kinase (PI3K), seeking approval for the treatment of patients with relapsed or refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and relapsed or refractory follicular lymphoma (FL).”

EMA filing • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology

Duvelisib and Venetoclax in Patients With Relapsed or Refractory Peripheral T-cell Lymphoma (PTCL) (clinicaltrials.gov) - P1/2 | N=12 | Not yet recruiting | Sponsor: Jonsson Comprehensive Cancer Center | Trial completion date: Mar 2031 ➔ Jun 2031 | Initiation date: Mar 2025 ➔ Jun 2025 | Trial primary completion date: Mar 2030 ➔ Jun 2030

Trial completion date • Trial initiation date • Trial primary completion date • Cutaneous T-cell Lymphoma • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Peripheral T-cell Lymphoma • Prolymphocytic Leukemia • T Cell Non-Hodgkin Lymphoma

TERZO: A Study of Duvelisib Versus Gemcitabine or Bendamustine in Participants With Relapsed/Refractory Nodal T Cell Lymphoma With T Follicular Helper (TFH) Phenotype (clinicaltrials.gov) - P3 | N=124 | Recruiting | Sponsor: SecuraBio | Not yet recruiting ➔ Recruiting

Enrollment open • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • T Cell Non-Hodgkin Lymphoma

FDA accepts New Drug Application for duvelisib and grants priority review (Verastem Press Release) - "Verastem...announced that the U.S. Food and Drug Administration (FDA) has accepted for filing with Priority Review its New Drug Application (NDA) for its lead product candidate duvelisib....Verastem is seeking full approval for the treatment of relapsed or refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and accelerated approval for the treatment of relapsed or refractory follicular lymphoma (FL). The FDA target action date is October 5, 2018."

NDA • PDUFA • Chronic Lymphocytic Leukemia • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Oncology

Management of Mycosis Fungoides and Sézary Syndrome With Oral Systemic Therapies. (PubMed, J Cutan Med Surg) - "FDA-approved oral therapies include bexarotene and vorinostat, both of which are effective in patients who are recalcitrant to prior topical therapies. Off-label oral therapies include methotrexate, acitretin, and chlorambucil...Chlorambucil is mainly used to treat erythrodermic MF. Investigational oral therapies for MF include tenalisib, duvelisib, cerdulatinib, lenalidomide, bortezomib, and azacytidine, and direct comparison studies between these investigational agents and FDA-approved therapies should be undertaken to better understand their role in the management of MF and SS."

Journal • Review • Cutaneous T-cell Lymphoma • Dermatology • Hematological Malignancies • Lymphoma • Mycosis Fungoides • Oncology • Sezary Syndrome • T Cell Non-Hodgkin Lymphoma

Duvelisib in Combination With BMS-986345 in Lymphoid Malignancy (clinicaltrials.gov) - P1 | N=14 | Completed | Sponsor: H. Lee Moffitt Cancer Center and Research Institute | Active, not recruiting ➔ Completed | Trial completion date: Jun 2025 ➔ Apr 2024

Trial completion • Trial completion date • B Cell Lymphoma • Hematological Malignancies • Hepatosplenic T-cell Lymphoma • Hodgkin Lymphoma • Leukemia • Lymphoma • Multiple Myeloma • Natural Killer/T-cell Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Primary Mediastinal Large B-Cell Lymphoma • ALK • BCL2 • BCL6 • CD8 • MYC • TNFRSF8

Targeting PI3K in Cancer Treatment: A Comprehensive Review with Insights from Clinical Outcomes. (PubMed, Eur J Pharmacol) - "Some PI3K inhibitors such as idelalisib, copanlisib, duvelisib, alpelisib, and umbralisib have received FDA-approval, and are effective in the treatment of breast cancer and haematologic malignancies. The resistance mechanisms provide barriers to the sustained efficacy of PI3K-targeted treatments. This study reviews recent advancements in PI3K inhibitors, covering their clinical status, mechanism of action, resistance mechanisms, and strategies to overcome resistance."

Clinical data • Journal • Review • Breast Cancer • Hematological Disorders • Hematological Malignancies • Oncology • Solid Tumor • PTEN

Duvelisib Plus Docetaxel In Recurrent/Metastatic HNSCC (clinicaltrials.gov) - P2 | N=26 | Active, not recruiting | Sponsor: Glenn J. Hanna | Trial completion date: Jan 2025 ➔ Jan 2026

Trial completion date • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • PD-L1

PRIMO: A Study of Duvelisib in Participants With Relapsed or Refractory Peripheral T-cell Lymphoma (PTCL) (clinicaltrials.gov) - P2 | N=156 | Completed | Sponsor: SecuraBio | N=103 ➔ 156

Enrollment change • Hematological Malignancies • Lymphoma • Natural Killer/T-cell Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Peripheral T-cell Lymphoma • T Cell Non-Hodgkin Lymphoma

Duvelisib and Nivolumab for the Treatment of Stage IIB-IVB Mycosis Fungoides and Sezary Syndrome (clinicaltrials.gov) - P1 | N=38 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | Trial completion date: Dec 2025 ➔ Nov 2027

Trial completion date • Cutaneous T-cell Lymphoma • Dermatology • Lymphoma • Mycosis Fungoides • Non-Hodgkin’s Lymphoma • Oncology • Sezary Syndrome

Combinatorial screen of targeted agents with the PI3K inhibitors inavolisib, alpelisib, duvelisib, and copanlisib in multi-cell type tumor spheroids. (PubMed, SLAS Discov) - "Additive and/or synergistic effects were observed with alpelisib or inavolisib or copanlisib in combination with a RAS/MEK/ERK pathway inhibitor, either selumetinib (MEK), ravoxertinib (ERK 1/2), or tovorafenib (DAY101, RAF). Combinations of each of these three PI3K inhibitors with the KRAS mutation specific inhibitors MTRX1133 (KRAS G12D) or sotorasib (KRAS G12C) had selective activity in cell lines harboring the corresponding target. Lastly, combination effects were observed from vertical inhibition of the PI3K/AKT/mTOR pathway with a PI3K inhibitor in combination with either the mTORC1/2 inhibitor sapanisertib or an AKT inhibitor, ipatasertib or afuresertib."

Journal • Oncology • KRAS