Cutaneous T-cell Lymphoma, Peripheral T-cell Lymphoma
Conditions
Keywords
Peripheral T-cell lymphoma, Cutaneous T-cell lymphoma, E7777, Phase 2
Brief summary
The purpose of this study is to evaluate the objective response rate (ORR) of E7777 in participants with relapsed or refractory peripheral T-cell lymphoma (PTCL) and cutaneous T-cell lymphoma (CTCL).
Detailed description
This is a multicenter, single-arm, open label, Phase 2 to evaluate efficacy, safety, pharmacokinetics and immunogenicity of E7777 in participants with relapsed or refractory PTCL and CTCL.
Interventions
DRUGE7777
Sponsors
Eisai Co., Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Participants who have histological diagnosis as peripheral T-cell lymphoma (PTCL) and cutaneous T-cell lymphoma (CTCL). 2. Participant who have measurable disease. 3. Participant who had previous systemic chemotherapy. 4. Participant who had disease progression (PD) or did not have response (complete response (CR) or partial response (PR)) in systemic chemotherapy, or relapsed or progressed after systemic chemotherapy. 5. Participant with Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0 or 1. 6. Participant with adequate renal, liver and bone marrow function. 7. Male and female participants ≥20 years of age at the time of informed consent. 8. Participants who have provided written consent to participate in the study.
Exclusion criteria
1. Participant with serious complications or histories. 2. Participant with history of hypersensitivity to protein therapeutics. 3. Participant who is positive for Human immunodeficiency virus (HIV) antibody, Hepatitis C virus (HCV) antibody, or Hepatitis B Surface (HBs) antigen. 4. Participant with malignancy of activity other than PTCL or CTCL within 36 months before informed consent. 5. Women of childbearing potential or man of impregnate potential who don't agree to use a medically effective method for contraception. 6. Woman who is pregnant or lactating. 7. Participant with allogeneic stem cell transplantation. 8. Participant who were decided as inappropriate to participate in the study by the investigator or sub-investigator.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) | From the date of administration of the first dose of the study drug until completion of the study or treatment discontinuation, up to approximately 3 years 1 month | ORR was defined as the percentage of participants whose best overall response (BOR) was complete response (CR) or partial response (PR) based on independent review of Efficacy and Safety Evaluation Committee. ORR was assessed according to modified response criteria based on the revised response criteria for malignant lymphoma (Cheson, 2007), skin lesion and peripheral blood disease were assessed according to clinical end points and response criteria in mycosis fungoides and Sezary syndrome (Olsen, 2011). CR: Disappearance of all evidence of disease; PR: Regression of measurable disease and no new sites. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Response (DOR) | From the date of first documentation of CR or PR until date of the first documentation of PD or death due to any cause (whichever occurred first) up to approximately 3 years 1 month | DOR: Time between date of first documentation of CR or PR and PD or death due to any cause based on independent review of Efficacy and Safety Evaluation Committee, assessed by modified response criteria based on revised response criteria for malignant lymphoma (Cheson,2007),skin lesion and peripheral blood disease by clinical end points and response criteria in mycosis fungoides and Sezary syndrome(Olsen,2011). DOR was assessed in responders who had CR or PR. CR: Disappearance of all evidence of disease; PR: Regression of measurable disease and no new sites. PD: Any new lesion or unequivocally increase of previously involved sites from nadir. DOR was calculated using Kaplan-Meier method. Participants with new anticancer treatment started prior to disease progression, death or PD after more than one missed tumor assessments and participants still on treatment without PD as of data cut-off were censored. |
| Time to Response (TTR) | From the date of administration of the first dose of the study drug until date of the first documentation of PR or CR or death due to any cause (whichever occurred first) up to approximately 3 years 1 month | TTR was defined as time between the date of administration of the first dose of the study drug and the date of first documentation PR or CR based on independent review of Efficacy and Safety Evaluation Committee. PR or CR were assessed according to modified response criteria based on the revised response criteria for malignant lymphoma (Cheson, 2007), skin lesion and peripheral blood disease were assessed according to clinical end points and response criteria in mycosis fungoides and Sezary syndrome (Olsen, 2011). TTR was only conducted among responders who had experienced CR or PR. CR: Disappearance of all evidence of disease; PR: Regression of measurable disease and no new sites. |
| CR Rate | From the date of administration of the first dose of the study drug until completion of the study or treatment discontinuation, up to approximately 3 years 1 month | CR rate was defined as the percentage of participants whose BOR was CR based on independent review of Efficacy and Safety Evaluation Committee. CR was assessed according to modified response criteria based on the revised response criteria for malignant lymphoma (Cheson, 2007), skin lesion and peripheral blood disease were assessed according to clinical end points and response criteria in mycosis fungoides and Sezary syndrome (Olsen, 2011). CR: Disappearance of all evidence of disease. |
| Overall Survival (OS) | From date of administration of the first dose of the study drug until the date of death due to any cause up to approximately 3 years 1 month | OS was defined as the time between the date of administration of the first dose of the study drug and the date of death due to any cause. Participants who were alive at cut-off were censored. |
| Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | From the date of administration of the first dose of the study drug up to 30 days after the last dose of study drug (approximately up to 3 years 1 month) | — |
| Cmax: Maximum Observed Serum Concentration for E7777 | Cycle 1 Day 1: 0-240 minutes post-infusion; Cycle 3 and 5 Day 1: 0-120 minutes post-infusion (each Cycle length = 3 weeks) | — |
| Tmax: Time to Reach the Cmax for E7777 | Cycle 1 Day 1: 0-240 minutes post-infusion; Cycle 3 and 5 Day 1: 0-120 minutes post-infusion (each Cycle length = 3 weeks) | — |
| AUC(0-t ): Area Under the Serum Concentration-time Curve From Time 0 to the Last Measurable Point for E7777 | Cycle 1 Day 1: 0-240 minutes post-infusion; Cycle 3 and 5 Day 1: 0-120 minutes post-infusion (each Cycle length = 3 weeks) | — |
| AUC(0-inf): Area Under the Serum Concentration-time Curve From Time 0 to Infinity for E7777 | Cycle 1 Day 1: 0-240 minutes post-infusion; Cycle 3 and 5 Day 1: 0-120 minutes post-infusion (each Cycle length = 3 weeks) | 11 participants were included in the PK analysis, however AUC(0-inf), could not be estimated for 1 participant due to insufficient data for elimination rate constant. |
| Progression Free Survival (PFS) | From the date of administration of the first dose of the study drug until date of the first documentation of PD or death due to any cause (whichever occurred first) up to approximately 3 years 1 month | PFS: time between the date of administration of the first dose of the study drug and the date of the first documentation of progressive disease (PD) or death due to any cause (whichever occurred first) based on independent review of Efficacy and Safety Evaluation Committee, assessed by modified response criteria based on the revised response criteria for malignant lymphoma (Cheson, 2007), skin lesion and peripheral blood disease assessed according to clinical end points and response criteria in mycosis fungoides and Sezary syndrome (Olsen, 2011). PD: Any new lesion or unequivocally increase of previously involved sites from nadir. PFS was calculated using Kaplan-Meier method. Participants with no baseline assessments, treatment discontinuation without postbaseline tumor assessments, new anticancer treatment started prior to disease progression, death or PD after more than one missed tumor assessments and participants still on treatment without PD as of data cut-off were censored. |
| t1/2: Terminal Elimination Phase Half-life for E7777 | Cycle 1 Day 1: 0-240 minutes post-infusion; Cycle 3 and 5 Day 1: 0-120 minutes post-infusion (each Cycle length = 3 weeks) | 11 participants were included in the PK analysis, however t1/2, could not be estimated for 1 participant due to insufficient data for elimination rate constant. |
| CL: Total Clearance for E7777 | Cycle 1 Day 1: 0-240 minutes post-infusion; Cycle 3 and 5 Day 1: 0-120 minutes post-infusion (each Cycle length = 3 weeks) | 11 participants were included in the PK analysis, however CL, could not be estimated for 1 participant due to insufficient data for elimination rate constant. |
| Vz: Volume of Distribution at Terminal Phase for E7777 | Cycle 1 Day 1: 0-240 minutes post-infusion; Cycle 3 and 5 Day 1: 0-120 minutes post-infusion (each Cycle length = 3 weeks) | 11 participants were included in the PK analysis, however Vz, could not be estimated for 1 participant due to insufficient data for elimination rate constant. |
| Vss: Volume of Distribution at Steady State for E7777 | Cycle 1 Day 1: 0-240 minutes post-infusion; Cycle 3 and 5 Day 1: 0-120 minutes post-infusion (each Cycle length = 3 weeks) | 11 participants were included in the PK analysis, however Vss, could not be estimated for 1 participant due to insufficient data for elimination rate constant. |
| Rac (Cmax): Accumulation Ratio of Cmax for E7777 | Cycle 1 Day 1: 0-240 minutes post-infusion; Cycle 3 and 5 Day 1: 0-120 minutes post-infusion (each Cycle length = 3 weeks) | Accumulation Ratio of Cmax was calculated as RAC (Cmax) on Cycle 3 Day 1 divided by RAC (Cmax) on Cycle 1 Day 1, and RAC (Cmax) on Cycle 5 Day 1 divided by RAC (Cmax) on Cycle 1 Day 1. |
| Rac (AUC): Accumulation Ratio of AUC for E7777 | Cycle 1 Day 1: 0-240 minutes post-infusion; Cycle 3 and 5 Day 1: 0-120 minutes post-infusion (each Cycle length = 3 weeks) | Accumulation ratio of AUC was calculated as RAC (AUC) on Cycle 3 Day 1 divided by RAC (AUC) on Cycle 1 Day 1, and RAC (AUC) on Cycle 5 Day 1 divided by RAC (AUC) on Cycle 1 Day 1. |
| Number of Participants With Positive Anti-E7777 and Anti-IL-2 Antibodies | Cycles 1, 2, 3, 5, 8: Day 1 pre-dose; at treatment discontinuation or completion (Cycle 8 Day 21) (each Cycle length = 3 weeks) | — |
| Number of Participants With Positive Neutralizing Activity of Anti-E7777 Antibody | Cycles 1, 2, 3, 5, 8: Day 1 pre-dose; at treatment discontinuation or completion (Cycle 8 Day 21) (each Cycle length = 3 weeks) | — |
| Mean Residence Time (MRT) for E7777 | Cycle 1 Day 1: 0-240 minutes post-infusion; Cycle 3 and 5 Day 1: 0-120 minutes post-infusion (each Cycle length = 3 weeks) | 11 participants were included in the PK analysis, however MRT, could not be estimated for 1 participant due to insufficient data for elimination rate constant. |
Countries
Japan
Participant flow
Recruitment details
Participants took part in the study at 20 investigative sites in Japan from 28 March 2016 to 26 April 2019.
Pre-assignment details
A total of 45 participants were enrolled (obtained informed consent and screened), of these 8 were screen failures and 37 were treated.
Participants by arm
| Arm | Count |
|---|---|
| PTCL: E7777 9 mcg/kg/Day Participants with relapsed or refractory PTCL received E7777 9 mcg/kg/day as intravenous infusion, once daily from Day 1 through Day 5 in each treatment cycle until discontinuation or Cycle 8 (each Cycle length = 3 weeks). | 17 |
| CTCL: E7777 9 mcg/kg/Day Participants with CTCL received E7777 9 mcg/kg/day as intravenous infusion, once daily from Day 1 through Day 5 in each treatment cycle until discontinuation or Cycle 8 (each Cycle length = 3 weeks). | 19 |
| Other: E7777 9 mcg/kg/Day Participant with extranodal NK/T-cell lymphoma received E7777 9 mcg/kg/day as intravenous infusion, once daily from Day 1 through Day 5 in each treatment cycle until discontinuation or Cycle 8 (each Cycle length = 3 weeks). | 1 |
| Total | 37 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 2 | 3 | 0 |
| Overall Study | Couldn't Start Cycle After Planned Date | 1 | 1 | 0 |
| Overall Study | Disease Progression | 7 | 3 | 1 |
| Overall Study | Other | 4 | 3 | 0 |
| Overall Study | Withdrawal by Subject | 3 | 2 | 0 |
Baseline characteristics
| Characteristic | PTCL: E7777 9 mcg/kg/Day | CTCL: E7777 9 mcg/kg/Day | Other: E7777 9 mcg/kg/Day | Total |
|---|---|---|---|---|
| Age, Continuous | 66.7 years STANDARD_DEVIATION 9.16 | 55.3 years STANDARD_DEVIATION 15.09 | 70.0 years | 60.9 years STANDARD_DEVIATION 13.63 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 17 Participants | 19 Participants | 1 Participants | 37 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Japanese | 17 Participants | 19 Participants | 1 Participants | 37 Participants |
| Sex: Female, Male Female | 5 Participants | 6 Participants | 1 Participants | 12 Participants |
| Sex: Female, Male Male | 12 Participants | 13 Participants | 0 Participants | 25 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 17 | 1 / 19 | 0 / 1 |
| other Total, other adverse events | 17 / 17 | 19 / 19 | 1 / 1 |
| serious Total, serious adverse events | 9 / 17 | 8 / 19 | 0 / 1 |
Outcome results
Primary
Objective Response Rate (ORR)
ORR was defined as the percentage of participants whose best overall response (BOR) was complete response (CR) or partial response (PR) based on independent review of Efficacy and Safety Evaluation Committee. ORR was assessed according to modified response criteria based on the revised response criteria for malignant lymphoma (Cheson, 2007), skin lesion and peripheral blood disease were assessed according to clinical end points and response criteria in mycosis fungoides and Sezary syndrome (Olsen, 2011). CR: Disappearance of all evidence of disease; PR: Regression of measurable disease and no new sites.
Time frame: From the date of administration of the first dose of the study drug until completion of the study or treatment discontinuation, up to approximately 3 years 1 month
Population: The full analysis set (FAS) was defined as a group of participants who received at least 1 dose of the study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PTCL: E7777 9 mcg/kg/Day | Objective Response Rate (ORR) | 41.2 percentage of participants |
| CTCL: E7777 9 mcg/kg/Day | Objective Response Rate (ORR) | 31.6 percentage of participants |
Secondary
AUC(0-inf): Area Under the Serum Concentration-time Curve From Time 0 to Infinity for E7777
11 participants were included in the PK analysis, however AUC(0-inf), could not be estimated for 1 participant due to insufficient data for elimination rate constant.
Time frame: Cycle 1 Day 1: 0-240 minutes post-infusion; Cycle 3 and 5 Day 1: 0-120 minutes post-infusion (each Cycle length = 3 weeks)
Population: The PK analysis set was defined as a group of participants who received at least 1 dose of the study drug with at least 1 serum concentration data, and included participants who had been taken frequent blood sampling for non-compartment analysis. PK-evaluable population where data at specified time points was available.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PTCL: E7777 9 mcg/kg/Day | AUC(0-inf): Area Under the Serum Concentration-time Curve From Time 0 to Infinity for E7777 | Cycle 1 Day 1 | 23000 ng*min/m | Standard Deviation 7830 |
| PTCL: E7777 9 mcg/kg/Day | AUC(0-inf): Area Under the Serum Concentration-time Curve From Time 0 to Infinity for E7777 | Cycle 5 Day 1 | 21400 ng*min/m | — |
Secondary
AUC(0-t ): Area Under the Serum Concentration-time Curve From Time 0 to the Last Measurable Point for E7777
Time frame: Cycle 1 Day 1: 0-240 minutes post-infusion; Cycle 3 and 5 Day 1: 0-120 minutes post-infusion (each Cycle length = 3 weeks)
Population: The PK analysis set was defined as a group of participants who received at least 1 dose of the study drug with at least 1 serum concentration data, and included participants who had been taken frequent blood sampling for non-compartment analysis. PK-evaluable population where data at specified time points was available.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PTCL: E7777 9 mcg/kg/Day | AUC(0-t ): Area Under the Serum Concentration-time Curve From Time 0 to the Last Measurable Point for E7777 | Cycle 3 Day 1 | 15800 nanogram*minute permilliliter(ng*min/mL) | — |
| PTCL: E7777 9 mcg/kg/Day | AUC(0-t ): Area Under the Serum Concentration-time Curve From Time 0 to the Last Measurable Point for E7777 | Cycle 5 Day 1 | 16500 nanogram*minute permilliliter(ng*min/mL) | — |
| PTCL: E7777 9 mcg/kg/Day | AUC(0-t ): Area Under the Serum Concentration-time Curve From Time 0 to the Last Measurable Point for E7777 | Cycle 1 Day 1 | 17600 nanogram*minute permilliliter(ng*min/mL) | Standard Deviation 8040 |
Secondary
CL: Total Clearance for E7777
11 participants were included in the PK analysis, however CL, could not be estimated for 1 participant due to insufficient data for elimination rate constant.
Time frame: Cycle 1 Day 1: 0-240 minutes post-infusion; Cycle 3 and 5 Day 1: 0-120 minutes post-infusion (each Cycle length = 3 weeks)
Population: The PK analysis set was defined as a group of participants who received at least 1 dose of the study drug with at least 1 serum concentration data, and included participants who had been taken frequent blood sampling for non-compartment analysis. PK-evaluable population where data at specified time points was available.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PTCL: E7777 9 mcg/kg/Day | CL: Total Clearance for E7777 | Cycle 1 Day 1 | 0.465 milliter per minute per kilogram | Standard Deviation 0.25 |
| PTCL: E7777 9 mcg/kg/Day | CL: Total Clearance for E7777 | Cycle 5 Day 1 | 0.421 milliter per minute per kilogram | — |
Secondary
Cmax: Maximum Observed Serum Concentration for E7777
Time frame: Cycle 1 Day 1: 0-240 minutes post-infusion; Cycle 3 and 5 Day 1: 0-120 minutes post-infusion (each Cycle length = 3 weeks)
Population: The pharmacokinetic (PK) analysis set was defined as a group of participants who received at least 1 dose of the study drug with at least 1 serum concentration data, and included participants who had been taken frequent blood sampling for non-compartment analysis. PK-evaluable population where data at specified time points was available.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PTCL: E7777 9 mcg/kg/Day | Cmax: Maximum Observed Serum Concentration for E7777 | Cycle 1 Day 1 | 132 nanogram per milliliter (ng/mL) | Standard Deviation 43.1 |
| PTCL: E7777 9 mcg/kg/Day | Cmax: Maximum Observed Serum Concentration for E7777 | Cycle 3 Day 1 | 142 nanogram per milliliter (ng/mL) | — |
| PTCL: E7777 9 mcg/kg/Day | Cmax: Maximum Observed Serum Concentration for E7777 | Cycle 5 Day 1 | 140 nanogram per milliliter (ng/mL) | — |
Secondary
CR Rate
CR rate was defined as the percentage of participants whose BOR was CR based on independent review of Efficacy and Safety Evaluation Committee. CR was assessed according to modified response criteria based on the revised response criteria for malignant lymphoma (Cheson, 2007), skin lesion and peripheral blood disease were assessed according to clinical end points and response criteria in mycosis fungoides and Sezary syndrome (Olsen, 2011). CR: Disappearance of all evidence of disease.
Time frame: From the date of administration of the first dose of the study drug until completion of the study or treatment discontinuation, up to approximately 3 years 1 month
Population: The FAS was defined as a group of participants who received at least 1 dose of the study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PTCL: E7777 9 mcg/kg/Day | CR Rate | 5.9 percentage of participants |
| CTCL: E7777 9 mcg/kg/Day | CR Rate | 0 percentage of participants |
Secondary
Duration of Response (DOR)
DOR: Time between date of first documentation of CR or PR and PD or death due to any cause based on independent review of Efficacy and Safety Evaluation Committee, assessed by modified response criteria based on revised response criteria for malignant lymphoma (Cheson,2007),skin lesion and peripheral blood disease by clinical end points and response criteria in mycosis fungoides and Sezary syndrome(Olsen,2011). DOR was assessed in responders who had CR or PR. CR: Disappearance of all evidence of disease; PR: Regression of measurable disease and no new sites. PD: Any new lesion or unequivocally increase of previously involved sites from nadir. DOR was calculated using Kaplan-Meier method. Participants with new anticancer treatment started prior to disease progression, death or PD after more than one missed tumor assessments and participants still on treatment without PD as of data cut-off were censored.
Time frame: From the date of first documentation of CR or PR until date of the first documentation of PD or death due to any cause (whichever occurred first) up to approximately 3 years 1 month
Population: The FAS was defined as a group of participants who received at least 1 dose of the study drug. Here overall number of participants analyzed signifies responded participants.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| PTCL: E7777 9 mcg/kg/Day | Duration of Response (DOR) | 3.09 months |
| CTCL: E7777 9 mcg/kg/Day | Duration of Response (DOR) | 4.83 months |
Secondary
Mean Residence Time (MRT) for E7777
11 participants were included in the PK analysis, however MRT, could not be estimated for 1 participant due to insufficient data for elimination rate constant.
Time frame: Cycle 1 Day 1: 0-240 minutes post-infusion; Cycle 3 and 5 Day 1: 0-120 minutes post-infusion (each Cycle length = 3 weeks)
Population: The PK analysis set was defined as a group of participants who received at least 1 dose of the study drug with at least 1 serum concentration data, and included participants who had been taken frequent blood sampling for non-compartment analysis. PK-evaluable population where data at specified time points was available.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PTCL: E7777 9 mcg/kg/Day | Mean Residence Time (MRT) for E7777 | Cycle 1 Day 1 | 136 minutes | Standard Deviation 29.2 |
| PTCL: E7777 9 mcg/kg/Day | Mean Residence Time (MRT) for E7777 | Cycle 5 Day 1 | 105 minutes | — |
Secondary
Number of Participants With Positive Anti-E7777 and Anti-IL-2 Antibodies
Time frame: Cycles 1, 2, 3, 5, 8: Day 1 pre-dose; at treatment discontinuation or completion (Cycle 8 Day 21) (each Cycle length = 3 weeks)
Population: The pharmacodynamics (PD) analysis set was defined as a group of participants who received at least 1 dose of the study drug with at least 1 each of evaluable pre- and post-baseline PD data. Participants who were evaluable for this measure at given time point were included for the assessment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| PTCL: E7777 9 mcg/kg/Day | Number of Participants With Positive Anti-E7777 and Anti-IL-2 Antibodies | Anti-E7777 antibody: Cycle 1 Day 1 | 11 Participants |
| PTCL: E7777 9 mcg/kg/Day | Number of Participants With Positive Anti-E7777 and Anti-IL-2 Antibodies | Anti-E7777 antibody: Cycle 2 Day 1 | 5 Participants |
| PTCL: E7777 9 mcg/kg/Day | Number of Participants With Positive Anti-E7777 and Anti-IL-2 Antibodies | Anti-E7777 antibody: Cycle 3 Day 1 | 3 Participants |
| PTCL: E7777 9 mcg/kg/Day | Number of Participants With Positive Anti-E7777 and Anti-IL-2 Antibodies | Anti-E7777 antibody: Cycle 5 Day 1 | 1 Participants |
| PTCL: E7777 9 mcg/kg/Day | Number of Participants With Positive Anti-E7777 and Anti-IL-2 Antibodies | Anti-E7777 antibody: Discontinuation/Completion | 10 Participants |
| PTCL: E7777 9 mcg/kg/Day | Number of Participants With Positive Anti-E7777 and Anti-IL-2 Antibodies | Anti-IL-2 antibody: Cycle 1 Day 1 | 1 Participants |
| PTCL: E7777 9 mcg/kg/Day | Number of Participants With Positive Anti-E7777 and Anti-IL-2 Antibodies | Anti-IL-2 antibody: Cycle 2 Day 1 | 2 Participants |
| PTCL: E7777 9 mcg/kg/Day | Number of Participants With Positive Anti-E7777 and Anti-IL-2 Antibodies | Anti-IL-2 antibody: Cycle 3 Day 1 | 2 Participants |
| PTCL: E7777 9 mcg/kg/Day | Number of Participants With Positive Anti-E7777 and Anti-IL-2 Antibodies | Anti-IL-2 antibody: Cycle 5 Day 1 | 1 Participants |
| PTCL: E7777 9 mcg/kg/Day | Number of Participants With Positive Anti-E7777 and Anti-IL-2 Antibodies | Anti-IL-2 antibody: Discontinuation/Completion | 3 Participants |
| CTCL: E7777 9 mcg/kg/Day | Number of Participants With Positive Anti-E7777 and Anti-IL-2 Antibodies | Anti-E7777 antibody: Cycle 5 Day 1 | 10 Participants |
| CTCL: E7777 9 mcg/kg/Day | Number of Participants With Positive Anti-E7777 and Anti-IL-2 Antibodies | Anti-IL-2 antibody: Discontinuation/Completion | 15 Participants |
| CTCL: E7777 9 mcg/kg/Day | Number of Participants With Positive Anti-E7777 and Anti-IL-2 Antibodies | Anti-E7777 antibody: Discontinuation/Completion | 15 Participants |
| CTCL: E7777 9 mcg/kg/Day | Number of Participants With Positive Anti-E7777 and Anti-IL-2 Antibodies | Anti-IL-2 antibody: Cycle 2 Day 1 | 4 Participants |
| CTCL: E7777 9 mcg/kg/Day | Number of Participants With Positive Anti-E7777 and Anti-IL-2 Antibodies | Anti-E7777 antibody: Cycle 1 Day 1 | 13 Participants |
| CTCL: E7777 9 mcg/kg/Day | Number of Participants With Positive Anti-E7777 and Anti-IL-2 Antibodies | Anti-E7777 antibody: Cycle 2 Day 1 | 11 Participants |
| CTCL: E7777 9 mcg/kg/Day | Number of Participants With Positive Anti-E7777 and Anti-IL-2 Antibodies | Anti-E7777 antibody: Cycle 3 Day 1 | 11 Participants |
| CTCL: E7777 9 mcg/kg/Day | Number of Participants With Positive Anti-E7777 and Anti-IL-2 Antibodies | Anti-IL-2 antibody: Cycle 3 Day 1 | 11 Participants |
| CTCL: E7777 9 mcg/kg/Day | Number of Participants With Positive Anti-E7777 and Anti-IL-2 Antibodies | Anti-E7777 antibody: Cycle 8 Day 1 | 7 Participants |
| CTCL: E7777 9 mcg/kg/Day | Number of Participants With Positive Anti-E7777 and Anti-IL-2 Antibodies | Anti-IL-2 antibody: Cycle 5 Day 1 | 10 Participants |
| CTCL: E7777 9 mcg/kg/Day | Number of Participants With Positive Anti-E7777 and Anti-IL-2 Antibodies | Anti-IL-2 antibody: Cycle 1 Day 1 | 1 Participants |
| CTCL: E7777 9 mcg/kg/Day | Number of Participants With Positive Anti-E7777 and Anti-IL-2 Antibodies | Anti-IL-2 antibody: Cycle 8 Day 1 | 7 Participants |
| Other: E7777 9 mcg/kg/Day | Number of Participants With Positive Anti-E7777 and Anti-IL-2 Antibodies | Anti-E7777 antibody: Discontinuation/Completion | 1 Participants |
| Other: E7777 9 mcg/kg/Day | Number of Participants With Positive Anti-E7777 and Anti-IL-2 Antibodies | Anti-E7777 antibody: Cycle 2 Day 1 | 0 Participants |
| Other: E7777 9 mcg/kg/Day | Number of Participants With Positive Anti-E7777 and Anti-IL-2 Antibodies | Anti-E7777 antibody: Cycle 1 Day 1 | 1 Participants |
| Other: E7777 9 mcg/kg/Day | Number of Participants With Positive Anti-E7777 and Anti-IL-2 Antibodies | Anti-IL-2 antibody: Cycle 1 Day 1 | 0 Participants |
| Other: E7777 9 mcg/kg/Day | Number of Participants With Positive Anti-E7777 and Anti-IL-2 Antibodies | Anti-IL-2 antibody: Cycle 2 Day 1 | 0 Participants |
| Other: E7777 9 mcg/kg/Day | Number of Participants With Positive Anti-E7777 and Anti-IL-2 Antibodies | Anti-IL-2 antibody: Discontinuation/Completion | 0 Participants |
Secondary
Number of Participants With Positive Neutralizing Activity of Anti-E7777 Antibody
Time frame: Cycles 1, 2, 3, 5, 8: Day 1 pre-dose; at treatment discontinuation or completion (Cycle 8 Day 21) (each Cycle length = 3 weeks)
Population: The PD analysis set was defined as a group of participants who received at least 1 dose of the study drug with at least 1 each of evaluable pre- and post-baseline PD data. Participants who were evaluable for this measure at given time point were included for the assessment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| PTCL: E7777 9 mcg/kg/Day | Number of Participants With Positive Neutralizing Activity of Anti-E7777 Antibody | Cycle 5 Day 1 | 1 Participants |
| PTCL: E7777 9 mcg/kg/Day | Number of Participants With Positive Neutralizing Activity of Anti-E7777 Antibody | Cycle 3 Day 1 | 2 Participants |
| PTCL: E7777 9 mcg/kg/Day | Number of Participants With Positive Neutralizing Activity of Anti-E7777 Antibody | Cycle 1 Day 1 | 0 Participants |
| PTCL: E7777 9 mcg/kg/Day | Number of Participants With Positive Neutralizing Activity of Anti-E7777 Antibody | Cycle 2 Day 1 | 2 Participants |
| PTCL: E7777 9 mcg/kg/Day | Number of Participants With Positive Neutralizing Activity of Anti-E7777 Antibody | Discontinuation/Completion | 8 Participants |
| CTCL: E7777 9 mcg/kg/Day | Number of Participants With Positive Neutralizing Activity of Anti-E7777 Antibody | Cycle 3 Day 1 | 11 Participants |
| CTCL: E7777 9 mcg/kg/Day | Number of Participants With Positive Neutralizing Activity of Anti-E7777 Antibody | Cycle 1 Day 1 | 0 Participants |
| CTCL: E7777 9 mcg/kg/Day | Number of Participants With Positive Neutralizing Activity of Anti-E7777 Antibody | Cycle 2 Day 1 | 9 Participants |
| CTCL: E7777 9 mcg/kg/Day | Number of Participants With Positive Neutralizing Activity of Anti-E7777 Antibody | Cycle 5 Day 1 | 8 Participants |
| CTCL: E7777 9 mcg/kg/Day | Number of Participants With Positive Neutralizing Activity of Anti-E7777 Antibody | Cycle 8 Day 1 | 6 Participants |
| CTCL: E7777 9 mcg/kg/Day | Number of Participants With Positive Neutralizing Activity of Anti-E7777 Antibody | Discontinuation/Completion | 12 Participants |
| Other: E7777 9 mcg/kg/Day | Number of Participants With Positive Neutralizing Activity of Anti-E7777 Antibody | Cycle 2 Day 1 | 0 Participants |
| Other: E7777 9 mcg/kg/Day | Number of Participants With Positive Neutralizing Activity of Anti-E7777 Antibody | Cycle 1 Day 1 | 0 Participants |
| Other: E7777 9 mcg/kg/Day | Number of Participants With Positive Neutralizing Activity of Anti-E7777 Antibody | Discontinuation/Completion | 0 Participants |
Secondary
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Time frame: From the date of administration of the first dose of the study drug up to 30 days after the last dose of study drug (approximately up to 3 years 1 month)
Population: The safety analysis set was defined as a group of participants who received at least 1 dose of the study drug with at least 1 evaluable postbaseline safety data.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| PTCL: E7777 9 mcg/kg/Day | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | TEAEs | 17 Participants |
| PTCL: E7777 9 mcg/kg/Day | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | SAEs | 9 Participants |
| CTCL: E7777 9 mcg/kg/Day | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | TEAEs | 19 Participants |
| CTCL: E7777 9 mcg/kg/Day | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | SAEs | 8 Participants |
| Other: E7777 9 mcg/kg/Day | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | TEAEs | 1 Participants |
| Other: E7777 9 mcg/kg/Day | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | SAEs | 0 Participants |
Secondary
Overall Survival (OS)
OS was defined as the time between the date of administration of the first dose of the study drug and the date of death due to any cause. Participants who were alive at cut-off were censored.
Time frame: From date of administration of the first dose of the study drug until the date of death due to any cause up to approximately 3 years 1 month
Population: The FAS was defined as a group of participants who received at least 1 dose of the study drug.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| PTCL: E7777 9 mcg/kg/Day | Overall Survival (OS) | 11.79 months |
| CTCL: E7777 9 mcg/kg/Day | Overall Survival (OS) | 31.87 months |
Secondary
Progression Free Survival (PFS)
PFS: time between the date of administration of the first dose of the study drug and the date of the first documentation of progressive disease (PD) or death due to any cause (whichever occurred first) based on independent review of Efficacy and Safety Evaluation Committee, assessed by modified response criteria based on the revised response criteria for malignant lymphoma (Cheson, 2007), skin lesion and peripheral blood disease assessed according to clinical end points and response criteria in mycosis fungoides and Sezary syndrome (Olsen, 2011). PD: Any new lesion or unequivocally increase of previously involved sites from nadir. PFS was calculated using Kaplan-Meier method. Participants with no baseline assessments, treatment discontinuation without postbaseline tumor assessments, new anticancer treatment started prior to disease progression, death or PD after more than one missed tumor assessments and participants still on treatment without PD as of data cut-off were censored.
Time frame: From the date of administration of the first dose of the study drug until date of the first documentation of PD or death due to any cause (whichever occurred first) up to approximately 3 years 1 month
Population: The FAS was defined as a group of participants who received at least 1 dose of the study drug.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| PTCL: E7777 9 mcg/kg/Day | Progression Free Survival (PFS) | 2.14 months |
| CTCL: E7777 9 mcg/kg/Day | Progression Free Survival (PFS) | 4.24 months |
Secondary
Rac (AUC): Accumulation Ratio of AUC for E7777
Accumulation ratio of AUC was calculated as RAC (AUC) on Cycle 3 Day 1 divided by RAC (AUC) on Cycle 1 Day 1, and RAC (AUC) on Cycle 5 Day 1 divided by RAC (AUC) on Cycle 1 Day 1.
Time frame: Cycle 1 Day 1: 0-240 minutes post-infusion; Cycle 3 and 5 Day 1: 0-120 minutes post-infusion (each Cycle length = 3 weeks)
Population: PK analysis set: group of participants who received at least 1 dose of study drug with at least 1 serum concentration data, and included participants who had taken frequent blood sampling for non-compartment analysis. Overall number of participants analyzed is number of participants with evaluable data at Cycle 1 Day 1 and at Cycles 3 and 5 Day 1
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| PTCL: E7777 9 mcg/kg/Day | Rac (AUC): Accumulation Ratio of AUC for E7777 | Cycle 5 Day 1 | 0.827 ratio |
| Unknown | Rac (AUC): Accumulation Ratio of AUC for E7777 | Cycle 3 Day 1 | — ratio |
Secondary
Rac (Cmax): Accumulation Ratio of Cmax for E7777
Accumulation Ratio of Cmax was calculated as RAC (Cmax) on Cycle 3 Day 1 divided by RAC (Cmax) on Cycle 1 Day 1, and RAC (Cmax) on Cycle 5 Day 1 divided by RAC (Cmax) on Cycle 1 Day 1.
Time frame: Cycle 1 Day 1: 0-240 minutes post-infusion; Cycle 3 and 5 Day 1: 0-120 minutes post-infusion (each Cycle length = 3 weeks)
Population: PK analysis set: group of participants who received at least 1 dose of study drug with at least 1 serum concentration data, and included participants who had taken frequent blood sampling for non-compartment analysis. Overall number of participants analyzed is number of participants with evaluable data at Cycle 1 Day 1 and at Cycles 3 and 5 Day 1
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| PTCL: E7777 9 mcg/kg/Day | Rac (Cmax): Accumulation Ratio of Cmax for E7777 | Cycle 3 Day 1 | 0.993 ratio |
| PTCL: E7777 9 mcg/kg/Day | Rac (Cmax): Accumulation Ratio of Cmax for E7777 | Cycle 5 Day 1 | 0.979 ratio |
Secondary
t1/2: Terminal Elimination Phase Half-life for E7777
11 participants were included in the PK analysis, however t1/2, could not be estimated for 1 participant due to insufficient data for elimination rate constant.
Time frame: Cycle 1 Day 1: 0-240 minutes post-infusion; Cycle 3 and 5 Day 1: 0-120 minutes post-infusion (each Cycle length = 3 weeks)
Population: The PK analysis set was defined as a group of participants who received at least 1 dose of the study drug with at least 1 serum concentration data, and included participants who had been taken frequent blood sampling for non-compartment analysis. PK-evaluable population where data at specified time points was available.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PTCL: E7777 9 mcg/kg/Day | t1/2: Terminal Elimination Phase Half-life for E7777 | Cycle 1 Day 1 | 96.0 minutes | Standard Deviation 19.6 |
| PTCL: E7777 9 mcg/kg/Day | t1/2: Terminal Elimination Phase Half-life for E7777 | Cycle 3 Day 1 | 116 minutes | — |
| PTCL: E7777 9 mcg/kg/Day | t1/2: Terminal Elimination Phase Half-life for E7777 | Cycle 5 Day 1 | 69.2 minutes | — |
Secondary
Time to Response (TTR)
TTR was defined as time between the date of administration of the first dose of the study drug and the date of first documentation PR or CR based on independent review of Efficacy and Safety Evaluation Committee. PR or CR were assessed according to modified response criteria based on the revised response criteria for malignant lymphoma (Cheson, 2007), skin lesion and peripheral blood disease were assessed according to clinical end points and response criteria in mycosis fungoides and Sezary syndrome (Olsen, 2011). TTR was only conducted among responders who had experienced CR or PR. CR: Disappearance of all evidence of disease; PR: Regression of measurable disease and no new sites.
Time frame: From the date of administration of the first dose of the study drug until date of the first documentation of PR or CR or death due to any cause (whichever occurred first) up to approximately 3 years 1 month
Population: The FAS was defined as a group of participants who received at least 1 dose of the study drug. Here overall number of participants analyzed signifies responded participants.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| PTCL: E7777 9 mcg/kg/Day | Time to Response (TTR) | 1.28 months |
| CTCL: E7777 9 mcg/kg/Day | Time to Response (TTR) | 2.12 months |
Secondary
Tmax: Time to Reach the Cmax for E7777
Time frame: Cycle 1 Day 1: 0-240 minutes post-infusion; Cycle 3 and 5 Day 1: 0-120 minutes post-infusion (each Cycle length = 3 weeks)
Population: The PK analysis set was defined as a group of participants who received at least 1 dose of the study drug with at least 1 serum concentration data, and included participants who had been taken frequent blood sampling for non-compartment analysis. PK-evaluable population where data at specified time points was available.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| PTCL: E7777 9 mcg/kg/Day | Tmax: Time to Reach the Cmax for E7777 | Cycle 1 Day 1 | 63.00 minutes |
| PTCL: E7777 9 mcg/kg/Day | Tmax: Time to Reach the Cmax for E7777 | Cycle 3 Day 1 | 65.00 minutes |
| PTCL: E7777 9 mcg/kg/Day | Tmax: Time to Reach the Cmax for E7777 | Cycle 5 Day 1 | 80.00 minutes |
Secondary
Vss: Volume of Distribution at Steady State for E7777
11 participants were included in the PK analysis, however Vss, could not be estimated for 1 participant due to insufficient data for elimination rate constant.
Time frame: Cycle 1 Day 1: 0-240 minutes post-infusion; Cycle 3 and 5 Day 1: 0-120 minutes post-infusion (each Cycle length = 3 weeks)
Population: The PK analysis set was defined as a group of participants who received at least 1 dose of the study drug with at least 1 serum concentration data, and included participants who had been taken frequent blood sampling for non-compartment analysis. PK-evaluable population where data at specified time points was available.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PTCL: E7777 9 mcg/kg/Day | Vss: Volume of Distribution at Steady State for E7777 | Cycle 1 Day 1 | 57.4 mL/kg | Standard Deviation 13.5 |
| PTCL: E7777 9 mcg/kg/Day | Vss: Volume of Distribution at Steady State for E7777 | Cycle 5 Day 1 | 44.1 mL/kg | — |
Secondary
Vz: Volume of Distribution at Terminal Phase for E7777
11 participants were included in the PK analysis, however Vz, could not be estimated for 1 participant due to insufficient data for elimination rate constant.
Time frame: Cycle 1 Day 1: 0-240 minutes post-infusion; Cycle 3 and 5 Day 1: 0-120 minutes post-infusion (each Cycle length = 3 weeks)
Population: The PK analysis set was defined as a group of participants who received at least 1 dose of the study drug with at least 1 serum concentration data, and included participants who had been taken frequent blood sampling for non-compartment analysis. PK-evaluable population where data at specified time points was available.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PTCL: E7777 9 mcg/kg/Day | Vz: Volume of Distribution at Terminal Phase for E7777 | Cycle 1 Day 1 | 59.0 milliliter per kilogram (mL/kg) | Standard Deviation 17.4 |
| PTCL: E7777 9 mcg/kg/Day | Vz: Volume of Distribution at Terminal Phase for E7777 | Cycle 5 Day 1 | 42.0 milliliter per kilogram (mL/kg) | — |