Lymphoma
Conditions
Keywords
Diffuse large B-cell lymphoma, relapsed, refractory, non-Hodgkin lymphoma, phosphatidylinositol 3-kinase δ (PI3Kδ) inhibitor, Bruton's tyrosine kinase (BTK)
Brief summary
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.
Interventions
DRUGParsaclisib
Parsaclisib once daily for 8 weeks followed by once weekly
Sponsors
Incyte Corporation
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate Based on Lugano Classification Criteria in Group A | Every 9 weeks through Week 27, then every 18 weeks thereafter until disease progression, up to 26 months | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Response in Group A | Every 9 weeks through Week 27, then every 18 weeks thereafter until disease progression, up to 26 months | 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. |
| Progression-free Survival in Group A | Every 9 weeks through Week 27, then every 18 weeks thereafter until disease progression, up to 26 months | 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. |
| Overall Survival (OS) in Group A | From first dose of study drug until death by any cause; up to 26 months | Defined as the time from the date of the first dose of study drug until death by any cause. |
| Safety as Assessed by Percentage of Subjects With Adverse Events in Group A and Group B | Screening through 35 days after end of treatment, up to 42 months | 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. |
Countries
Australia, Belgium, Canada, Czechia, France, Italy, Poland, South Korea, Spain, United Kingdom, United States
Participant flow
Recruitment details
A Phase 2, multicenter, international, open-label study with approximately 120 planned participants with relapsed or refractory DLBCL.
Pre-assignment details
55 participants included in the treatment group A who were not previously treated with a BTK inhibitor and received parsaclisib 20 mg QD for 8 weeks followed by 20 mg QW. 5 Participants were enrolled in group B who were previously treated with a BTK inhibitor. and received parsaclisib 20 mg QD for 8 weeks followed by 20 mg QW.
Participants by arm
| Arm | Count |
|---|---|
| Group A Parsaclisib (no Prior BTK Inhibitor) Parsaclisib in subjects who were not previously treated with a BTK inhibitor. | 55 |
| Group B Parsaclisib (Prior BTK Inhibitor) Parsaclisib in subjects who were previously treated with a BTK inhibitor. | 5 |
| Total | 60 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 45 | 2 |
| Overall Study | Lost to Follow-up | 1 | 0 |
| Overall Study | Other | 6 | 1 |
| Overall Study | Participants transferred to rollover study INCB50465-801 | 2 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 2 |
Baseline characteristics
| Characteristic | Group A Parsaclisib (no Prior BTK Inhibitor) | Group B Parsaclisib (Prior BTK Inhibitor) | Total |
|---|---|---|---|
| Age, Continuous | 69.6 years STANDARD_DEVIATION 12.62 | 68.4 years STANDARD_DEVIATION 12.97 | 69.5 years STANDARD_DEVIATION 12.54 |
| ECOG 0 | 12 Participants | 1 Participants | 13 Participants |
| ECOG 1 | 34 Participants | 3 Participants | 37 Participants |
| ECOG 2 | 9 Participants | 1 Participants | 10 Participants |
| Race/Ethnicity, Customized Asian | 3 Participants | 0 Participants | 3 Participants |
| Race/Ethnicity, Customized Black or African American | 2 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized Missing | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 37 Participants | 5 Participants | 42 Participants |
| Race/Ethnicity, Customized Not Reported | 10 Participants | 0 Participants | 10 Participants |
| Race/Ethnicity, Customized Other | 6 Participants | 0 Participants | 6 Participants |
| Race/Ethnicity, Customized Unknown | 7 Participants | 0 Participants | 7 Participants |
| Race/Ethnicity, Customized White/Caucasian | 42 Participants | 5 Participants | 47 Participants |
| Sex: Female, Male Female | 22 Participants | 0 Participants | 22 Participants |
| Sex: Female, Male Male | 33 Participants | 5 Participants | 38 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 45 / 55 | 3 / 5 | 48 / 60 |
| other Total, other adverse events | 41 / 55 | 3 / 5 | 44 / 60 |
| serious Total, serious adverse events | 39 / 55 | 2 / 5 | 41 / 60 |
Outcome results
Primary
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.
Time frame: Every 9 weeks through Week 27, then every 18 weeks thereafter until disease progression, up to 26 months
Population: The full analysis set includes all subjects enrolled in the study who received at least 1 dose of INCB050465
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group A Parsaclisib (no Prior BTK Inhibitor) | Objective Response Rate Based on Lugano Classification Criteria in Group A | 25.5 percentage |
Secondary
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.
Time frame: Every 9 weeks through Week 27, then every 18 weeks thereafter until disease progression, up to 26 months
Population: The full analysis set includes all subjects enrolled in the study who received at least 1 dose of INCB050465
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Group A Parsaclisib (no Prior BTK Inhibitor) | Duration of Response in Group A | 6.2 months |
Secondary
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.
Time frame: From first dose of study drug until death by any cause; up to 26 months
Population: The full analysis set includes all subjects enrolled in the study who received at least 1 dose of INCB050465
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Group A Parsaclisib (no Prior BTK Inhibitor) | Overall Survival (OS) in Group A | 7.0 months |
Secondary
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.
Time frame: Every 9 weeks through Week 27, then every 18 weeks thereafter until disease progression, up to 26 months
Population: The full analysis set includes all subjects enrolled in the study who received at least 1 dose of INCB050465
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Group A Parsaclisib (no Prior BTK Inhibitor) | Progression-free Survival in Group A | 2.2 months |
Secondary
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.
Time frame: Screening through 35 days after end of treatment, up to 42 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Group A Parsaclisib (no Prior BTK Inhibitor) | Safety as Assessed by Percentage of Subjects With Adverse Events in Group A and Group B | 50 Participants |
| Group B Parsaclisib (Prior BTK Inhibitor) | Safety as Assessed by Percentage of Subjects With Adverse Events in Group A and Group B | 4 Participants |