A Study of INCB050465 in Subjects With Relapsed or Refractory Marginal Zone Lymphoma (CITADEL-204)

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety and efficacy of two parsaclisib treatment regimens in participants diagnosed with relapsed or refractory marginal zone lymphoma (MZL) who are naive to or were previously treated with a Bruton's tyrosine kinase (BTK) inhibitor.

Official Title
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A Phase 2, Open-Label, 2-Cohort Study of INCB050465, a PI3Kδ Inhibitor, in Subjects With Relapsed or Refractory Marginal Zone Lymphoma With or Without Prior Exposure to a BTK Inhibitor (CITADEL-204)

Conditions
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Lymphoma

Intervention / Treatment
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* Drug: Parsaclisib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men and women, aged 18 or older (except in South Korea, aged 19 or older). Histologically confirmed marginal zone lymphoma, including extranodal, nodal, and splenic subtypes. Radiographically measurable lymphadenopathy or extranodal lymphoid malignancy (defined as the presence of ≥ 1 lesion that measures > 1.5 cm in the longest transverse diameter and ≥ 1.0 cm in the longest perpendicular diameter. Participants with splenic MZL who do not meet the radiographically measurable disease criteria described herein are eligible for participation provided that bone marrow infiltration of MZL is histologically confirmed. Participants must be willing to undergo an incisional or excisional lymph node or tissue biopsy or provide a lymph node or tissue biopsy from the most recent available archival tissue. Eastern Cooperative Oncology Group performance status 0 to 2. Exclusion Criteria: Evidence of diffuse large B-cell transformation. History of central nervous system lymphoma (either primary or metastatic) or leptomeningeal disease. Prior treatment with idelalisib, other selective PI3Kδ inhibitors, or a pan-PI3K inhibitor. 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 treatment. Active graft versus host disease. Subjects positive for hepatitis B surface antigen or hepatitis B core antibody will be eligible if they are negative for HBV-DNA. Subjects positive for anti-HCV antibody will be eligible if they are negative for HCV-RNA.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1- Closed to Further enrollment<br>Participants who have received prior ibrutinib. | Drug: Parsaclisib<br>* Parsaclisib at the protocol-defined dose.<br>* Other names: INCB050465;|
| Experimental: Cohort 2<br>Participants who have not received a prior BTK inhibitor. | Drug: Parsaclisib<br>* Parsaclisib at the protocol-defined dose.<br>* Other names: INCB050465;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) Based on Lugano Classification Criteria | ORR=percentage of participants with complete response(CR) or partial response(PR) per revised response criteria for lymphomas,determined by independent review committee(IRC).Criteria for CR:1.Target nodes/nodal masses of lymph nodes,extralymphatic sites regressed to≤1.5cm in longest dimension transverse diameter of lesion(LDi);2.Absence of non-measured lesion;3.Organ enlargement regressed to normal;4.No new lesions;5.Normal bone marrow morphology;if indeterminate,immunohistochemistry negative.Criteria for PR:1.Lymph nodes,extralymphatic sites- ≥50%decrease in sum of product of perpendicular diameters for multiple lesions(SPD)of up to 6 target measurable nodes,extranodal sites;if lesion is too small to measure on computed tomography(CT),assign 5mm×5mm as default;if no longer visible,0×0mm.Node >5mm×5mm but smaller than normal,use actual measurement.2.Absent/regressed non-measured lesions,no increase.3.Organ enlargement-Spleen regressed by >50%in length beyond normal.4.No new lesions. | Up to approximately 161 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of Response (DOR) | DOR=time from first documented evidence of CR or PR until disease progression or death from any cause among participants who achieve an objective response as determined by IRC. Criteria for CR: 1.Target nodes/nodal masses of lymph nodes and extralymphatic sites must regress to ≤ 1.5 cm in LDi; 2. Absence of non-measured lesion; 3.Organ enlargement regressed to normal; 4.No new lesions; 5.Bone marrow must be normal by morphology; if indeterminate, immunohistochemistry negative. The criteria for PR included: 1.Lymph nodes and extralymphatic sites- a. ≥50% decrease in SPD of up to 6 target measurable nodes and extranodal sites; b. when a lesion is too small to measure on CT, assign 5 mm×5 mm as the default; c.when no longer visible, 0×0 mm. For a node >5 mm×5 mm but smaller than normal, use actual measurement. 2.Non-measured lesions- Absent/regressed, but no increase. 3. Organ enlargement-Spleen must have regressed by >50% in length beyond normal. 4.No new lesions. | Up to approximately 161 weeks | 
| Complete Response Rate (CRR) Based on Lugano Classification Criteria | CRR is defined as the percentage of participants with a CR as determined by an IRC. The criteria for CR included: 1.Target nodes/nodal masses of lymph nodes and extralymphatic sites must regress to ≤ 1.5 cm in LDi; 2. Absence of non-measured lesion; 3.Organ enlargement regressed to normal; 4.No new lesions; 5.Bone marrow must be normal by morphology; if indeterminate, immunohistochemistry negative. | Up to approximately 161 weeks | 
| Progression-Free Survival (PFS) | PFS is defined as the time from the date of the first dose of study treatment until the earliest date of disease progression, as determined by radiographic disease assessment provided by an IRC, or death from any cause. | Up to approximately 161 weeks | 
| Overall Survival (OS) | OS is defined as the time from the date of the first dose of study treatment until death from any cause. | Up to approximately 161 weeks | 
| Best Percent Change From Baseline in Target Lesion Size | Target lesion size is measured by the sum of the product of diameters of all target lesion sizes and is determined by the IRC. The best percent change from Baseline is defined as the largest decrease, or smallest increase (if no decrease available), from Baseline in target lesion sizes on/before new (next-line) anti-lymphoma therapy during the study. Baseline is the last nonmissing measurement obtained before the first administration of study drug. A negative percent change from Baseline indicates improvement. | Up to approximately 161 weeks | 
| Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | An adverse event (AE) is any untoward medical occurrence associated with use of a drug in humans, whether or not considered drug related, that occurs after a participant provides informed consent. A TEAE is any AE either reported for the first time or worsening of a pre-existing event after first dose of study drug and within 30 days of the last administration of study drug regardless of starting new anti-lymphoma therapy. A SAE is any untoward medical occurrence that results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, leads to a congenital anomaly/birth defect or is considered to be an important medical event that may not result in death, be immediately life-threatening, or require hospitalization but may be considered serious when, based on appropriate medical judgment, the event may jeopardize the participant or may require medical or surgical intervention. | From first dose of study drug up to approximately 161 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Marginal zone lymphoma, phosphatidylinositol 3-kinase (PI3K)δ inhibitor, indolent (slow-growing) non-Hodgkin lymphoma B-cell lymphoma