Secura Bio has initiated dosing in its Phase 3 TERZO study of COPIKTRA (duvelisib) for patients with relapsed or refractory nodal T-follicular helper cell lymphoma (nTFHL), marking the first Phase 3 investigation of a PI3K inhibitor in this rare cancer indication. The company announced that the first patient was dosed in June 2025, with interim data anticipated in early 2027.
Addressing an Unmet Medical Need
Nodal T-follicular helper cell lymphomas represent a group of aggressive non-Hodgkin lymphomas that originate from T-follicular helper cells and share common genetic, clinical, and cellular features. These lymphomas generally occur in people aged 60 and older and are slightly more common in males, typically presenting with widespread, enlarged, painless lymph nodes in the neck, armpit, and groin.
"Patients with relapsed or refractory nodal T-follicular helper cell lymphoma need meaningful treatment options, with the potential to extend and improve the quality of their lives," said Dr. Graham Collins, UK Site Investigator for the TERZO Study. "I am grateful to Secura Bio for continuing to evaluate COPIKTRA for diseases where the standard treatment protocol has been challenged by recurring relapses and mutations."
Currently, there are no well-established standards of care for patients with relapsed or refractory nTFHL, highlighting the significant unmet medical need in this patient population.
Trial Design and Endpoints
The Phase 3 TERZO study is a multicenter, open-label, randomized controlled trial comparing duvelisib versus investigator's choice of gemcitabine or bendamustine in patients with relapsed or refractory nTFHL. Patients in the European Union and United Kingdom will be randomized on a 1:1 basis and receive treatment until progressive disease or unacceptable toxicity occurs.
The study's primary endpoint is progression-free survival, while secondary endpoints include overall survival, objective response rate, complete response rate, duration of response, number of participants with adverse events, and quality of life. Secura Bio expects to enroll approximately 124 patients in the trial.
COPIKTRA's Mechanism and Current Indications
COPIKTRA is an oral inhibitor of phosphoinositide 3-kinase (PI3K) and represents the first US-approved dual inhibitor of PI3K-delta and PI3K-gamma pathways. These enzymes are known to support the growth and survival of malignant cells, with PI3K signaling potentially leading to malignant cell proliferation and playing a role in forming and maintaining a supportive tumor microenvironment.
The drug is currently indicated in the United States for treating adult patients with relapsed or refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) after at least two prior therapies. COPIKTRA is also being developed for peripheral T-cell lymphoma treatment, having received Fast Track status in the United States.
Building on Previous Research
"We are very pleased to have dosed our first patient in this Phase 3 study of COPIKTRA based on the results from our Phase 2 study in T-cell lymphomas – in particular the results from angioimmunoblastic T-cell lymphoma (AITL), a subtype of peripheral T-cell lymphoma (PTCL) that is strongly associated with the T follicular helper (TFH) cell phenotype," said Chip Romp, President and CEO of Secura Bio.
The company aims to develop COPIKTRA beyond its initial CLL/SLL indication as part of building a diverse oncology portfolio.
Safety Profile
COPIKTRA carries a boxed warning for fatal and serious toxicities, including infections (occurring in 31% of patients, with 4% fatal), diarrhea or colitis (18% incidence, <1% fatal), cutaneous reactions (5% incidence, <1% fatal), and pneumonitis (5% incidence, <1% fatal). The most common adverse reactions include diarrhea or colitis, neutropenia, rash, fatigue, pyrexia, cough, nausea, upper respiratory infection, pneumonia, musculoskeletal pain, and anemia.
