Duvelisib Shows Promising Results in Relapsed/Refractory Peripheral T-Cell Lymphoma Phase 2 Trial
核心洞察
Duvelisib demonstrated a 48.0% overall response rate and 33.3% complete response rate in heavily pretreated peripheral T-cell lymphoma (搜索) patients, significantly exceeding current single-agent therapies.
The angioimmunoblastic T-cell lymphoma (搜索) subgroup showed particularly strong outcomes with 62.2% overall response rate and 8.3 months median progression-free survival.
Secura Bio (搜索)'s Phase 3 TERZO trial evaluating duvelisib in nodal T-follicular helper cell lymphoma has achieved over 50% enrollment based on these encouraging results.
Secura Bio (搜索) announced the publication of final Phase 2 PRIMO trial results in the Journal of Clinical Oncology, demonstrating that duvelisib, an oral dual PI3K-delta (搜索) and PI3K-gamma (搜索) inhibitor, achieved clinically meaningful response rates in patients with relapsed or refractory peripheral T-cell lymphoma (搜索) (R/R PTCL). The results show promise for addressing a significant unmet medical need in this aggressive cancer type.
Strong Efficacy Signals in Heavily Pretreated Population
The global, open-label, single-arm PRIMO trial enrolled 123 adult patients with R/R PTCL across the United States, European Union, United Kingdom, and Japan. Patients were heavily pretreated with a median of two prior anticancer therapies, ranging from one to nine previous treatments.
The trial demonstrated an overall response rate (ORR) of 48.0% and a complete response rate (CRR) of 33.3%, with median progression-free survival of 3.4 months and median overall survival of 12.4 months. These results compare favorably to currently available single agents, which have been observed to provide ORRs of less than 30% and CRRs below 15%.
"PTCL is a rare, aggressive type of non-Hodgkin lymphoma (搜索), and relapsed and refractory PTCL is an area of tremendous unmet need," said Dr. Neha Mehta-Shah, Associate Professor of Medicine at Washington University in St. Louis and one of the study's lead authors. "Currently, there are only limited treatments, and the treatments we have are effective for just a minority of patients and lack durability."
Exceptional Activity in AITL Subgroup
The trial revealed particularly encouraging results in the angioimmunoblastic T-cell lymphoma (搜索) (AITL) subgroup, which achieved the highest response rates by baseline histology. The AITL subgroup demonstrated an ORR of 62.2%, compared to 49.1% in PTCL-NOS and 15.0% in ALCL subgroups.
More notably, the AITL subgroup showed superior outcomes across multiple efficacy measures compared to the overall population: complete response rate of 51.4% versus 33.3%, median progression-free survival of 8.3 months versus 3.4 months, and overall survival of 18.1 months versus 12.4 months.
"The PRIMO data in AITL are especially promising because they provide a compelling biological rationale for duvelisib in TFH-derived lymphomas," said Dr. Christiane Langer, Senior Vice President, Head of Clinical and Medical Affairs at Secura Bio (搜索).
Manageable Safety Profile
Duvelisib was administered at 75 mg twice daily for two 28-day cycles, followed by 25 mg twice daily until disease progression or unacceptable toxicity. The safety profile was consistent with previous interim analyses, with adverse events generally manageable through per-protocol dose modifications.
The most frequently occurring treatment-emergent adverse events in ≥15% of patients included alanine aminotransferase increased (37.4%), aspartate aminotransferase increased (35.8%), neutrophil count decreased (33.3%), diarrhea (33.3%), platelet count decreased (26.0%), and fatigue (26.0%).
Bridge to Transplant Potential
The study provided encouraging data on transplant outcomes, with 19 patients proceeding to stem cell transplant at treatment discontinuation. The estimated 4-year overall survival in this cohort was 75%, supporting duvelisib's potential role as an effective bridge to transplant.
"For some patients, duvelisib may allow reconsideration of stem cell transplant by achieving disease control quickly enough to make this a realistic next step in their treatment journey," noted Dr. Langer.
Phase 3 Trial Underway
Based on the PRIMO results, particularly the strong activity in the AITL subgroup, Secura Bio (搜索) is conducting the Phase 3 TERZO trial. This multicenter, open-label, randomized controlled study is evaluating duvelisib in relapsed/refractory nodal T-follicular helper cell lymphoma in the European Union and United Kingdom, with enrollment already surpassing 50%.
The PRIMO data have already supported duvelisib's listing as a preferred treatment option for R/R PTCL within National Comprehensive Cancer Network guidelines. Additionally, duvelisib is being investigated in combination with CHOP for untreated PTCL patients in an ongoing US intergroup trial.
PTCL represents a rare but aggressive form of non-Hodgkin lymphoma (搜索), accounting for 10-15% of all cases and primarily affecting patients aged 60 years and older. Currently, no well-established standards of care exist for patients with relapsed or refractory disease, highlighting the clinical significance of these duvelisib results.