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. 2023 Aug 18:63:102130.
doi: 10.1016/j.eclinm.2023.102130. eCollection 2023 Sep.

Parsaclisib, a PI3Kδ inhibitor, in relapsed and refractory follicular lymphoma (CITADEL-203): a phase 2 study

Marek Trněný  1 , Abraham Avigdor  2   3 , Matthew S McKinney  4 , Shankara Paneesha  5 , Björn E Wahlin  6 , John S Hrom  7 , David Cunningham  8 , Nicholas Morley  9 , Miguel Canales  10 , Mariana Bastos-Oreiro  11 , David Belada  12 , Liliana Devizzi  13 , Fred Zheng  14 , Douglas J DeMarini  14 , Wei Jiang  14 , Ping Jiang  14 , Ryan C Lynch  15
Affiliations

Parsaclisib, a PI3Kδ inhibitor, in relapsed and refractory follicular lymphoma (CITADEL-203): a phase 2 study

Marek Trněný et al. EClinicalMedicine. .

Abstract

Background: Parsaclisib, a potent and highly selective PI3Kδ inhibitor, has shown clinical benefit in patients with relapsed or refractory (R/R) B-cell malignancies. This phase 2 study (CITADEL-203; NCT03126019, EudraCT 2017-001624-22) assessed efficacy and safety of parsaclisib monotherapy in patients with R/R follicular lymphoma (FL).

Methods: Patients ≥18 years of age with histologically confirmed R/R FL (grade 1-3a) and prior treatment with ≥2 systemic therapies received parsaclisib 20 mg once daily (QD) for 8 weeks then parsaclisib 20 mg once weekly (weekly dosing group [WG]) or parsaclisib 20 mg QD for 8 weeks then parsaclisib 2.5 mg QD (daily dosing group [DG]); DG was selected for further assessment. Primary endpoint was objective response rate (ORR).

Findings: At data cut-off (January 15, 2021), 126 patients had been treated (WG: n = 23; DG: n = 103). ORR (95% confidence interval [CI]) was 77.7% (68.4-85.3) with a complete response rate (95% CI) of 19.4% (12.3-28.4) in DG; median (95% CI) duration of response was 14.7 months (10.4-not estimable [NE]), median progression-free survival was 15.8 months (11.0-NE), and median overall survival was not reached. The most common any-grade treatment-emergent adverse events (TEAEs) among all treated patients included diarrhoea (n = 48, 38.1%), nausea (n = 31, 24.6%), and cough (n = 28, 22.2%); the most common grade ≥3 TEAEs were diarrhoea (n = 15, 11.9%), neutropenia (n = 13, 10.3%), and colitis (n = 7, 5.6%). Dose interruption, reduction, and discontinuation from TEAEs occurred in 46.8% (n = 59), 17.5% (n = 22), and 23.8% (n = 30) of patients, respectively.

Interpretation: Treatment with parsaclisib demonstrated rapid and durable responses, and a manageable safety profile in patients with R/R FL.

Funding: Incyte Corporation.

Keywords: Follicular lymphoma; Non-Hodgkin lymphoma; PI3K inhibitor; Parsaclisib.

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Conflict of interest statement

Marek Trněný—Consultancy: AbbVie, Amgen, Bristol Myers Squibb, Celgene, Gilead Sciences, Incyte Corporation, Janssen, MorphoSys, Roche, and Takeda. Honoraria: AbbVie, Amgen, Bristol Myers Squibb, Gilead Sciences, Incyte Corporation, Janssen, MorphoSys, Roche, and Takeda. Travel, accommodations, or expenses: AbbVie, Bristol Myers Squibb, Gilead Sciences, Janssen, Roche, and Takeda. Research funding: Roche. Abraham Avigdor—Consultancy: Gilead Sciences, Pfizer, and Takeda. Honoraria: Gilead Sciences, Pfizer, and Takeda. Research funding: Bristol Myers Squibb and Janssen. Matthew S. McKinney—Consultancy: BTG Specialty Pharmaceuticals, Celgene, Genentech, Molecular Templates, Pharmacyclics, and Verastem Oncology. Honoraria: Genentech and Kite Pharma/Gilead Sciences. Research funding: BeiGene, Celgene, Genentech, Incyte Corporation, Molecular Templates, Nordic Nanovector, and Novartis. Speakers bureau: Kite Pharma/Gilead Sciences. Shankara Paneesha—Honoraria: AbbVie, Bristol Myers Squibb, Celgene, Gilead Sciences, and Janssen. Björn E. Wahlin—Consultancy: Roche. Research funding: Gilead Sciences and Roche. David Cunningham—Advisory committee: OVIBIO. Research funding: 4SC, Amgen, AstraZeneca, Bayer, Celgene, Clovis Oncology, Eli Lilly & Company, Janssen, MedImmune, Merck, Merrimack Pharmaceuticals, and Sanofi. Nicholas Morley—Advisory board: Roche. Honoraria: Kite Pharma and Janssen. Conference support: AbbVie, Roche, and Takeda. Miguel Canales—Honoraria: BeiGene, Celgene, Gilead Sciences, Incyte Corporation, Janssen, Karyopharm, Kyowa, Novartis, Sandoz, and Takeda. Speakers' bureau: Amgen, Janssen, Kyowa, Roche, Sandoz, and Takeda. Mariana Bastos-Oreiro—Honoraria: Bristol Myers Squibb/Celgene, Gilead Sciences, Janssen, Novartis, and Roche. Research funding: Roche. Speakers’ bureau: Bristol Myers Squibb/Celgene, Janssen, Kite Pharma, Roche, Novartis, and Takeda. David Belada—Consultancy: Gilead Sciences, Janssen, Roche, and Takeda. Board of Directors or Advisory committee: Gilead Sciences, Janssen, Roche, and Takeda. Travel expenses: Gilead Sciences, Roche, and Takeda. Research funding: Celgene, Gilead Sciences, Janssen, Roche, and Takeda. Fred Zheng—Employment and stock ownership: Incyte Corporation. Douglas J. DeMarini—Former employment and stock ownership: Incyte Corporation. Wei Jiang—Former employment and stock ownership: Incyte Corporation. Ping Jiang—Former employment and stock ownership: Incyte Corporation. Ryan C. Lynch—Consultancy: MorphoSys. Research funding: Bayer, Cyteir Therapeutics, Genentech, Incyte Corporation, Juno Pharmaceuticals, Rhizen Pharmaceuticals, Takeda, and TG Therapeutics. John S. Hrom and Liliana Devizzi—No relevant financial relationships to disclose.

Figures

Fig. 1
Fig. 1
CITADEL-203 patient disposition. QD = once-daily. QW = once-weekly. ∗Patients were allocated using a randomisation schedule to one of the parsaclisib dosing schedules, but this was not a randomised trial and no statistical comparisons were planned between treatment groups. †Includes 11 patients who switched to 2.5 mg once-daily parsaclisib after starting the 20 mg once-weekly period.
Fig. 2
Fig. 2
Best percentage change from baseline in target lesion size by independent review committee.
Fig. 3
Fig. 3
(A) Cumulative time to response curves, and (B) Kaplan–Meier estimates of duration of response (DOR) and (C) progression-free survival (PFS) by independent review committee, and (D) overall survival (OS) in the daily dosing group (blue) and all treated patients (green).
See this image and copyright information in PMC

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