Duvelisib Induces Deep Responses in PTCL: Final Results of the Phase 2 PRIMO Trial of Duvelisib in Relapsed/Refractory Peripheral T-Cell Lymphoma

BACKGROUND: Peripheral T-cell lymphomas (PTCLs) are rare, heterogeneous, aggressive lymphomas. Five-year overall survival (OS) remains ∼30-40%, and most patients will develop relapsed or refractory (R/R) disease. Duvelisib is an oral dual inhibitor of phosphatidylinositol 3-kinase (PI3K)-δ and PI3K-γ isoforms. Here, we report on the final analysis of the phase 2 PRIMO trial (NCT03372057; Secura Bio, Inc.) evaluating duvelisib monotherapy in R/R PTCL. METHODS: PRIMO was conducted in 2 phases (Dose Optimization and Dose Expansion [PRIMO-EP]) at 45 centers globally. Eligible patients were ≥18 years of age, had histologically confirmed diagnosis of PTCL, and had received ≥2 cycles of 1 standard regimen for PTCL. Based on Dose Optimization results, the selected regimen for PRIMO-EP was 75 mg BID for 2 cycles (to maximize disease control) followed by 25 mg BID (to reduce late toxicities), continued until progressive disease or unacceptable toxicity. RESULTS: PRIMO-EP (N=123) outcomes included Independent Review Committee-assessed objective response rate (ORR): 48.0%, complete response rate (CRR): 33.3%, median progression-free survival (mPFS): 3.4 months, mOS: 12.4 months, median duration of response (mDOR): 7.9 months. In the AITL subgroup, outcomes were ORR: 62.2%, CRR: 51.4%, mPFS: 8.3 months, mOS: 18.1 months, mDOR: 11.3 months. Treatment-emergent adverse events (TEAEs) (any grade) occurred in 120 patients (97.6%), TEAEs grade ≥3 occurred in 91 patients (74.0%). TEAEs resulting in dose hold or dose reduction occurred in 44.7% and 9.8% of patients. CONCLUSIONS: The PRIMO study demonstrates significant activity and tolerability of duvelisib in patients with R/R PTCL, most notably in the AITL subgroup. This provides strong rationale for further development in PTCL, and more specifically in the subgroup of nodal T-follicular helper cell lymphoma.