Portal de Periódicos da CAPES

P1172: DUVELISIB IN PATIENTS WITH RELAPSED/REFRACTORY PERIPHERAL T-CELL LYMPHOMA FROM THE PHASE 2 PRIMO TRIAL: UPDATED EXPANSION PHASE ANALYSIS

2022; Wolters Kluwer; Volume: 6; Linguagem: Inglês

10.1097/01.hs9.0000847552.42271.7c

2572-9241

P.‐L. Zinzani, Jasmine Zain, Monica Mead, Carla Casulo, E. D. Jacobsen, Giuseppe Gritti, Lauren Pinter‐Brown, K. Isutzu, D. Cohan, M. Daugherty, Jonathan E. Brammer, Neha Mehta‐Shah, Barbara Pro, Steven M. Horwitz,

Lymphoma Diagnosis and Treatment

Background: Peripheral T-cell lymphoma (PTCL) is a family of aggressive lymphomas, with a short median overall survival when relapsed or refractory (R/R). Current single-agent therapies for R/R PTCL have modest overall response rates (ORR) of <30%. Use of duvelisib (DUV), an oral dual inhibitor of phosphatidylinositol 3-kinase (PI3K)-δ and PI3K-γ isoforms, in PTCL is as an investigational agent only. Both Phase 1 data and prior interim analyses of this Phase 2, open-label, multi-center, parallel cohort PRIMO Trial (NCT03372057; supported by Secura Bio) demonstrated promising efficacy (ORR ~ 50%) of DUV in patients (pts) with R/R PTCL. Based on interim PRIMO data, DUV was added to the National Comprehensive Cancer Network® T-cell Lymphoma Guidelines® (Version 1.2022, 12/22/21) as a Category 2A other recommended regimen for pts with R/R PTCL of all subtypes. Here we present the latest PRIMO Expansion Phase (EP) data. Aims: The primary objective of the PRIMO EP is to determine the efficacy of DUV given at a recommended dose in pts with R/R PTCL; secondary objectives include additional efficacy measures, safety, and pharmacokinetics. Methods: EP eligibility criteria includes adults with pathologically confirmed PTCL, defined per WHO criteria, after ≥ 2 cycles of 1 prior standard regimen, and a CD4 lymphocyte count of ≥ 50/mm3. Based on the dose optimization results, the dose in the EP is DUV at 75 mg BID for 2 cycles, to maximize disease control, followed by 25 mg BID, to mitigate late toxicities, until progressive disease (PD) or unacceptable toxicity. Pneumocystis jirovecii prophylaxis is required; herpes simplex and varicella zoster virus prophylaxis are strongly recommended. The primary endpoint is ORR by IRC assessment using the Lugano 2014 criteria; efficacy is assessed in all pts that received at least 1 dose of DUV. Results: This updated analysis of the EP included 101 pts (data cutoff Oct 1, 2021); median 10.4 months follow-up from first dose. Pts had a median age of 67.0 years (range, 21-92) with a median of 3 prior lines of therapy (range 1-9). Fourteen pts remain on treatment with 87 pts withdrawn from treatment for: PD (44), clinical deterioration due to PD (4), adverse events (AE; 20), death (5), other (13), and withdrawal of consent (1). The ORR by IRC was 49% with a CR rate of 34%; responses were seen across multiple subtypes (Table 1 Median PFS was 3.6 months, though not yet fully mature. Five pts discontinued therapy to undergo stem cell transplantation. There were 3 treatment-related AEs associated with death (1 each): pneumonitis, Epstein-Barr associated lymphoproliferative disorder, and sepsis. AEs of special interest ≥ Grade 3 (all causality, number of events) were transaminase elevation increased (23), neutropenia (19), infections (10), cutaneous reactions (9), diarrhea (7), pneumonia (2), and pneumonitis (1). There was 1 event of colitis (Grade 1). ALT and/or AST elevations were the most common AEs leading to treatment discontinuations (15). Image:Summary/Conclusion: This updated analysis of 101 patients in the PRIMO EP demonstrated an ORR of 49% and a CR rate of 34%, which compares favorably to currently available single-agent options. Duvelisib was generally manageable with per-protocol dose modifications in this population, showing an AE profile consistent with what has been observed previously and no unexpected or novel toxicities. These data confirm duvelisib to be a promising agent for a disease set with high unmet needs, poor prognoses, and limited effective treatment options.