Duvelisib in Patients with Relapsed/Refractory Peripheral T-Cell Lymphoma from the Phase 2 Primo Trial: Results of an Interim Analysis
Authors: Brammer Jonathan E , Zinzani Pier Luigi , Zain Jasmine , Mead Monica , Casulo Carla , Jacobsen Eric D , Gritti Giuseppe , Litwak Debra , Cohan David , Katz Danica J , Mehta-Shah Neha , Pro Barbara , Horwitz Steven M. 
Published: November 2021

Abstract
Relapsed or refractory (R/R) peripheral T-cell lymphoma (PTCL) is a family of aggressive lymphomas, with a median overall survival (OS) of less than 6 months. Current FDA approved therapies for R/R PTCL have modest overall response rates (ORR) of &lt; 30%. Duvelisib (DUV), a dual PI3K-δ,γ inhibitor, is FDA approved at 25 mg twice daily (BID) for the treatment of R/R chronic lymphocytic leukemia and R/R follicular lymphoma. On 10/3/2019, DUV received orphan designation for treatment of patients with R/R T-cell lymphomas. In the Phase 2, open-label, multi-center, parallel cohort PRIMO trial of DUV in R/R PTCL, the initial results of the dose-optimization phase (N=33) demonstrated a 54% ORR in the 75 mg BID (N=13) and 35% in the 25 mg BID (N=20) cohorts, respectively, by investigator assessment (INV). (NCT03372057; supported by Secura Bio).
The expansion phase of PRIMO has a targeted enrollment of ~125 pts. Expansion phase eligibility criteria included histologically confirmed R/R PTCL after &gt;1 cycle of a prior standard regimen, a CD4 lymphocyte count of ≥ 50/mm 3 and required PJP prophylaxis. HSV/VZV prophylaxis was strongly recommended. Based on the dose optimization results, pts in the expansion phase receive DUV at 75 mg BID for 2 cycles to maximize rapid tumor control, followed by 25 mg BID to maintain long-term disease control and mitigate late toxicities, until progressive disease (PD) or unacceptable toxicity. The primary endpoint is ORR by IRC assessment, and secondary endpoints include ORR by INV assessment, duration of response (DOR), PFS, OS, disease control rate, and safety; all analyses consisted of pts that received at least 1 dose of DUV. This analysis is from an interim data cutoff as of May 21, 2021 that includes the first 6 months of data for the 78 patients included in the analysis.
Pts had a median age of 66.5 years (range, 21-92 years) and a median of 3 prior lines of therapy (range, 1-7). The ORR by IRC assessment was 50% (39/78 patients) and the CR rate was 32.1% (25/78 patients), see Table 1. 14 patients (18%) remained on treatment; 37 pts discontinued due to PD (47.4%), 15 discontinued to due adverse events (19.2%) , 4 died (5.1%), and 1 each discontinued for secondary malignancy, lack of response, and withdrawal of consent. 5 patients (6.4%) discontinued therapy to undergo stem cell transplant, which suggests that DUV may be used as a bridge to transplant for appropriate patients.
There were 3 deaths related or possibly related to duvelisib: pneumonitis, Epstein-Barr associated lymphoproliferative disorder, and sepsis. The most frequent &gt; Grade 3 adverse events seen were neutropenia (38.5%), ALT/AST increased (24.4%/ 21.8%), rash (7.7%), lymphocyte count decreased (7.7%), and sepsis (6.4%), see Table 2. ALT and/or AST elevations were the most common AEs leading to treatment discontinuations (N=12, 15.4%).
The interim results of the first 78 patients in the PRIMO expansion phase show an ORR of 50% and a CR rate of 32%, which suggests this therapy is superior to currently available SOC therapeutic options. Duvelisib was well tolerated in this population and remained consistent with the known safety profile of DUV. These data, from a large diverse population of T cell lymphoma patients, build upon prior reports demonstrating DUV as an active oral treatment for pts with RR PTCL. Data from this interim analysis may be updated prior to the abstract presentation.
Figure 1 Figure 1.

Disclosures
Brammer: Celgene: Research Funding; Kymera Therapeutics: Consultancy; Seattle Genetics: Speakers Bureau. Zinzani: BMS: Other: Advisory board, Speakers Bureau; ROCHE: Other, Speakers Bureau; SANDOZ: Other: Advisory board; ADC Therap.: Other; SERVIER: Other: Advisory board, Speakers Bureau; JANSSEN-CILAG: Other: Advisory board, Speakers Bureau; GILEAD: Other: Advisory board, Speakers Bureau; CELLTRION: Other: Advisory board, Speakers Bureau; EUSAPHARMA: Consultancy, Other, Speakers Bureau; TAKEDA: Other: Advisory board, Speakers Bureau; KYOWA KIRIN: Other, Speakers Bureau; NOVARTIS: Consultancy, Other, Speakers Bureau; TG Therapeutics: Other: Advisory board, Speakers Bureau; MSD: Consultancy, Other: Advisory board, Speakers Bureau; Incyte: Other, Speakers Bureau; Beigene: Other, Speakers Bureau; VERASTEM: Consultancy, Other: Advisory board, Speakers Bureau. Zain: Secura Bio, Ono , Legend, Kiyowa Kirin, Myeloid Therapeutics Verastem Daichi Sankyo: Consultancy; Secura Bio, DaichiSankyo, Abbvie: Research Funding; Kiyoaw Kirin, Secura Bio, Seattle Genetics: Honoraria. Casulo: BMS: Research Funding; Verastem: Research Funding; Genentech: Research Funding; Gilead: Research Funding. Jacobsen: Takeda: Consultancy; Syros: Consultancy; Janssen: Research Funding; Novartis: Research Funding; Pharmacyclics: Research Funding; Acerta: Research Funding. Gritti: Takeda: Consultancy; Roche: Consultancy; Kite Gilead: Consultancy; IQvia: Consultancy; Italfarmaco: Consultancy; Clinigen: Consultancy. Litwak: Secura Bio: Current Employment. Cohan: Secura Bio: Current Employment. Katz: Secura Bio: Current Employment. Mehta-Shah: C4 Therapeutics: Consultancy; Roche/Genentech: Research Funding; Kiowa Hakko Kirin: Consultancy; Karyopharm: Consultancy; Innate Pharmaceuticals: Research Funding; Celgene: Research Funding; Bristol Myers Squibb: Research Funding; AstraZeneca: Research Funding; Daiichi Sankyo: Consultancy, Research Funding; Secura Bio: Consultancy, Research Funding; Ono Pharmaceuticals: Consultancy; Corvus Pharmaceuticals: Research Funding; Verastem: Research Funding. Horwitz: ADC Therapeutics, Affimed, Aileron, Celgene, Daiichi Sankyo, Forty Seven, Inc., Kyowa Hakko Kirin, Millennium /Takeda, Seattle Genetics, Trillium Therapeutics, and Verastem/SecuraBio.: Consultancy, Research Funding; Affimed: Research Funding; Aileron: Research Funding; Acrotech Biopharma, Affimed, ADC Therapeutics, Astex, Merck, Portola Pharma, C4 Therapeutics, Celgene, Janssen, Kura Oncology, Kyowa Hakko Kirin, Myeloid Therapeutics, ONO Pharmaceuticals, Seattle Genetics, Shoreline Biosciences, Inc, Takeda, Trillium Th: Consultancy; Celgene: Research Funding; C4 Therapeutics: Consultancy; Crispr Therapeutics: Research Funding; Daiichi Sankyo: Research Funding; Forty Seven, Inc.: Research Funding; Kura Oncology: Consultancy; Kyowa Hakko Kirin: Consultancy, Research Funding; Millennium/Takeda: Research Funding; Myeloid Therapeutics: Consultancy; ONO Pharmaceuticals: Consultancy; Seattle Genetics: Consultancy, Research Funding; Secura Bio: Consultancy; Shoreline Biosciences, Inc.: Consultancy; Takeda: Consultancy; Trillium Therapeutics: Consultancy, Research Funding; Tubulis: Consultancy; Verastem/Securabio: Research Funding.

OffLabel Disclosure:
Duvelisib is approved in relapsed/refraction CLL/SLL and FL. This study evaluates duvelisib in PTCL