P1124: DUVELISIB IN PATIENTS WITH RELAPSED/REFRACTORY PERIPHERAL T-CELL LYMPHOMA FROM THE PHASE 2 PRIMO TRIAL EXPANSION PHASE: OUTCOMES BY BASELINE HISTOLOGY

Topic: 19. Aggressive Non-Hodgkin lymphoma - Clinical Background: Peripheral T-cell lymphoma (PTCL) is a heterogeneous group of aggressive lymphomas, with a poor prognosis and a shortened survival for relapsed or refractory (R/R) disease. In the 5th edition of the World Health Organization (WHO) classification of NK and T-cell lymphomas, there are 39 entries, of which the 3 most common subtypes in the US are PTCL-NOS (not otherwise specified), angioimmunoblastic T-cell lymphoma (AITL), and anaplastic large-cell lymphoma (ALCL). With the exception of brentuximab vedotin (BV) in CD30-positive disease, these agents were generally approved based on overall response rates (ORR) of less than 30%. The PRIMO Trial (NCT03372057; sponsored by Secura Bio, Inc.) evaluates duvelisib (DUV), an oral dual inhibitor of phosphatidylinositol 3-kinase (PI3K)-δ and PI3K-γ isoforms, in PTCL. Anti-tumor activity of single agents may not be uniform across the different subtypes of PTCL. Here we present data on the 3 specific subtypes by histology of some of the patients included in the PRIMO trial, which is fully enrolled as of January 2022. Aims: The primary objective of the PRIMO Trial Expansion Phase was to determine the efficacy of duvelisib at an optimal dose in patients with R/R PTCL; secondary objectives included additional outcome measures, tolerability and safety, and pharmacokinetics. Exploratory endpoints included pharmacodynamics and biomarkers. Methods: Eligibility criteria included adult individuals with pathologically confirmed PTCL (defined per the 2016 revision of the WHO classification of lymphoid neoplasms), after ≥2 cycles of at least 1 prior standard regimen. A criterion for a CD4 lymphocyte count of ≥50/mm3 was added for the Expansion Phase. Based on dose optimization results, the protocol dose in the Expansion Phase was DUV 75 mg BID for 2 cycles, to maximize disease control, followed by 25 mg BID, to mitigate late toxicities, until progressive disease or unacceptable toxicity. Pneumocystis jirovecii prophylaxis was required; herpes simplex and varicella zoster virus prophylaxis were also indicated as needed. The primary endpoint was ORR by Independent Review Committee (IRC) assessment using Lugano 2014 criteria; efficacy is or will be assessed in all patients that received ≥1 dose of DUV. Results: The PRIMO study included 101 patients from the Expansion Phase (data cutoff Oct 1, 2021), with a median follow-up of 8.7 months (mo) from time of first response. In the overall PRIMO study (N=101), patients had a median age of 67 years (range, 21-92), with a median of 3 prior lines of therapy (range 1-9). The overall population (N=101) had an ORR (by IRC) of 49%, a complete response rate of 34%, and a median PFS of 3.6 mo. Patients with the 3 most common baseline histology subtypes from the PRIMO study are included in the current analysis (n=97); these are PTCL (n=52), AITL (n=30), and ALCL (n=15). The median progression-free survival (PFS) stratified by baseline histology was 3.5 mo for PTCL-NOS, 9.1 mo for AITL, and 1.5 mo for ALCL. Additional outcomes stratified by baseline histology are shown in Table 1. The types of adverse events seen were consistent with those observed previously in the PRIMO trial with no additional unexpected treatment-related toxicities. Summary/Conclusion: The ORR (by IRC) of duvelisib was higher in patients with PTCL-NOS (48%) and AITL (67%), compared with ALCL (13%). This corresponded to a longer median PFS of 3.5 mo in PTCL-NOS and 9.1 mo in AITL compared with 1.5 mo in ALCL. Although not powered for subset analyses, this analysis suggests activity of duvelisib may not be uniform across different types of lymphomas.Keywords: Non-Hodgkin’s lymphoma, PI3 kinase, Peripheral T-cell lymphoma