Duvelisib in patients with relapsed/refractory peripheral T‐cell lymphoma from the phase 2 PRIMO Trial Expansion Phase: outcomes by baseline histology

Introduction: Peripheral T-cell lymphoma (PTCL) is a heterogeneous group of aggressive lymphomas with a poor prognosis for relapsed/refractory disease. The WHO classification of NK and T-cell lymphomas includes 39 entries; 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). Except for brentuximab vedotin in CD30-positive disease, agents were generally approved based on overall response rates (ORR) of less than 30%. The PRIMO Trial (NCT03372057; sponsored by Secura Bio, Inc.) evaluated 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 different PTCL subtypes. Here we present data on 3 specific subtypes of some of the patients (pts) included in the PRIMO trial (fully enrolled as of January 2022). Methods: Eligibility criteria included adults with pathologically confirmed PTCL after ≥2 cycles of at least 1 prior standard regimen. A criterion for CD4 lymphocyte count ≥50/mm3 was added for the Expansion Phase (EP). Based on dose optimization results, the EP dose was DUV 75 mg BID for 2 cycles, to maximize disease control, followed by 25 mg BID, to mitigate late toxicities, until progressive disease/unacceptable toxicity. Pneumocystis jirovecii prophylaxis was required; herpes simplex and varicella zoster virus prophylaxis were indicated as needed. The primary endpoint was ORR by IRC assessment (Lugano 2014 criteria); efficacy is or will be assessed in all pts who received ≥1 dose of DUV. Secondary objectives included additional outcome measures, safety, and pharmacokinetics. Exploratory endpoints included pharmacodynamics and biomarkers. Results: The PRIMO study included 101 pts from the EP (data cutoff October 1, 2021), with a median follow-up of 8.7 months (mo) from time of first response. In the overall PRIMO study (N = 101), pts had a median age of 67.0 (21–92) years, a median of 3 (1–9) prior lines of therapy, an ORR (by IRC) of 49%, a CR rate of 34%, and a median PFS of 3.6 mo. Pts with the 3 most common histology subtypes from the PRIMO study are included in the current analysis (n = 97); these are PTCL-NOS (n = 52), AITL (n = 30), and ALCL (n = 15). Median PFS stratified by baseline histology was 3.5 mo (PTCL-NOS), 9.1 mo (AITL), and 1.5 mo (ALCL). Table 1 shows additional outcomes by histology. Adverse events seen were consistent with those observed previously in the PRIMO trial with no additional unexpected treatment-related toxicities. Conclusions: The ORR (by IRC) of DUV was higher in pts 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 DUV may not be uniform across different types of lymphomas. Encore Abstract - previously submitted to EHA 2023 The research was funded by: Secura Bio, Inc. Keywords: molecular targeted therapies, ongoing trials Conflicts of interests pertinent to the abstract. N. Mehta-Shah Consultant or advisory role: AstraZeneca, Celgene/BMS, C4 Therapeutics, Celgene, Corvus, Daiichi Sankyo, Genentech/Roche, Innate Pharmaceuticals, Karyopharm, Kyowa Kirin, ONO Pharmaceuticals, Secura Bio, Verastem ​ E. D. Jacobsen Consultant or advisory role: Ascerta, Astra-Zeneca, Merck; Pharmacyclics, F. Hoffman-LaRoche, Novartis, Takeda P. L. Zinzani Consultant or advisory role: Celltrion, Gilead, Janssen-cilag, BMS, Servier, Sandoz, MSD, TG therapeutics, Takeda, Roche, Eusapharma, Kyowa Kirin, Novartis, ADC Therapeutics, Incyte, Beigene, Secura Bio​ J. Zain Consultant or advisory role: Kyowa Kirin, Mundi, Seattle Genetics​ G. Gritti Consultant or advisory role: Beigene, Clinigen, Genmab, Ideogen, Incyte, IQVIA, Italfarmaco, Kite-Gilead, Roche, Sandoz, Takeda K. Izutsu Consultant or advisory role: Celgene/BMS, MSD, AstraZeneca, AbbVie, Eisai, Incyte, Solasia, Novartis, Bayer, Pfizer, Janssen, Yakult, Kyowa Kirin, ONO Pharmaceuticals, Daiichi Sankyo, Chugai, Takeda, Beigene, Genmab, Otsuka, Loxo Oncology, FUJIFILM Toyamachemical, Symbio​ S. Waters Employment or leadership position: Secura Bio, Inc. J. E. Brammer Consultant or advisory role: BMS, Verastem Consultancy: Kymera, Seattle Genetics B. Pro Consultant or advisory role: Takeda, Seattle Genetics, Celgene, Verastem, Astex pharmaceuticals S. M. Horwitz Consultant or advisory role: ADC Therapeutics, Affimed, Celgene, Crispr Therapeutics, Daiichi Sankyo, Kyowa Hakko Kirin, Millennium /Takeda, Seattle Genetics, Verastem/SecuraBio, Acrotech Biopharma, C4 Therapeutics, Kyowa Hakko Kirin, Myeloid Therapeutics, ONO Pharmaceuticals, Seattle Genetics, SecuraBio, Shoreline Biosciences, Inc., Takeda, Trillium Therapeutics, Tubulis, Cimieo Therapeutics