Lymphoma
Conditions
Keywords
Follicular Lymphoma, Parsaclisib, PI3Kδ Inhibitor
Brief summary
The purpose of this study is to assess the efficacy and safety of parsaclisib in Japanese participants with relapsed or refractory follicular lymphoma
Interventions
DRUGparsaclisib
parsaclisib will be taken orally QD with water without regard to food except on mornings of PK clinic visits
Sponsors
Incyte Biosciences Japan GK
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male or female Japanese participant who must be ≥ 18 years of age * Ability to comprehend and willingness to sign a written ICF and comply with all study visits and procedures * Histologically confirmed, relapsed or refractory, FL Grade 1, 2, and 3a * Ineligible for HSCT * Must have been treated with at least 2 prior systemic therapies for FL * Radiographically measurable lymphadenopathy or extranodal lymphoid malignancy (defined as the presence of ≥ 1 lesion that measures \> 1.5 cm in the LD and ≥ 1.0 cm in the LPD, respectively) as assessed by CT or MRI * Participants must be willing to undergo an incisional, excisional, or core needle lymph node or tissue biopsy or provide a lymph node or tissue biopsy collected after the completion of last therapy. An earlier archived lymph node or tissue biopsy is acceptable if hospitalization is required for biopsy (eg. no superficial lymph node) and SUVmax by FDG-PET is \< 14 * ECOG performance status 0 to 2 * Life expectancy ≥ 12 weeks * Adequate hematologic, hepatic, and renal functions ANC ≥ 1.0 × 109/L Hemoglobin ≥ 8.0 g/dL. Platelet count ≥ 50 × 109/L. Total bilirubin ≤ 1.5 × ULN. Participants with documented history of Gilbert's syndrome and in whom total bilirubin elevations are accompanied by elevated indirect bilirubin are eligible. ALT/AST ≤ 2.5× ULN or ≤ 5 × ULN in the presence of liver involvement. Calculated creatinine clearance ≥ 40 mL/min by the Cockcroft-Gault Equation or the estimated glomerular filtration rate ≥ 40 mL/min/1.73 m2 using the Modification of Diet in Renal Disease formula. * Female participants agree to use medically acceptable contraceptive measures, should not be breastfeeding, and must have a negative pregnancy test before the start of study drug administration. * Female participants of childbearing potential must understand and accept that pregnancy must be avoided during participation in the study. * Male participants should avoid fathering children from screening through at least 93 days after the last dose of study treatment.
Exclusion criteria
* Known histological transformation from indolent NHL to DLBCL * History of central nervous system lymphoma (either primary or metastatic) * Prior treatment with the following: 1. Selective PI3Kδ or pan-PI3K inhibitors (eg, idelalisib, copanlisib, duvelisib, etc). 2. Bruton's tyrosine kinase inhibitor (eg, ibrutinib). * Allogeneic SCT within the last 6 months, or autologous SCT within the last 3 months before the date of study treatment administration * Active graft-versus-host disease * Use of immunosuppressive therapy within 28 days of the date of study treatment administration * Concurrent anticancer therapy * Significant concurrent, uncontrolled medical condition including, but not limited to, renal, hepatic, hematological, gastrointestinal, endocrine, pulmonary, neurological, cerebral, or psychiatric disease * Current or previous other malignancy within 3 years of study entry, except cured basal or squamous cell skin cancer, superficial bladder cancer, prostate intraepithelial neoplasm, carcinoma in situ of the cervix, or other noninvasive or indolent malignancy without sponsor approval. * Hepatitis B (HBV) or HCV infection * Current New York Heart Association Class II to IV congestive heart failure or uncontrolled arrhythmia
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) | up to approximately 3 years | ORR was defined as the percentage of participants with a complete response (CR) or partial response (PR) as defined by revised response criteria for lymphoma, as determined by an Independent Review Committee (IRC). CR: target nodes/nodal masses regressed to ≤1.5 centimeters (cm) in the longest transverse diameter (LDi); no nonmeasured lesions; regression to normal for organ enlargement; no new lesions; and normal bone marrow by morphology and negative immunohistochemistry if indeterminate. PR: ≥50% decrease in sum of the product of the diameters (SPD) of up to 6 target measurable nodes and extranodal sites; absent/regressed nonmeasured lesions (but no increase); spleen regressed by \>50% in length beyond normal; and no new lesions. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Response (DOR) | up to 20.0 months | DOR was defined as the time from the first documented evidence of CR or PR until disease progression or death from any cause among participants who achieved an objective response, as determined by radiographic disease assessment provided by an IRC. Progressive disease was defined as ≥1 of the following: abnormal individual node/lesion meeting specific criteria; new/recurrent splenomegaly; new/clear progression of pre-existing nonmeasured lesions; regrowth of any previously resolved lesions; new node \>1.5 cm in any axis; new extranodal site \>1.0 cm in any axis; assessable disease of any size attributable to lymphoma; new/recurrent involvement of bone marrow. |
| Progression-free Survival (PFS) | up to approximately 3 years | 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. Progressive disease was defined as any new lesion or increase by ≥ 50% of previously involved sites from nadir. |
| Overall Survival | up to approximately 3 years | Overall survival was defined as the time from the date of the first dose of study treatment until death from any cause. |
| Complete Response Rate (CRR) | up to approximately 3 years | CRR was defined as the percentage of participants with a CR as defined by revised response criteria for lymphoma, as determined by an IRC. CR was defined as: target nodes/nodal masses regressed to ≤1.5 cm in the LDi; no nonmeasured lesions; regression to normal for organ enlargement; no new lesions; and normal bone marrow by morphology and negative immunohistochemistry if indeterminate. |
| Number of Participants With Any Treatment-emergent Adverse Event (TEAE) | up to 1041 days | An adverse event was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug-related. An AE could therefore have been any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study treatment. A TEAE was defined as any AE either reported for the first time or the worsening of a pre-existing event after the first dose of study drug and within 30 days of the last administration of study drug. |
| Number of Participants With Any Grade 3 or Higher TEAE | up to 1041 days | An adverse event was as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug-related. A TEAE was defined as any AE either reported for the first time or the worsening of a pre-existing event after the first dose of study drug and within 30 days of the last administration of study drug. The severity of AEs was assessed using Common Terminology Criteria for Adverse Events (CTCAE) v5.0. Grade 1: mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; treatment not indicated. Grade 2: moderate; minimal, local, or noninvasive treatment indicated; limiting age appropriate activities of daily living. Grade 3: severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care activities of daily living. Grade 4: life-threatening consequences; urgent treatment indicated. Grade 5: fatal. |
| Best Percentage Change in Target Lesion Size From Baseline, as Determined by Independent Review Committee and the Investigator | up to approximately 3 years | Target lesion size was measured by the sum of the products of the diameters of all target lesion sizes. The best percent change from Baseline was defined as the largest decrease, or smallest increase if no decrease, from Baseline in target lesion sizes on/before new anti-lymphoma therapy during the study. Percentage change was calculated as (\[the post-Baseline value minus the Baseline value\] / the Baseline value) x 100. |
Countries
Japan
Participant flow
Pre-assignment details
This study was conducted at 19 study centers in Japan.
Participants by arm
| Arm | Count |
|---|---|
| Parsaclisib 20 mg/2.5 mg Participants received parsaclisib 20 milligrams (mg) once daily for 8 weeks, followed by 2.5 mg once daily, continuously. Participants received treatment until disease progression, death, hematopoietic stem cell transplantation (HSCT) (if eligible), unacceptable toxicity, or consent withdrawal. | 42 |
| Total | 42 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 4 |
| Overall Study | Progressive Disease | 18 |
| Overall Study | Transitioned to Rollover Study | 19 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Parsaclisib 20 mg/2.5 mg |
|---|---|
| Age, Continuous | 67.5 years STANDARD_DEVIATION 7.81 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 42 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 0 Participants |
| Sex: Female, Male Female | 20 Participants |
| Sex: Female, Male Male | 22 Participants |
| Target lesion size, as determined by Independent Review Committee and the Investigator Independent Review Committee | 2210.12 millimeters squared (mm^2) STANDARD_DEVIATION 1456.044 |
| Target lesion size, as determined by Independent Review Committee and the Investigator Investigator | 2487.24 millimeters squared (mm^2) STANDARD_DEVIATION 2197.143 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 4 / 42 | 4 / 42 |
| other Total, other adverse events | 38 / 42 | 38 / 42 |
| serious Total, serious adverse events | 15 / 42 | 15 / 42 |
Outcome results
Primary
Objective Response Rate (ORR)
ORR was defined as the percentage of participants with a complete response (CR) or partial response (PR) as defined by revised response criteria for lymphoma, as determined by an Independent Review Committee (IRC). CR: target nodes/nodal masses regressed to ≤1.5 centimeters (cm) in the longest transverse diameter (LDi); no nonmeasured lesions; regression to normal for organ enlargement; no new lesions; and normal bone marrow by morphology and negative immunohistochemistry if indeterminate. PR: ≥50% decrease in sum of the product of the diameters (SPD) of up to 6 target measurable nodes and extranodal sites; absent/regressed nonmeasured lesions (but no increase); spleen regressed by \>50% in length beyond normal; and no new lesions.
Time frame: up to approximately 3 years
Population: Full Analysis Set: all participants enrolled in the study who received at least 1 dose of parsaclisib. Confidence intervals were calculated based on the exact method for binomial distributions.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Parsaclisib 20 mg/2.5 mg | Objective Response Rate (ORR) | 88.1 percentage of participants |
Secondary
Best Percentage Change in Target Lesion Size From Baseline, as Determined by Independent Review Committee and the Investigator
Target lesion size was measured by the sum of the products of the diameters of all target lesion sizes. The best percent change from Baseline was defined as the largest decrease, or smallest increase if no decrease, from Baseline in target lesion sizes on/before new anti-lymphoma therapy during the study. Percentage change was calculated as (\[the post-Baseline value minus the Baseline value\] / the Baseline value) x 100.
Time frame: up to approximately 3 years
Population: Full Analysis Set. Only participants with available data (who had measurable regions) were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Parsaclisib 20 mg/2.5 mg | Best Percentage Change in Target Lesion Size From Baseline, as Determined by Independent Review Committee and the Investigator | Investigator | -79.31 percent change | Standard Deviation 23.181 |
| Parsaclisib 20 mg/2.5 mg | Best Percentage Change in Target Lesion Size From Baseline, as Determined by Independent Review Committee and the Investigator | Independent Review Committee | -67.26 percent change | Standard Deviation 39.897 |
Secondary
Complete Response Rate (CRR)
CRR was defined as the percentage of participants with a CR as defined by revised response criteria for lymphoma, as determined by an IRC. CR was defined as: target nodes/nodal masses regressed to ≤1.5 cm in the LDi; no nonmeasured lesions; regression to normal for organ enlargement; no new lesions; and normal bone marrow by morphology and negative immunohistochemistry if indeterminate.
Time frame: up to approximately 3 years
Population: Full Analysis Set. Confidence intervals were calculated based on the exact method for binomial distributions.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Parsaclisib 20 mg/2.5 mg | Complete Response Rate (CRR) | 23.8 percentage of participants |
Secondary
Duration of Response (DOR)
DOR was defined as the time from the first documented evidence of CR or PR until disease progression or death from any cause among participants who achieved an objective response, as determined by radiographic disease assessment provided by an IRC. Progressive disease was defined as ≥1 of the following: abnormal individual node/lesion meeting specific criteria; new/recurrent splenomegaly; new/clear progression of pre-existing nonmeasured lesions; regrowth of any previously resolved lesions; new node \>1.5 cm in any axis; new extranodal site \>1.0 cm in any axis; assessable disease of any size attributable to lymphoma; new/recurrent involvement of bone marrow.
Time frame: up to 20.0 months
Population: Full Analysis Set. Only participants with a CR or PR were analyzed. The 95% confidence interval was calculated using the generalization of Brookmeyer and Crowley's method with log-log transformation.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Parsaclisib 20 mg/2.5 mg | Duration of Response (DOR) | NA months |
Secondary
Number of Participants With Any Grade 3 or Higher TEAE
An adverse event was as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug-related. A TEAE was defined as any AE either reported for the first time or the worsening of a pre-existing event after the first dose of study drug and within 30 days of the last administration of study drug. The severity of AEs was assessed using Common Terminology Criteria for Adverse Events (CTCAE) v5.0. Grade 1: mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; treatment not indicated. Grade 2: moderate; minimal, local, or noninvasive treatment indicated; limiting age appropriate activities of daily living. Grade 3: severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care activities of daily living. Grade 4: life-threatening consequences; urgent treatment indicated. Grade 5: fatal.
Time frame: up to 1041 days
Population: Safety Population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Parsaclisib 20 mg/2.5 mg | Number of Participants With Any Grade 3 or Higher TEAE | 28 Participants |
Secondary
Number of Participants With Any Treatment-emergent Adverse Event (TEAE)
An adverse event was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug-related. An AE could therefore have been any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study treatment. A TEAE was defined as any AE either reported for the first time or the worsening of a pre-existing event after the first dose of study drug and within 30 days of the last administration of study drug.
Time frame: up to 1041 days
Population: Safety Population: all enrolled participants who received at least 1 dose of parsaclisib
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Parsaclisib 20 mg/2.5 mg | Number of Participants With Any Treatment-emergent Adverse Event (TEAE) | 42 Participants |
Secondary
Overall Survival
Overall survival was defined as the time from the date of the first dose of study treatment until death from any cause.
Time frame: up to approximately 3 years
Population: Full Analysis Set. The 95% confidence interval was calculated using the generalization of Brookmeyer and Crowley's method with log-log transformation.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Parsaclisib 20 mg/2.5 mg | Overall Survival | NA months |
Secondary
Progression-free Survival (PFS)
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. Progressive disease was defined as any new lesion or increase by ≥ 50% of previously involved sites from nadir.
Time frame: up to approximately 3 years
Population: Fully Analysis Set. The 95% confidence interval was calculated using the generalization of Brookmeyer and Crowley's method with log-log transformation.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Parsaclisib 20 mg/2.5 mg | Progression-free Survival (PFS) | NA months |