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Nov. 22, 2018

Dec. 22, 2023

jRCT2080224158

A Phase 1b, Open-Label, Dose-Escalation Study for the Safety, Tolerability, and Pharmacokinetics of INCB050465 in Japanese Subjects With Previously Treated B-Cell Lymphoma (CITADEL-111)

A Study of INCB050465 in Japanese Subjects With Previously Treated B-Cell Lymphoma (CITADEL-111)

Aug. 14, 2020

17

All participants were Japanese, and the majority were > 65 years old (58.8%) and female (64.7%).

A total of 17 participants were enrolled and received at least 1 dose of parsaclisib monotherapy at 10 mg QD (n = 3) or 20 mg QD (n = 14) followed by the same dose once weekly. Six participants (35.3%) remained on treatment and 7 participants (41.2%) overall remained on study.

TEAEs occurred in 100.0% of participants.

No DLTs occurred at the 10 mg dose level: DLTs occurred in 2 of 14 participants at the 20 mg dose level during the dose expansion phase, and included Grade 3 febrile neutropenia and Grade 4 neutropenia in 1 participant each. The 20 mg dose level was determined not to have exceeded the MTD. No clinically meaningful trends in clinical chemistry or changes in vital signs, body weight, or ECGs occurred with parsaclisib administration. A majority of shifts from baseline to low neutrophil counts were to CTC Grade 1 or Grade 2. No clinically significant elevations in transaminases were noted during the study. After oral administration in the fasted state, parsaclisib plasma concentrations attained peak values (C max) typically at 0.55 to 1 hour (median Tmax) postdose, and subsequently exhibited a mono- or bi-exponential decay with a steady-state geometric mean terminal-phase disposition half-life (t1/2 1/2) of approximately 9.94 hours and a systemic accumulation ratio of approximately 1.3. Steady-state oral-dose clearance (C Lss / F) and volume of distribution (Vz / F) of parsaclisib were 2.18 plus or minus 0.723 L/h and 31.2 plus or minus 9.77 L, respectively. Body weight normalized CLss/F and body weight normalized Vz / F were comparable between Japanese participants in this study and US participants in study INCB 50465-101. The mean (range) percentage of parent compound excreted in urine as unchanged parsaclisib at steady-state over the 0 to 8 hour collection interval was 12.1% (5.4%-20.4%) following 10 mg and 20 mg QD administration combined, and the man plus or minus STD of the renal clearance was 0.432 plus or minus 0.171 L/h.

The ORR for the 6 participants with DLBCL was 16.7% (95% CI: 0.42, 64.12). A single responder had PR/PMR as best overall response that was maintained at the last assessment.The ORR for the 9 participants with FL was 100.0% (95% CI: 66.37, 100.0), including 2 participants (22.2%) with CR/CMRs and 7 participants (77.8%) with PR/PMRs as best overall response.Two participants had CR/CMRs and 1 participant had PR/PMR as best overall response that was maintained at the last assessment.The ORR for the 2 participants with MZL was 100.0% (95% CI: 15.81, 100.0). Both participants had PR/PMRs as best overall response that was maintained at the last assessment .

Parsaclisib was shown to be safe and tolerable in Japanese participants with relapsed or refractory B-cell malignancies at parsaclisib 20 mg QD for 8 weeks followed by the same dose once weekly. Parsaclisib was not associated with significant transaminase elevations or with any new or unexpected AEs in the Japanese population. Based on preliminary analyses, the PK profile of parsaclisib in Japanese participants is comparable to the profile in the US population and no dose modifications are recommended.

Dec. 22, 2023

Yes

Data will be made available at the end of trial or termination of trial. The following data will be made available: safety, PK and PD, efficacy, and subject characteristics. The results of the trial will be published. In addition, data as documented in study CSR will be made available upon request.

version:
date:Sept. 07, 2022

Incyte Biosciences Japan G.K.

Tokyo Midtown Hibiya 1-1-2 Yurakucho, Chiyoda-ku, Tokyo, Japan

+81-120-094-139

jpmedinfo@incyte.com

Incyte Biosciences Japan G.K.

Tokyo Midtown Hibiya 1-1-2 Yurakucho, Chiyoda-ku, Tokyo, Japan

+81-120-094-139

jpmedinfo@incyte.com

completed

Aug. 02, 2018

17

Interventional

Intervention Model: Single Group Assignment Masking: None (Open Label) Primary Purpose: Treatment

treatment purpose

1

1) First generation Japanese; subject was born in Japan and has not lived outside of Japan for > 10 years, and subject can trace maternal and paternal Japanese ancestry.
2) Histologically confirmed aggressive/indolent DLBCL, FL, MZL, or MCL.
3) Previously received at least 1 prior line of systemic therapy with documented progression, and there is no further effective standard anticancer therapy available.
4) Willing to undergo an incisional or excisional lymph node or tissue biopsy or to provide a lymph node or tissue biopsy from the most recent available archival tissue.
5) Life expectancy > 3 months.
6) Eastern Cooperative Oncology Group performance status of 0 to 2.
7) Adequate hematologic, hepatic, and renal function.

1) Evidence of transformed non-Hodgkin's lymphoma histologies.
2) Histologically confirmed, rare non-Hodgkin's B-cell subtypes.
3) History of central nervous system lymphoma (either primary or metastatic) or leptomeningeal disease.
4) Prior treatment with idelalisib, other selective PI3K delta inhibitors, or a pan-phosphatidylinositol 3 kinase (PI3K) inhibitor.
5) Allogeneic stem cell transplant within the last 6 months or autologous stem cell transplant within the last 3 months before the date of the first dose of study drug.
6) Active graft-versus-host disease.
7) History of stroke or intracranial hemorrhage within 6 months of study drug administration.
8) Chronic or current active infectious disease requiring systemic antibiotics, antifungal, or antiviral treatment or exposure to a live vaccine within 30 days of the date of the first dose of study drug.
9) Known human immunodeficiency virus infection.
10) Evidence of hepatitis B virus or hepatitis C virus infection or risk of reactivation.

20age old over
No limit

Both

Lymphoma

investigational material(s)
Generic name etc : INCB050465
INN of investigational material : -
Therapeutic category code : 429 Other antitumor agents
Dosage and Administration for Investigational material : INCB050465 administered orally once daily for 8 weeks at the protocol-defined dose, followed by a once-weekly regimen at the same dose.

control material(s)
Generic name etc : -
INN of investigational material : -
Therapeutic category code :
Dosage and Administration for Investigational material : -

safety
Number of participants with treatment-emergent adverse events
TEAE defined as any adverse event either reported for the first time or worsening of a pre-existing event after first dose of study drug.

efficacy
pharmacokinetics
1.Changes in pharmacodynamic (PD) markers of B-cell activation in plasma
2.Objective response rate
3.Duration of response
4.Progression-free survival

1. Markers of B-cell activation (eg, B-cell activating factor, interleukin-10, B-cell attracting chemokine) and other plasma analytes will be analyzed for correlation with safety and clinical outcome.
2. Defined as the percentage of subjects with complete response (CR)/complete metabolic response (CMR) and partial response (PR)/ partial metabolic response (PMR), as determined by investigator assessment of response according to response criteria for lymphomas.
3. Defined as the time from first documented evidence of CR/CMR or PR/PMR until disease progression or death from any cause among subjects who achieve an objective response.
4. Defined as the time from the date of the first dose of study drug until the earliest date of disease progression or death from any cause.

Incyte Corporation
-
-
-
National University Corporation Tohoku University Tohoku University Hospital Institutional Review Board
1-1 Seiryo-machi, Aoba-ku, Sendai-shi, Miyagi, Japan

-

-
approved

May. 28, 2020

NCT03314922
ClinicalTrials.gov
JapicCTI-184219
Japan

History of Changes

No Publication date
8 Dec. 22, 2023 (this page) Changes
7 Sept. 06, 2023 Detail Changes
6 June. 28, 2022 Detail Changes
5 June. 17, 2021 Detail Changes
4 July. 14, 2020 Detail Changes
3 Dec. 17, 2018 Detail Changes
2 Nov. 22, 2018 Detail Changes
1 Nov. 22, 2018 Detail