{"doi":"10.1002/hon.70096_855","title":"855 | A PHASE 3 RANDOMIZED TRIAL: DUVELISIB VERSUS INVESTIGATOR CHOICE (GEMCITABINE OR BENDAMUSTINE) IN RELAPSED/REFRACTORY NODAL T‐CELL LYMPHOMA WITH T‐FOLLICULAR HELPER PHENOTYPE","abstract":"E. Domingo-Domenech, D. Sidransky, O. Bentur, and P. Zinzani equally contributing author. 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. Due to similarities in clinical, immunophenotypic and genetic characteristics, the 5th edition of the WHO classification of lymphoid neoplasms groups AITL, PTCL-NOS with TFH phenotype, and follicular T-cell lymphoma under the category nodal T-follicular helper cell lymphoma (nTFHL). Duvelisib is an oral inhibitor of phosphatidylinositol 3-kinase-δ and -γ. US indications: adults with R/R chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) after ≥ 2 prior lines of systemic therapy. US Limitations of Use: Duvelisib is not indicated or recommended for the treatment of any patients with CLL/SLL as initial or second line treatment due to increased risk of treatment-related mortality. EU/UK indications: adults with R/R CLL after ≥ 2 prior therapies and for follicular lymphoma that is refractory to ≥ 2 prior systemic therapies. The use of duvelisib in PTCL is investigational. In the PRIMO study (NCT03372057), outcomes with DUV in R/R PTCL were objective response rate (ORR) 48.0%, median progression-free survival (mPFS) 3.45 mo, and median overall survival (mOS) 12.35 mo. In patients with AITL, outcomes were ORR 62.2%, mPFS 8.34 mo, and mOS 18.07 mo. The TERZO study (NCT06522737; EU CT: 2024-516605-23-00) will evaluate DUV versus investigator (INV) choice of gemcitabine (GEM) or bendamustine (BEN), two standard of care regimens commonly used in clinical practice in patients with R/R nTFHL. TERZO is a multicenter, open-label, phase 3, randomized study expected to enroll 124 patients (∼45 EU/UK sites) with R/R nTFHL who have progressed on ≥ 1 line of systemic anticancer therapy. Patients will be randomized 1:1 and stratified by number of prior therapies and AITL score. Arm 1: DUV 75 mg orally twice daily (BID) for cycles 1 and 2, and DUV 25 mg BID for cycles 3+, in 28-day cycles. Arm 2: either GEM 1200 mg/m2 IV on Day (D) 1, 8, and 15 of each 28-day cycle (up to 6 cycles) or BEN 90–120 mg/m2 IV on D1 and 2 of each 21-day cycle (up to 6 cycles). Primary endpoint: Independent Review Committee-assessed PFS; key secondary endpoint: OS; additional secondary endpoints: INV-assessed PFS, ORR, complete response rate, duration of response, safety, quality-of-life, % patients proceeding to stem cell transplant (SCT), and INV-assessed PFS in patients with SCT; exploratory endpoints: AITL versus non-AITL outcomes, whole exome sequencing, circulating DNA, AITL score. Eligibility criteria include adults with R/R nTFHL, ≥ 1 prior line of systemic therapy, measurable disease, ECOG performance status ≤ 2, and no prior history of allogeneic SCT or PI3K inhibitor use. 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. Research funding declaration: This study was sponsored and supported by Secura Bio, Inc. Encore Abstract: EHA 2025; Regional or national meetings with up to 1000 attendees Keywords: aggressive T-cell non-Hodgkin lymphoma; ongoing trials Potential sources of conflict of interest: K. Cwynarski Consultant or advisory role: Roche, Gilead, KITE, Incyte, Abbvie, BMS, Secura Bio, Autolus, Sobi, Acrotech Educational grants: Roche, KITE, BMS D. Sidransky Consultant or advisory role: Secura Bio, Inc. O. Bentur Employment or leadership position: Secura Bio, Inc. P. Zinzani Consultant or advisory role: Secura Bio, Inc., Celltrion, Gilead, Janssen-Cilag, BMS, Servier, Sandoz, MSD, Astrazeneca, Takeda, Roche, Eusapharma, Kyowa Kirin, Novartis, ADC, Incyte, Beigene","journal":"Hematological Oncology","year":2025,"id":568490,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9598,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":882194,"name":"Eva Domingo‐Doménech","orcid":"0000-0001-8907-090X","position":1,"is_corresponding":false},{"id":24648,"name":"David Sidransky","orcid":null,"position":2,"is_corresponding":false},{"id":775929,"name":"Ohad S. Bentur","orcid":"0000-0002-5976-7121","position":3,"is_corresponding":false},{"id":488588,"name":"Pier Luigi Zinzani","orcid":"0000-0002-2112-2651","position":4,"is_corresponding":false},{"id":1472733,"name":"Kate Cwynarski","orcid":"0000-0001-9936-3431","position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-19T02:56:52.212268Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}