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

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

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

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: May 2025 ➔ Dec 2025 | Trial primary completion date: May 2025 ➔ Dec 2025

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

A051902: Testing the Addition of Duvelisib or CC-486 to the Usual Treatment for Peripheral T-Cell Lymphoma (clinicaltrials.gov) - P2 | N=170 | Recruiting | Sponsor: Alliance for Clinical Trials in Oncology | Trial completion date: Jan 2026 ➔ Jun 2026 | Trial primary completion date: Jun 2025 ➔ Jun 2026

Trial completion date • Trial primary completion date • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Peripheral T-cell Lymphoma • T Cell Non-Hodgkin Lymphoma • BCL6 • CXCL13 • ICOS • MME • PD-1 • TNFRSF8

A Study of Ruxolitinib and Duvelisib in People With Lymphoma (clinicaltrials.gov) - P1 | N=70 | Recruiting | Sponsor: Memorial Sloan Kettering Cancer Center | Active, not recruiting ➔ Recruiting | N=49 ➔ 70 | Trial completion date: Aug 2025 ➔ Aug 2026 | Trial primary completion date: Aug 2025 ➔ Aug 2026

Enrollment change • Enrollment open • 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 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) | Recruiting ➔ Active, not recruiting

Enrollment closed • Cutaneous T-cell Lymphoma • Dermatology • Lymphoma • Mycosis Fungoides • Non-Hodgkin’s Lymphoma • Oncology • Sezary Syndrome

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

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

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

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

Duvelisib is a novel NFAT inhibitor that mitigates adalimumab-induced immunogenicity. (PubMed, Front Pharmacol) - "Although methotrexate (MTX) can mitigate TNFi immunogenicity, its adverse effects necessitate alternative strategies. DV is a promising NFAT inhibitor that can protect against TNFi immunogenicity without inhibiting calcineurin phosphatase activity. Our results suggest that the future development of DV analogs may be of interest as agents to attenuate unwanted immune responses."

Journal • Immunology • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology • CD4 • NFATC1

Mechanism of CRS: Critical Roles of IFN-γ, CD40L, and CD4 Cells. (TCT-ASTCT-CIBMTR 2025) - P1, P2 | "These observations led to two clinical trials testing itacitinib (NCT04071366) and duvelisib (NCT05044039) as CRS prophylaxis after CART19 infusion. Further, Lentiviral overexpression of CD40L in CD8 CART19 resulted in robust surface expression and secretion of CD40L as well as dramatic production of IL-6 by iDC (Data not shown). Together, our studies clearly implicate two major pathways that are necessary and sufficient for CRS: 1) IFN-γ/IFN-γR/JAK1/2 axis (both CD4 and CD8) and 2) CD40L/CD40 PI3Kg/d axis (exclusively CD4) and represent logical targets for future CRS mitigation strategies in vivo ."

IO biomarker • Hematological Disorders • Hematological Malignancies • Oncology • CD40LG • CD8 • CSF2 • GLI2 • IFNG • IL4 • IL6 • JAK1

Duvelisib Exposure to Enhance Immune Profiles of T Cells in Patients With Recurrent or Refractory Diffuse Large B-Cell Lymphoma, DEEP T CELLS Study (clinicaltrials.gov) - P1 | N=4 | Completed | Sponsor: Emory University | Recruiting ➔ Completed | N=20 ➔ 4 | Trial completion date: Aug 2025 ➔ Sep 2024 | Trial primary completion date: Aug 2024 ➔ Mar 2024

Enrollment change • Trial completion • Trial completion date • Trial primary completion date • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD27

Targeting TTK Inhibits Tumorigenesis of T-Cell Lymphoma Through Dephosphorylating p38α and Activating AMPK/mTOR Pathway. (PubMed, Adv Sci (Weinh)) - "CFI-402257, a specific inhibitor of TTK, is found to exhibit anti-tumor effects and exerted synergistic efficacy with PI3K inhibitor, Duvelisib, in TCL. The study shows that TTK contributes to the development of TCL by regulating p38α-mediated AMPK/mTOR pathway. CFI-402257 is expected to be a promising strategy for TCL treatment."

Journal • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • T Cell Non-Hodgkin Lymphoma • Targeted Protein Degradation • TTK

Intermittent Duvelisib Dosing in Treating Patients With Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma (clinicaltrials.gov) - P2 | N=15 | Active, not recruiting | Sponsor: City of Hope Medical Center | Trial completion date: Dec 2024 ➔ Jun 2025

Trial completion date • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Small Lymphocytic Lymphoma • BCL2 • CCND1 • FCER2

Duvelisib Plus Venetoclax Is Active in Relapsed/Refractory CLL and Richter Syndrome (OncLive) - P1/2 | N=67 | NCT03534323 | "Duvelisib (Copiktra) plus venetoclax (Venclexta) was shown to be active in relapsed/refractory chronic lymphocytic leukemia (CLL) and Richter syndrome (RS), including in patients with high-risk, TP53-aberrant disease and those who had received prior treatment with BTK inhibitors, according to data from the phase 2 portion of a phase 1/2 trial (NCT03534323) that were presented at the 2024 ASH Annual Meeting. The complete remission (CR) and CR with incomplete count recovery (CRi) rates were 62% in patients with CLL or small lymphocytic lymphoma (SLL; n = 29). After cycle 12, the CR/CRi rate was 44% in this population. The CR/CRi rate in the TP53-aberrant patient subgroup (n = 14) was 64%; in patients with TP53-aberrant disease who had received prior BTK inhibition (n = 13), this rate was 46%."

P2 data • Chronic Lymphocytic Leukemia • Richter's Syndrome • Small Lymphocytic Lymphoma