A Multicenter, Open-Label, Phase 3, Randomized Trial of Duvelisib vs Investigator's Choice in Relapsed/Refractory Nodal T-Cell Lymphoma With T-follicular Helper Phenotype
Peripheral T-cell lymphomas (PTCL) are rare, heterogeneous, aggressive non-Hodgkin lymphomas. Five-year overall survival remains approximately 30-40%, and most patients will develop relapsed/refractory (R/R) disease. The current World Health Organization classification groups angioimmunoblastic T-cell lymphoma (AITL), PTCL-not otherwise specified with T-follicular helper (TFH) phenotype, and follicular T-cell lymphoma under the category of nodal TFH lymphoma (nTFHL).
Treatment options for R/R nTFHL remain limited, and most patients will develop relapsed/refractory (R/R) disease. Duvelisib is an oral phosphatidylinositol 3-kinase-δ/γ inhibitor; its use in PTCL is investigational. In the phase 2 PRIMO study (NCT03372057) of duvelisib in R/R PTCL, objective response rate (ORR) was 48.0%, median progression-free survival (mPFS) was 3.4 months, and median overall survival (mOS) was 12.4 months. In patients with AITL, a subtype of nTFHL, outcomes were more pronounced: ORR 62.2%, mPFS 8.3 months, and mOS 18.1 months. These findings provided the rationale for TERZO™ (NCT06522737; EU CT: 2024-516605-23-00), an ongoing phase 3 study of duvelisib versus investigator's choice of gemcitabine or bendamustine (two standard of care regimens commonly used in R/R nTFHL) in adults with nTFHL.
Materials and Methods/Case Presentation/Objective:
Design and Methods: TERZO is a multicenter, open-label, randomized phase 3 study expected to enroll 124 adults at 45 sites in the EU/UK with R/R nTFHL who have progressed after at least 1 prior systemic anticancer therapy. Study duration is 48 months. Eligible patients must have measurable disease, Eastern Cooperative Oncology Group performance status ≤2, and no prior allogeneic stem cell transplant or phosphatidylinositol 3-kinase inhibitor therapy. Patients will be randomized 1:1 and stratified by the number of prior therapies and AITL score.
Arm 1 will receive duvelisib 75 mg orally twice daily for cycles 1 and 2, followed by duvelisib 25 mg twice daily for cycles ≥3 in 28-day cycles. Arm 2 will receive investigator's choice of gemcitabine 1200 mg/m2 intravenously on days 1, 8, and 15 of each 28-day cycle for up to 6 cycles or bendamustine 90-120 mg/m2 intravenously on days 1 and 2 of each 21-day cycle for up to 6 cycles.
The primary endpoint is independent review committee-assessed progression-free survival. Overall survival is a key secondary endpoint; additional secondary endpoints include investigator-assessed progression-free survival, ORR, complete response rate, duration of response, safety, quality of life, percentage of patients proceeding to stem cell transplant, investigator-assessed progression-free survival in patients proceeding to transplant, and pharmacokinetic parameters derived from blood concentrations of duvelisib and its metabolites.
Duvelisib monotherapy has demonstrated activity in R/R PTCL, with more pronounced effects in AITL. TERZO will test the hypothesis that duvelisib monotherapy is associated with improved outcomes versus gemcitabine or bendamustine 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.
Status: Recruiting
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