On December 7, 2020 Incyte (Nasdaq:INCY) reported data from three ongoing Phase 2 studies evaluating parsaclisib, a potent, highly selective, next-generation oral inhibitor of phosphatidylinositol 3-kinase delta (PI3Kδ), for the treatment of patients with relapsed or refractory follicular (CITADEL-203), marginal zone (CITADEL-204) and mantle cell (CITADEL-205) lymphomas (Press release, Incyte, DEC 7, 2020, View Source [SID1234572326]). These data were accepted for presentation at the 62nd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition (ASH 2020), held virtually from December 5–8, 2020.

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The primary endpoint for the CITADEL-203, -204 and -205 studies is objective response rate (ORR); duration of response (DOR), progression-free survival (PFS), overall survival (OS), safety and tolerability are among the secondary endpoints. All radiology-based endpoints are based on independent review committee (IRC) assessment.

Eligible patients received parsaclisib 20 mg once daily for eight weeks followed by either 20 mg once weekly (weekly-dosing group [WG]) or 2.5 mg once daily (daily-dosing group [DG]). Subsequently, daily dosing was selected as the preferred regimen and patients initially enrolled in the WG were allowed to switch to DG. Data are presented for the DG and all patients.

Key results from the CITADEL studies include:

ORR (95% CI), %

mDOR (95% CI),

months

mPFS (95% CI),

months

mOS (95% CI),

months

CITADEL-203: R/R Follicular Lymphoma

DG (N=95)

75 (65-83)

14.7 (12.0-17.5)

15.8 (13.8-19.1)

–

All (N=118)

73 (64-81)

15.9 (12.0-NE)

15.8 (13.2-19.3)

–

CITADEL-204: R/R Marginal Zone Lymphoma

DG (N=72)

56.9 (44.7-68.6)

NR (8.1-NE)

NR (11.0-NE)

–

All (N=100)

57.0 (46.7-66.9)

12.0 (9.3-NE)

19.4 (13.7-NE)

–

CITADEL-205: R/R Mantle Cell Lymphoma (BTK Inhibitor Treatment Naive)

DG (N=77)

71 (60-81)

9.0 (6.7-14.7)

11.1 (8.3-NE)

NR (NE-NE)

All (N=108)

70 (61-79)

14.7 (7.7-NE)

11.1 (8.3-19.2)

NR (NE-NE)

CITADEL-205: R/R Mantle Cell Lymphoma (Previously Treated with Ibrutinib)

DG (N=41)

29 (16-46)

3.7 (1.9-NE)

3.7 (1.8-4.1)

11.2 (7.9-NE)

All (N=53)

25 (14-38)

3.7 (1.9-NE)

3.7 (1.8-3.9)

11.2 (7.9-17.1)

R/R: relapsed or refractory; ORR: objective response rate; mDOR: median duration of response (reported for responders); mPFS: median progression-free survival; mOS: median overall survival; DG: daily dosing group; BTK: Bruton’s tyrosine kinase.

Parsaclisib was generally well tolerated in all studies with a manageable safety profile.

"Data from the CITADEL studies presented at ASH (Free ASH Whitepaper) 2020 are very promising and they highlight the potential of parsaclisib to become a meaningful treatment for patients with relapsed or refractory follicular, marginal zone or mantle cell lymphomas," said Peter Langmuir, M.D., Group Vice President, Oncology Targeted Therapies, Incyte. "We look forward to continuing our work as we seek to bring this medicine to patients."

Presentations are available on the ASH (Free ASH Whitepaper) website at View Source; #338 (Oral presentation, CITADEL-204), #2935 (Poster, CITADEL-203), #1121 (Poster, CITADEL-205), #2044 (Poster, CITADEL-205).

About Follicular, Marginal Zone and Mantle Cell Lymphomas

Non-Hodgkin lymphoma (NHL) is a type of cancer that starts in the lymphocytes, a type of white blood cell. Follicular lymphoma (FL), marginal zone lymphoma (MZL) and mantle cell lymphoma (MCL) are forms of B-Cell NHLs. FL and MZL are indolent or slow growing lymphomas; MCL is an aggressive or rapidly developing form. There is an unmet medical need for treatment options for patients who are relapsed or refractory to initial therapies.

About CITADEL

The CITADEL (Clinical Investigation of TArgeted PI3K-DELta Inhibition in Lymphomas) clinical trial program is evaluating parsaclisib in several ongoing studies as a treatment for adult patients with lymphomas, including:

CITADEL-203 (NCT03126019) is evaluating patients with relapsed or refractory follicular lymphoma (FL) Grade 1, 2 or 3a who received at least two prior systemic therapies, had an Eastern Cooperative Oncology Group performance status (ECOG PS) ≤2, and were ineligible for hematopoietic stem cell transplantation (HSCT).
CITADEL-204 (NCT03144674) is evaluating patients with relapsed or refractory marginal zone lymphoma (MZL) who received at least one prior systemic therapy and were Bruton’s tyrosine kinase (BTK) inhibitor treatment naive. Patients with prior ibrutinib treatment were initially allowed to enroll; however, the cohort was terminated due to slow enrollment. Eligible patients had radiologically measurable lymphadenopathy or extranodal lymphoid malignancy (or histologically confirmed bone marrow infiltration in cases of splenic MZL), and an ECOG PS ≤2.
CITADEL-205 ( NCT03235544 ) is evaluating patients with relapsed or refractory mantle cell lymphoma (MCL), who received one to three prior systemic therapies and were either naive to or were previously treated with a BTK inhibitor. Eligible patients had an ECOG PS ≤2, and radiologically measurable lymphadenopathy or extranodal lymphoid malignancy.
Patients eligible for each trial were allocated to receive parsaclisib 20 mg once daily for eight weeks followed by either 20 mg once weekly (weekly-dosing group [WG]) or 2.5 mg once daily (daily-dosing group [DG]). Subsequently, daily dosing was selected as the preferred regimen and the WG patients were allowed to switch to DG. Prophylaxis for Pneumocystis jirovecii pneumonia (PJP) was required.

About Parsaclisib

Parsaclisib is a potent, highly selective, next-generation investigational novel oral inhibitor of phosphatidylinositol 3-kinase delta (PI3Kδ). It is currently under evaluation as a monotherapy in several ongoing Phase 2 trials as a treatment for non-Hodgkin lymphomas (follicular, marginal zone and mantle cell); and autoimmune hemolytic anemia. Pivotal trials of parsaclisib in combination with ruxolitinib for the treatment of patients with myelofibrosis are underway; and there are plans to initiate a trial to evaluate parsaclisib in combination with tafasitamab for B-cell malignancies.

In December 2018, Innovent and Incyte entered into a strategic collaboration for three clinical-stage product candidates, including parsaclisib. Under the terms of the agreement, Innovent has received the rights to develop and commercialize parsaclisib and two other assets in Mainland China, Hong Kong, Macau and Taiwan.

Conference Call Information

Incyte will host an investor conference call and webcast at 10:00 a.m. ET (7:00 a.m. PT) today, December 7, 2020—the call and webcast can be accessed via the Events and Presentations tab of the Investor section of Incyte.com and it will be available for replay for 90 days.