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

Duvelisib in patients with relapsed/refractory peripheral T-cell lymphoma from the phase 2 PRIMO Trial Expansion Phase: outcomes by baseline histology (ICML 2023) - P2 | "Except for brentuximab vedotin in CD30-positive disease, agents were generally approved based on overall response rates (ORR) of less than 30%. The ORR (by IRC) of DUV was higher in pts with PTCL-NOS (48%) and AITL (67%), compared with ALCL (13%). This corresponded to a longer median PFS of 3.5 mo in PTCL-NOS and 9.1 mo in AITL compared with 1.5 mo in ALCL. Although not powered for subset analyses, this analysis suggests activity of DUV may not be uniform across different types of lymphomas."

Clinical • P2 data • Hematological Malignancies • Lymphoma • Oncology • Peripheral T-cell Lymphoma • T Cell Non-Hodgkin Lymphoma • CD4 • PIK3CG • TNFRSF8

A Phase 1 Trial of Duvelisib and Oral Azacitidine in Relapsed/Refractory T-Cell Lymphoma. (PubMed, Hematol Oncol) - P1 | "Randomized evaluation focused on the TFH subtype is warranted. TRIAL REGISTRATION: NCT05065866."

Journal • P1 data • Hematological Disorders • Hematological Malignancies • Lymphoma • Neutropenia • Oncology • Peripheral T-cell Lymphoma • T Cell Non-Hodgkin Lymphoma • Thrombocytopenia • Transplantation • PIK3CG

A phase I/II Study of Duvelisib plus Venetoclax in Patients with Relapsed/Refractory CLL/SLL or Richter Transformation. (PubMed, Blood Adv) - P1/2 | "Overall, duvelisib plus venetoclax was active in high-risk R/R CLL/SLL and RT, though serious adverse events occurred, including immune-mediated toxicities. NCT03534323."

Journal • P1/2 data • Chronic Lymphocytic Leukemia • Febrile Neutropenia • Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Richter's Syndrome • Small Lymphocytic Lymphoma • IGH • TP53

A Multicenter, Open-Label, Phase 3 Randomized Trial of Duvelisib Versus Investigator's Choice (Gemcitabine or Bendamustine) in Relapsed/Refractory Nodal T-Cell Lymphoma With T-Follicular Helper Phenotype (SOHO 2026) - P2, P3 | "Currently, the only agent approved in the EU/UK for R/R PTCL is brentuximab vedotin for anaplastic large-cell lymphoma. TERZO is the only phase 3 study dedicated to nTFHL in the EU/UK, designed to address this serious unmet need. ECOG: Eastern Cooperative Oncology Group, EU CT: EU Clinical Trials [Registry], EU/UK: European Union/United Kingdom, mPFS: median progression-free survival, NOS: not otherwise specified, ORR: objective response rate, OS: overall survival, PI3K: phosphatidylinositol 3-kinase, R/R: relapsed/refractory, SCT: stem cell transplant."

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

DUVELISIB IN PATIENTS WITH RELAPSED/REFRACTORY PERIPHERAL T-CELL LYMPHOMA FROM THE PHASE 2 PRIMO TRIAL EXPANSION PHASE: OUTCOMES BY BASELINE HISTOLOGY (EHA 2023) - P2 | "With the exception of brentuximab vedotin (BV) in CD30-positive disease, these agents were generally approved based on overall response rates (ORR) of less than 30%. The ORR (by IRC) of duvelisib was higher in patients with PTCL-NOS (48%) and AITL (67%), compared with ALCL (13%). This corresponded to a longer median PFS of 3.5 mo in PTCL-NOS and 9.1 mo in AITL compared with 1.5 mo in ALCL. Although not powered for subset analyses, this analysis suggests activity of duvelisib may not be uniform across different types of lymphomas."

Clinical • P2 data • Hematological Malignancies • Herpes Simplex • Herpes Zoster • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Peripheral T-cell Lymphoma • T Cell Non-Hodgkin Lymphoma • Varicella Zoster • CD4 • PIK3CG • TNFRSF8

High Rates of Remission with the Initial Treatment of Oral Azacitidine Plus CHOP for Peripheral T-Cell Lymphoma (PTCL): Clinical Outcomes and Biomarker Analysis of a Multi-Center Phase II Study (ASH 2021) - P2 | "This study demonstrates that priming with oral azacitidine (CC486) in combination with CHOP as initial therapy is safe, effective, and produces sustained remission in PTCL-TFH subtype. Epigenetic priming with azacitidine appears to inhibit the proliferation of TFH lymphoma cells, providing potential synergistic mechanism of action with chemotherapy. This active combination will be further evaluated in the upcoming ALLIANCE/ US Intergroup randomized study A051902, comparing oral azacitidine-CHO(E)P vs duvelisib-CHO(E)P against CHO(E)P in CD30 negative PTCL."

Biomarker • Clinical • Clinical data • P2 data • Anemia • Anorexia • Bone Marrow Transplantation • Cardiovascular • Fatigue • Febrile Neutropenia • Heart Failure • Hematological Malignancies • Immunology • Inflammation • Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Peripheral T-cell Lymphoma • T Cell Non-Hodgkin Lymphoma • Thrombocytopenia • Transplantation • DNMT3A • IDH2 • RHOA • TET2 • TNFRSF8 • TRB

Novel targeted therapies for central nervous system involvement in chronic lymphocytic leukemia: A systematic review. (PubMed, Ther Adv Hematol) - "Eligible studies reported adults with CNS involvement by CLL/SLL treated with targeted agents, including BTK inhibitors, venetoclax, duvelisib, dasatinib, or other novel therapies...Ibrutinib was the most frequently used agent, while venetoclax and ibrutinib-venetoclax showed favorable activity...However, the current evidence remains primarily exploratory and descriptive. Prospective multicenter studies are warranted to establish optimal treatment sequencing, combination strategies, and the role of adjunctive intrathecal therapy or radiotherapy."

IO biomarker • Journal • Review • B Cell Lymphoma • Chronic Lymphocytic Leukemia • CNS Disorders • Hematological Malignancies • Leukemia • Lymphoma • Oncology • Richter's Syndrome • Small Lymphocytic Lymphoma • IGH • TP53

Duvelisib plus romidepsin in relapsed/refractory T cell lymphomas: a phase 1b/2a trial. (PubMed, Nat Med) - P1 | "As reported here, we conducted a phase 1b/2a study of duvelisib in combination with either romidepsin (n = 66) or bortezomib (n = 32) in patients with relapsed/refractory TCL and found that the addition of romidepsin, but not bortezomib, appeared to increase efficacy while attenuating PI3K inhibitor-driven toxicity. These findings support further development of combined PI3K and histone deacetylase (HDAC) inhibition in TCLs and suggest a unique strategy to enable PI3K inhibitor-based combinations for additional patient populations. ClinicalTrials.gov identifier: NCT02783625 ."

Journal • P1/2 data • Fatigue • Hematological Disorders • Hematological Malignancies • Hepatology • Immunology • Lymphoma • Neutropenia • Oncology • Peripheral T-cell Lymphoma • T Cell Non-Hodgkin Lymphoma

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 | Suspended ➔ Recruiting

Enrollment open • 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

primary analysis of Phase ib trial of duvelisib for cytokine release syndrome prophylaxis in patients undergoing chimeric antigen receptor T cell therapy for non-hodgkins lymphoma (ASH 2025) - P1 | "Diagnoses included DLBCL (n = 20), MCL (6), FL (1) and PBMCL (1).Patients received axi-cel (22), liso-cel (14), brexu-cel (5) and tisa-cel (1).40 patients were evaluable for the primary endpoint. Duvelisib is also associated with delayed onset of CRS, which may enableoutpatient administration of CAR T-cells. Though limited by clinical heterogeneity, ORR and 1-year PFSare comparable to prior reports, suggesting duvelisib does not significantly inhibit CAR T-cell function"

CAR T-Cell Therapy • Clinical • Cytokine release syndrome • P1 data • Diffuse Large B Cell Lymphoma • Infectious Disease • Lymphoma • Non-Hodgkin’s Lymphoma • Septic Shock • CD8 • HEY1 • IL6

Duvelisib Maintenance for the Treatment of Peripheral T-Cell Lymphomas (clinicaltrials.gov) - P2 | N=25 | Recruiting | Sponsor: City of Hope Medical Center | Initiation date: Jun 2026 ➔ Oct 2026

Trial initiation date • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Peripheral T-cell Lymphoma • T Cell Non-Hodgkin Lymphoma • CD4

Sex-Specific Safety Profiles of PI3K Inhibitors: A Real-World Pharmacovigilance Study Based on FAERS Database. (PubMed, Clin Ther) - "This research identifies sex-specific AE patterns for PI3K inhibitors. Subsequent to FDR correction, significant PT level sex differences were detected for alpelisib, yet not for idelalisib. Moreover, no differences at the standard of care SOC level persisted for either drug. The findings regarding copanlisib and duvelisib remain indeterminate. These results provide clinically relevant signals for sex-tailored AE surveillance and necessitate prospective validation."

Adverse events • Journal • Real-world evidence • Diabetes

Stereoselective ecotoxicity and environmental stability of the anticancer drug duvelisib in aquatic systems. (PubMed, Environ Pollut) - "Screening-level QSAR predictions obtained with ECOSAR and VERA were broadly consistent with algal toxicity in terms of order of magnitude but were less suitable for bacterial bioluminescence inhibition and stereoselective interpretation. Overall, this study provides the first integrated assessment of duvelisib in aquatic systems and highlights the importance of stereochemistry and experimental validation in environmental hazard characterization of chiral anticancer drugs."

Journal • Oncology

A Study of Topical Duvelisib in Participants With Early-stage Mycosis Fungoides (clinicaltrials.gov) - P1 | N=30 | Not yet recruiting | Sponsor: SecuraBio

New P1 trial • Cutaneous T-cell Lymphoma • Dermatology • Hematological Malignancies • Lymphoma • Mycosis Fungoides • Non-Hodgkin’s Lymphoma • Oncology • T Cell Non-Hodgkin Lymphoma

Sustained remission for mycosis fungoides following duvelisib and mogamulizumab. (PubMed, JAAD Case Rep) - No abstract available

Journal • Cutaneous T-cell Lymphoma • Dermatology • Mycosis Fungoides • Oncology

Beyond Romidepsin: Novel Therapeutic Targets and Emerging Strategies for Relapsed and Refractory Peripheral T-Cell Lymphoma. (PubMed, Clin Lymphoma Myeloma Leuk) - "Following romidepsin's withdrawal from the R/R PTCL indication in 2021, the only FDA-approved agents are belinostat and pralatrexate, and Brentuximab Vedotin...EZH2 inhibitors represent a mechanistically novel class: valemetostat produced an ORR of 43.7% with a median duration of response of 11.9 months. JAK/STAT inhibitors, including golidocitinib (ORR 44.3%) and cerdulatinib (ORR 51.9% in AITL/TFH), show subtype-selective activity. Rational combinations yield superior efficacy: duvelisib plus romidepsin achieved ORR of 56% (CR 44%), while azacitidine combined with romidepsin produced ORR of 61% (CR 48%), particularly in TFH-phenotype disease (ORR 80%)...The Ro-CHOP trial's failure in unselected populations, contrasted with efficacy signals in nTFHL subsets, underscores a critical lesson: PTCL is not one disease, and future trial designs must incorporate biomarker-driven enrichment strategies to advance precision therapeutics. Improved outcomes can be expected..."

Journal • Review • Gene Therapies • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Peripheral T-cell Lymphoma • T Cell Non-Hodgkin Lymphoma • DNMT3A • KLRD1 • RHOA • TET2

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 2026) - P2, P3 | "Currently, the only agent approved in the EU/UK for treatment of R/R PTCL is brentuximab vedotin for anaplastic large-cell lymphoma. Novel agents such as romidepsin, belinostat, and pralatrexate have received accelerated approvals outside the EU/UK, but to date, none have received full approval...TERZO will test the hypothesis that DUV monotherapy is associated with improved outcomes versus GEM or BEN in patients with R/R nTFHL. TERZO is the only phase 3 study dedicated to nTFHL in the EU/UK, designed to address this serious unmet need."

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

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

Efficacy and tolerability of duvelisib in relapsed/refractory peripheral T-cell lymphoma: A multicenter real-world analysis. (ASCO 2026) - "118 patients received single agent duvelisib; 89 patients received duvelisib in combination with other agents (66 romidepsin, 12 bortezomib, 4 azacitadine, 3 ruxolitinib, 4 other). In this real world, multicenter analysis of patients with R/R PTCL treated with duvelisib-based regimens, the ORR of 51% was consistent with published trials. Duvelisib therapy was well tolerated and a minority required hospitalization for toxicity. This suggests that duvelisib is safe in patients with R/R PTCL who have poor prognosis and limited treatment options."

Clinical • Real-world • Real-world evidence • Adult T-Cell Leukemia-Lymphoma • Chronic Lymphocytic Leukemia • Gastroenterology • Gastrointestinal Disorder • Hematological Disorders • Hematological Malignancies • Immunology • Indolent Lymphoma • Leukemia • Lymphoma • Natural Killer/T-cell Lymphoma • Peripheral T-cell Lymphoma • T Cell Non-Hodgkin Lymphoma

Duvelisib Maintenance for the Treatment of Peripheral T-Cell Lymphomas (clinicaltrials.gov) - P2 | N=25 | Recruiting | Sponsor: City of Hope Medical Center | Not yet recruiting ➔ Recruiting

Enrollment open • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Peripheral T-cell Lymphoma • T Cell Non-Hodgkin Lymphoma • CD4

Prospective, Single Arm, Single Center Study of Duvelisib Combined With Chidamide in the Treatment of Newly Diagnosed Peripheral T-cell Lymphoma (PTCL) (clinicaltrials.gov) - P2 | N=36 | Recruiting | Sponsor: Liling Zhang | Trial completion date: Dec 2024 ➔ Dec 2026 | Trial primary completion date: Dec 2023 ➔ Oct 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

Identification of Novel Therapeutic Agent Candidates Through High Throughput Screening With Chemical Library Based on Molecular Subclassification in Canine Histiocytic Sarcoma Cell Lines. (PubMed, Vet Comp Oncol) - "Among the compounds examined, 73 compounds were identified as candidates to show antiproliferative effects in all CHS cell lines examined, and the median IC50 values of 5-fluorouracil and sunitinib were 7.49 μM and 608 nM, respectively, across all CHS cell lines. The amount of phosphorylated Akt protein decreased following duvelisib treatment in all eight CHS cell lines in Group A, but not in cell lines in Group B. Furthermore, duvelisib induced cell cycle arrest and increased cell death in a subset of Group A cell lines. These findings demonstrated that duvelisib exerted antiproliferative effects through inhibition of the Akt pathway in a subset of CHS cell lines while causing minimal cytotoxicity to normal cells."

Journal • Preclinical • Oncology • Sarcoma • Solid Tumor

Duvelisib Maintenance After Autologous Stem Cell Transplant in T-Cell Lymphomas (clinicaltrials.gov) - P2 | N=17 | Terminated | Sponsor: Washington University School of Medicine | Active, not recruiting ➔ Terminated; Loss of funding

Trial termination • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • T Cell Non-Hodgkin Lymphoma • Transplantation

Secura Bio Announces Journal of Clinical Oncology Publication of Final Results of Duvelisib PRIMO Phase 2 Trial in Relapsed/Refractory Peripheral T-cell Lymphoma (The Manila Times) - "The Journal of Clinical Oncology paper presents outcomes for 123 patients in the PRIMO-EP population. The trial demonstrated an overall response rate (ORR) of 48.0%, a complete response rate (CRR) of 33.3%, median progression-free survival (mPFS) of 3.4 months, and median overall survival (mOS) of 12.4 months. Currently available single agents have been observed to provide ORRs of less than 30% and CRRs below 15%....Based on these results, Secura Bio is conducting TERZO, a Phase 3 multicenter, open-label, randomized controlled clinical trial to evaluate duvelisib in R/R nodal T-follicular helper (TFH) cell lymphoma, in the European Union and the United Kingdom....Phase 3 TERZO trial now underway with greater than 50% enrollment achieved to date."

Enrollment status • P2 data • Nodal Peripheral T-cell Lymphoma • Peripheral T-cell Lymphoma

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

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