A Phase 2 Safety and Efficacy Study of INCB050465 in Subjects With Relapsed or Refractory Diffuse Large B-Cell Lymphoma (CITADEL-202)

Study Overview
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Brief Summary
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The purpose of this study is to assess the safety and efficacy of parsaclisib in subjects with relapsed or refractory diffuse large B-cell lymphoma.

Official Title
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A Phase 2, Multicenter, International, Open-Label, Safety and Efficacy Study of INCB050465 in Subjects With Relapsed or Refractory Diffuse Large B-Cell Lymphoma (CITADEL-202)

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: Eligible 19 years and older in South Korea Relapsed or refractory DLBCL, which has been histologically documented, defined as having received at least 2 but no more than 5 prior treatment regimens and ineligible for high-dose chemotherapy supported by autologous stem cell transplant. Must have ≥ 1 measurable lesion (≥2 cm in longest dimension) or ≥ 1 measurable extranodal lesion (≥1 cm in longest dimension) on computed tomography (CT) scan or magnetic resonance imaging (MRI). Subjects must be willing to undergo an incisional or excisional lymph node biopsy of accessible adenopathy or provide the most recent, available archived tumor biopsy. Eastern Cooperative Oncology Group performance status 0 to 2. Exclusion Criteria: Primary mediastinal (thymic) large B-cell lymphoma. Known brain or central nervous system metastases or history of uncontrolled seizures. Allogeneic stem cell transplant within the last 6 months, or active graft versus host disease following allogeneic transplant, or autologous stem cell transplant within the last 3 months. Use or expected use during the study of any prohibited medications, including potent cytochrome P450 3A4 inhibitors or inducers within 14 days or 5 half lives (whichever is longer) before the first dose of study drug. Prior treatment with the following: Group A: Prior treatment with a selective phosphatidylinositol 3-kinase (PI3K) δ inhibitor (eg, idelalisib), a pan-PI3K inhibitor, or a BTK inhibitor (eg, ibrutinib). Group B: Prior treatment with a selective PI3Kδ inhibitor (eg, idelalisib) or a pan PI3K inhibitor.

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: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group A Parsaclisib (no prior BTK inhibitor)<br>Parsaclisib in subjects who were not previously treated with a BTK inhibitor. | Drug: Parsaclisib<br>* Parsaclisib once daily for 8 weeks followed by once weekly<br>* Other names: INCB050465;|
| Experimental: Group B Parsaclisib (prior BTK inhibitor)<br>Parsaclisib in subjects who were previously treated with a BTK inhibitor. | Drug: Parsaclisib<br>* Parsaclisib once daily for 8 weeks followed by once weekly<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 Based on Lugano Classification Criteria in Group A | Defined as the percentage of subjects with a complete or partial response as defined by Lugano Classification criteria for lymphomas (Cheson et al 2014) as determined by IRC. | Every 9 weeks through Week 27, then every 18 weeks thereafter until disease progression, up to 26 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of Response in Group A | Defined as the time from first documented evidence of complete or partial response until disease progression or death from any cause among subjects who achieve an objective response as determined by IRC. | Every 9 weeks through Week 27, then every 18 weeks thereafter until disease progression, up to 26 months | 
| Progression-free Survival in Group A | Defined as the time from the date of the first dose of study drug until the earliest date of disease progression, as determined by radiographic disease assessment as provided by an IRC. | Every 9 weeks through Week 27, then every 18 weeks thereafter until disease progression, up to 26 months | 
| Overall Survival (OS) in Group A | Defined as the time from the date of the first dose of study drug until death by any cause. | From first dose of study drug until death by any cause; up to 26 months | 
| Safety as Assessed by Percentage of Subjects With Adverse Events in Group A and Group B | A TEAE is any AE either reported for the first time or worsening of a pre-existing event after the first dose of parsaclisib until 30 days after the last dose administration. | Screening through 35 days after end of treatment, up to 42 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Diffuse large B-cell lymphoma, relapsed, refractory, non-Hodgkin lymphoma, phosphatidylinositol 3-kinase δ (PI3Kδ) inhibitor, Bruton's tyrosine kinase (BTK)