A Study of INCB050465 in Relapsed or Refractory Follicular Lymphoma

Study Overview
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Brief Summary
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The purpose of this study is to assess the objective response rate of parsaclisib treatment in participants with relapsed or refractory follicular lymphoma.

Official Title
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A Phase 2, Multicenter, Open-Label Study of INCB050465, a PI3Kδ Inhibitor in Relapsed or Refractory Follicular Lymphoma (CITADEL-203)

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: Aged 18 years or older. Histologically confirmed, relapsed or refractory, follicular B-cell non-Hodgkin lymphoma (NHL) (follicular lymphoma) Grade 1, 2, and 3a. Ineligible for hematopoietic stem cell transplant. Must have been treated with at least 2 prior systemic therapies. Radiographically measurable lymphadenopathy or extranodal lymphoid malignancy (defined as the presence of ≥ 1 lesion that measures > 1.5 cm in the longest dimension and ≥ 1.0 cm in the longest perpendicular dimension as assessed by computed tomography or magnetic resonance imaging. Must be willing to undergo an incisional, excisional, or core needle lymph node or tissue biopsy or provide a lymph node or tissue biopsy from the most recent available archival tissue. Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2. Exclusion Criteria: Known histological transformation from indolent NHL to diffuse large B-cell lymphoma. History of central nervous system lymphoma (either primary or metastatic). Prior treatment with idelalisib, other selective phosphatidylinositol 3-kinase delta (PI3Kδ) inhibitors, or a pan-PI3K inhibitor. Prior treatment with a Bruton's tyrosine kinase inhibitor (eg, ibrutinib). Allogeneic stem cell transplant within the last 6 months, or autologous stem cell transplant within the last 3 months before the date of study treatment administration. Active graft-versus-host disease. Participants positive for hepatitis B surface antigen or hepatitis B core antibody will be eligible if they are negative for hepatitis B virus-deoxyribonucleic acid (HBV-DNA). Participants positive for anti-hepatitis C virus (HCV) antibody will be eligible if they are negative for HCV-ribonucleic acid (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: Treatment A: Parsaclisib 20 mg QD for 8 Weeks Followed by 20 mg QW<br>Participants received parsaclisib 20 mg once daily (QD) for 8 weeks followed by 20 mg once weekly (QW) for up to approximately 52 weeks. | Drug: Parsaclisib<br>* Parsaclisib tablets administered orally with water and without regard to food<br>* Other names: INCB050465;|
| Experimental: Treatment B: Parsaclisib 20 mg QD for 8 Weeks Followed by 2.5 mg QD<br>Participants received parsaclisib 20 mg QD for 8 weeks followed by 2.5 mg QD for up to approximately 52 weeks. | Drug: Parsaclisib<br>* Parsaclisib tablets administered orally with water and without regard to food<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 With Parsaclisib Based on Lugano Classification Response 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),assign5mm×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 148 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete Response Rate With Parsaclisib Based on Lugano Classification Response Criteria | CRR was defined as the percentage of participants with a CR as defined by revised response criteria for lymphomas 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 148 weeks | 
| 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 148 weeks | 
| Progression-free Survival (PFS) With Parsaclisib | PFS was 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 148 weeks | 
| Overall Survival (OS) With Parsaclisib | OS was defined as the time from the date of the first dose of study treatment until death from any cause. | Up to approximately 148 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 non-missing measurement obtained before the first administration of study drug. A negative percent change from Baseline indicates improvement. | Up to approximately 148 weeks | 
| Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | An adverse event (AE) is defined as 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. TEAE is any AE either reported for first time or worsening of a pre-existing event after first dose of study drug and within 30 days of last administration of study drug regardless of starting new anti-lymphoma therapy. 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 148 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Follicular lymphoma, non-Hodgkin lymphoma (NHL), phosphatidylinositol 3-kinase (PI3K) δ inhibitor