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382 Efficacy and Safety of Parsaclisib in Patients with Relapsed or Refractory Mantle Cell Lymphoma Not Previously Treated with a BTK Inhibitor: Primary Analysis from a Phase 2 Study (CITADEL-205)

Program: Oral and Poster Abstracts
Type: Oral
Session: 623. Mantle Cell, Follicular, and Other B-Cell Lymphomas: Clinical and Epidemiological: Front-line Induction Therapy and Novel Agents After Relapse
Hematology Disease Topics & Pathways:
Clinical Trials, Adults, Lymphomas, Non-Hodgkin Lymphoma, Non-Biological, Clinical Research, B Cell Lymphoma, Diseases, Aggressive Lymphoma, Therapies, Lymphoid Malignancies, Study Population
Sunday, December 12, 2021: 10:15 AM

Amitkumar Mehta, MD1, Marek Trněný, MD2, Jan Walewski, MD, PhD3, Vincent Ribrag, MD4, Caroline Dartigeas, MD5*, Jacob Haaber Christensen, MD, PhD6*, Fabrizio Pane, MD7, Guillermo Rodriguez, MD8*, Michal Taszner, MD9*, Parameswaran Venugopal, MD10, Vittorio Ruggero Zilioli, MD11*, Fred Zheng, MD12*, Douglas J DeMarini, PhD12*, Wei Jiang, PhD12* and Pier Luigi Zinzani, MD13

1UAB School of Medicine, Birmingham, AL
2Charles University, General Hospital, Prague, Czech Republic
3Department of Lymphoid Malignancies, Maria Sklodowska-Curie National Research Institute of Oncology, Warszawa, Poland
4Institut Gustave Roussy, Villejuif, France
5CHRU Tours, Tours, France
6University of Southern Denmark, Odense, Denmark
7University of Naples Federico II, Naples, Italy
8Hospital Universitario Virgen del Rocio, Seville, Spain
9Medical University of Gdansk, Gdansk, Poland
10Rush University, Chicago, IL
11ASST Grande, Ospedale Metropolitano Niguarda, Milano, Italy
12Incyte Corporation, Wilmington, DE
13IRCCS Azienda Ospedaliero-Universitaria di Bologna Istituto di Ematologia “Seràgnoli” and Dipartimento di Medicina Specialistica, Diagnostica e Sperimentale, Università di Bologna, Bologna, Italy

Background: Mantle cell lymphoma (MCL) is an aggressive type of non‐Hodgkin lymphoma (NHL) and accounts for 6% of all NHL cases in Western countries (Thandra KC. Med Sci. 2021;9:5). First-line treatment options are not curative and most patients (pts) experience relapse (Wu H. Front Oncol. 2020:10:588314; Kumar A. Blood Cancer J. 2019;9:50). Targeted therapies, including Bruton's tyrosine kinase (BTK) inhibitors, are used as second- and later-lines; however, treatment intolerance and failure are common with poor survival outcomes (Epperla N. Hematol Oncol. 2017;35:528–35; Jain P. Br J Haematol. 2018;182:404–11). Thus, novel therapies are needed for pts with relapsed or refractory (R/R) MCL. Parsaclisib is a potent, highly selective, next-generation inhibitor of phosphatidylinositol 3-kinase (PI3K) δ. Here, we report results of the primary analysis of the cohort of BTK inhibitor–naive pts with R/R MCL treated with parsaclisib monotherapy in the open-label, phase 2 study CITADEL-205 (NCT03235544, EudraCT 2017-003148-19).

Methods: Eligible pts were ≥18 years old, had pathologically confirmed MCL with documented cyclin D1 overexpression or t(11;14) translocation, and an Eastern Cooperative Oncology Group performance status (ECOG PS) ≤2. Pts must have received 1–3 prior systemic therapies and not had any prior treatment with a BTK and/or PI3K inhibitor. Pts were allocated to receive parsaclisib 20 mg once daily (QD) for 8 weeks followed by either 20 mg once weekly (weekly-dosing group [WG]) or 2.5 mg QD (daily-dosing group [DG]). Prophylaxis for Pneumocystis jirovecii pneumonia was required. The primary endpoint was objective response rate (ORR) as determined by an independent review committee (IRC); secondary endpoints included complete response rate (CRR), duration of response (DOR), overall survival (OS), progression-free survival (PFS), and safety and tolerability. All radiology-based endpoints were confirmed by an IRC.

Results: At data cutoff for the primary analysis (Jan 15, 2021), 108 pts naive to prior BTK inhibitor had been treated (WG, n=31; DG, n=77). Median (range) age was 72.0 (43–90) years, 79.6% of pts were male, 92.6% had ECOG PS ≤1, and median (range) time since initial diagnosis was 3.6 (0.1–20.9) years. Among all pts, 63.9% had received 1 line and 25.9% had received 2 lines of prior systemic therapy (median [range], 1 [1–3]); 31.5% of pts had prior hematopoietic stem cell transplant, and 50.0% had relapsed and 43.5% were refractory to their most recent prior therapy. 78 pts (72.2%) had discontinued treatment; primary reasons were progressive disease in 49 (45.4%) and adverse events in 25 (23.1%) pts. Median (range) treatment duration and follow-up from first dose to data cutoff were 8.3 (0.1–30.0) and 22.9 (11.6–35.9) months for all pts, and 7.9 (1.7–27.4) and 18.2 (11.6–35.9) months for DG, respectively. The ORR (95% CI) was 68.5% (58.9–77.1) for all pts and 70.1% (58.6–80.0) for the DG (Table 1); CRR (95% CI) was 17.6% (10.9–26.1) for all pts and 15.6% (8.3–25.6) for the DG. Among all treated pts with complete or partial response, 89.2% of responses occurred at the first disease assessment. Median (95% CI) DOR was 13.7 (9.0–19.9) months for all pts and 12.1 (9.0–not estimable) months for the DG. Median (95% CI) PFS was 11.99 (8.3–16.9) months for all pts and 13.6 (10.0–16.9) months for the DG. Median OS was not reached.

Among 108 treated pts, treatment-emergent adverse events (TEAEs) occurred in 90.7% (n=98) pts (grade ≥3 in 62.0% [n=67]). The most common TEAEs were diarrhea (34.3%), pyrexia (17.6%), and constipation (13.0%); most common grade ≥3 TEAEs were diarrhea (13.9%) and neutropenia (8.3%). TEAEs leading to dose interruption or dose reduction occurred in 47.2% and 8.3% of all pts, respectively. TEAEs led to treatment discontinuation in 25.0% of all pts; the most common were diarrhea (11.1%), colitis (4.6%), and hypokalemia (2.8%). Serious TEAEs occurred in 42.6% (n=46) of all pts; the most common were diarrhea (9.3%) and colitis (4.6%). Six pts (5.6%) overall experienced fatal TEAEs.

Conclusion: Parsaclisib monotherapy demonstrated a rapid and durable response, had an acceptable safety profile, and was generally well tolerated in BTK inhibitor–naive pts with R/R MCL. These data suggest that parsaclisib could be a potential treatment option for pts with R/R MCL.

Disclosures: Mehta: Seattle Genetics; Incyte; TG Therapeutics: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Seattle Genetics; Incyte; TG Therapeutics: Consultancy; Affirmed; Kite/Gilead; Roche-Genetech; Celgene/BMS; Oncotartis; Innate Pharmaceuticals; Seattle Genetics; Incyte; Takeda; Fortyseven Inc/Gilead; TG Therapeutics; Merck; Juno Pharmaceuticals/Bristol Myers Squibb: Research Funding. Trněný: Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses; MorphoSys: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses; Celgene: Consultancy; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses; 1st Faculty of Medicine, Charles University, General Hospital in Prague: Current Employment; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Portola: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses; Incyte: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Honoraria; Gilead Sciences: Consultancy, Honoraria, Other: Travel, Accommodations, Expenses; Bristol-Myers Squibb: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses. Walewski: Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Consultancy, Honoraria; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Servier: Consultancy, Honoraria. Ribrag: Incyte: Membership on an entity's Board of Directors or advisory committees; Epizyme: Honoraria, Research Funding; Nanostring: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees; GSK: Research Funding; Roche: Membership on an entity's Board of Directors or advisory committees; Argen-X: Research Funding; Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees; Servier: Consultancy, Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Membership on an entity's Board of Directors or advisory committees; Gilead: Membership on an entity's Board of Directors or advisory committees; PharmaMar: Honoraria, Membership on an entity's Board of Directors or advisory committees; MSD Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Infinity Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Astex Pharmaceuticals: Research Funding. Dartigeas: Astra-Zeneca: Membership on an entity's Board of Directors or advisory committees, Other: travel grants/Congress; Abbvie: Membership on an entity's Board of Directors or advisory committees, Other: travel grants/Congress; Janssen: Membership on an entity's Board of Directors or advisory committees, Other: travel grants/Congress. Pane: AbbVie; Amgen; Novartis: Other: Travel, accommodation, expenses; Novartis Pharma SAS;: Research Funding; AbbVie; Amgen; Novartis, GSK , Incyte: Consultancy; AbbVie; Amgen; Novartis, GSK, Incyte: Speakers Bureau; Daiichi Sankyo: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, ; Janssen: Other: Travel, Accommodations, ; Jazz Pharmaceuticals: Consultancy, Other: Travel, Accommodations, Speakers Bureau. Rodriguez: Bristol-Myers Squibb; Celgene; EUSA Pharma; Janssen; Roche; Takeda: Consultancy; Bristol-Myers Squibb; Celgene; Janssen; Roche; Takeda: Speakers Bureau. Taszner: Roche, Takeda: Consultancy, Other: Travel. Zilioli: Takeda: Other: travel expenses, accommodation; Roche, Italfarmaco: Consultancy, Honoraria; MSD, Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations; Gentili, Takeda, Gilead, Servier: Consultancy, Speakers Bureau. Zheng: Incyte Corporation: Current Employment, Current equity holder in publicly-traded company. DeMarini: Incyte: Current Employment, Current equity holder in publicly-traded company. Jiang: Incyte: Current Employment, Current equity holder in publicly-traded company. Zinzani: Portola: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Servier: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celltrion: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen-Cilag: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BeiGene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; ImmuneDesign: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees; Verastem: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Bristol Myers Squibb: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Kyowa Kirin: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; TG Therapeutics Inc: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sandoz: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Incyte: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Merck Sharp & Dohme: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; ADC Therapeutics: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; EUSA Pharma: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.

OffLabel Disclosure: Investigational PI3Kdelta inhibitor (parsaclisib) for patients with MCL

*signifies non-member of ASH