Persistent or Recurrent Cutaneous T-Cell Lymphoma
Conditions
Keywords
Persistent or Recurrent Cutaneous T-Cell Lymphoma, E7777
Brief summary
The purpose of this trial is to assess the efficacy of E7777 in participants with recurrent or persistent Cutaneous T-Cell Lymphoma (CTCL) in Stage I - III participants as assessed by objective response rate (ORR). A lead-in dose-finding part was used to determine dose level 9 microgram per kilogram (mcg/kg) E7777 that is being used to test efficacy and safety.
Detailed description
This is a multicenter, open-label study of E7777 in participants with recurrent or persistent CTCL. The study consists of an initial Lead-in part (to select recommended dose of E7777 for Main part), followed by the Main part (to test efficacy). Participants will move through three phases while on study: Pretreatment Phase, Treatment Phase, and Extension Phase and a Follow-up Period.
Interventions
DRUGE7777 9 mcg/kg
administered by intravenous (i.v.) infusion over 60 minutes (+/-10 minutes) on 5 consecutive days during every cycle of 21 days
Sponsors
Dr. Reddy's Laboratories Limited
Citius Pharmaceuticals, Inc.
Eisai Inc.
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
Participants must meet all of the following criteria to be included in the study: 1. Age greater than or equal to 18 years. 2. Histopathologic diagnosis of CTCL (mycosis fungoides \[MF\] or Sezary Syndrome \[SS\]), confirmed by skin biopsy, or lymph node, or blood assessment, of current disease. 3. CD25 assay-positive tumor, defined as detectable CD25 on greater than or equal to 20% of total lymphoid infiltrate in biopsied lesions by immunohistochemistry. 4. CTCL disease stage at study entry as follows, according to ISCL/EORTC (Olsen 2011). * Lead-In Part: Stage IA - IV, except participants with CNS involvement. * Main Study: Stage I - III 5. History of prior therapies for CTCL: must have had prior therapy, any number of prior therapies allowed. Topical treatments (except topical chemotherapy) and steroids are not considered as prior therapies. 6. A minimum washout period of 4 weeks after previous CTCL therapy is recommended before the first dose of E7777. Participants must have recovered from any adverse effects from any previous CTCL therapy to Common Terminology Criteria for Adverse Events (CTCAE) Grade \<2 before starting study drug. A shorter washout may be allowed if participant is experiencing progressive disease despite ongoing treatment. 7. Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2 in the Lead-In Part and performance status of 0 or 1 in the Main Study. 8. Life expectancy greater than or equal to 3 months in the Lead-In Part and greater than or equal to 12 months in the Main Study. 9. Adequate bone marrow reserves as evidenced by: * platelets greater than or equal to 100,000/mm\^3 (100 x 10\^9/L) * clinically stable hemoglobin greater than or equal to 9 gram per deciliter (g/dL) (90 g/L) and hematocrit greater than or equal to 27% without transfusion support 10. Normal hepatic function as evidenced by: * bilirubin \<= 1.5\* upper limit if normal (ULN) and alkaline phosphatase \<=3.0\*ULN * aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \<= 3.0\*ULN * albumin \>= 3.0 g/dL (30 g/L) 11. Adequate renal function as evidenced by serum creatinine less than or equal to 1.8 mg/dL (158 umol/L) or calculated creatinine clearance greater than or equal to 50 mL/min (per the Cockcroft-Gault formula) with less than 2+ protein or 24- hour urine creatinine clearance greater than or equal to 50 mL/minute with 24- hour urine protein less than 1gram. 12. Provide written informed consent prior to any study-specific screening procedures. 13. Females may not be lactating or pregnant at Screening or Baseline 14. All females will be considered to be of childbearing potential unless they are postmenopausal or have been sterilized surgically 15. Male participants must have had a successful vasectomy (confirmed azoospermia) or they and their female partner must meet the criteria above
Exclusion criteria
Participants who meet any of the following criteria will be excluded from the study: 1. Prior denileukin diftitox therapy 2. Use of topical steroids within 14 days of Day 1 of initial therapy is not allowed.Topical steroids or systemic low dose steroids of less than or equal to 10 milligram per day (mg/day) prednisone are allowed in participants with erythroderma who have been on corticosteroids for a prolonged period of time and where discontinuation may lead to rebound flare in disease. The concomitant steroid medication is allowed as long as the type of steroid, route of administration, and steroid dose remain the same as what the participant had been receiving for a prolonged period of time. 3. Active malignancy (except for CTCL, definitively treated basal or squamous cell carcinoma of the skin, and carcinoma in-situ of the cervix) within the past 24 months. 4. Serious intercurrent illness 5. Significant cardiac disease requiring ongoing treatment, including congestive heart failure (CHF), severe coronary artery disease (CAD), cardiomyopathy, uncontrolled cardiac arrhythmia, unstable angina pectoris, or myocardial infarction (MI) 6. Significant pulmonary symptoms or disease 7. History of uncontrolled seizure disorder or active central nervous system disease 8. Major surgery within 2 weeks of study enrollment 9. Significant or uncontrolled infections requiring systemic anti-infective therapy 10. Known human immunodeficiency virus (HIV) infection; known active hepatitis B or hepatitis C infection 11. Females who are pregnant (positive urine test) or breastfeeding 12. Any history of a medical condition or a concomitant medical condition that, in the opinion of the investigator, would compromise the participant's ability to safely complete the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Lead-In Part: Number of Participants With Dose-limiting Toxicities (DLTs) as Per National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.03 (NCI CTCAE v4.03) | Cycle 1 (cycle length was 21 days) | DLTs as per NCI CTCAE v4.03 were defined as 1) serious infusion reaction (CTCAE) Grade 4 adverse event of Infusion related reaction, or recurrent CTCAE Grade 3 despite administration of systemic steroid premedication after initial occurrence. Infusion reactions were defined as symptoms (example, fatigue, nausea, vomiting, arthralgia, myalgia, pyrexia, chills, rigors) occurring within 24 hours of E7777 infusion. 2) Capillary leak syndrome (CLS) CTCAE Grade 4 or Grade 3 (with exceptions). A CLS event was defined as the noted occurrence of at least 2 of the following: hypotension, edema, or serum albumin less than (\<) 3.0 gram per decilitre (g/dL). 3) Clinical visual impairment. 4) Any CTCAE Grade greater than or equal to (\>=) 4 adverse event (AE) that may represent an infusion reaction. 5) Any other Grade 3 or greater toxicity assessed as related to E7777 treatment and which in the opinion of a safety consultancy investigator panel, was a dose-limiting toxicity. |
| Lead-In Part: Maximum Tolerated Dose (MTD) of E7777 | Cycle 1 (cycle length was 21 days) | The MTD was defined as the safe dose level established in Lead-In Part. MTD was determined by summarizing the number and percentage of participants with DLTs for the first cycle, by study dosing schedule, initial dosing level and overall for the Lead-In Part. |
| Main Study Part: Objective Response Rate (ORR) by Independent Review Committee (IRC) Based on Olsen 2011 Criteria | From the date of administration of the first dose of the study drug until disease progression (Up to 3 years 6 months) | 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 committee on 2 assessments at least 3 weeks apart. The tumor response was based on global response score (GRS) Olsen 2011 criteria. CR was defined as disappearance of all evidence of disease and PR was defined as regression of measurable disease and no new sites. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Main Study Part: Time to Response (TTR) Per Independent Review Committee | From the date of administration of the first dose of the study drug until date of the first documentation of PR or CR (Up to 3 years 6 months) | Time to response per independent review committee was defined as the time from date of first dose to the date of the first documented CR or PR. The tumor assessment was based on GRS Olsen 2011 criteria. CR was defined as disappearance of all evidence of disease and PR was defined as regression of measurable disease and no new sites. |
| Lead-In Part and Main Study Part: ORR Per Investigator Assessment | From the date of administration of the first dose of the study drug until disease progression (Up to 3 years 6 months) | ORR per investigator assessment was defined as the percentage of participants whose BOR was CR or PR. The tumor response was based on GRS Olsen 2011 criteria. CR was defined as disappearance of all evidence of disease and PR was defined as regression of measurable disease and no new sites. |
| Main Study Part: ORR Per IRC Based on Prince 2010 Criteria | From the date of administration of the first dose of the study drug until disease progression (Up to 3 years 6 months) | ORR was defined as the percentage of participants whose BOR was CR, clinical complete response (CCR) or PR per IRC. The tumor response was based on Prince 2010 criteria. CR was defined as disappearance of all evidence of disease and PR was defined as regression of measurable disease and no new sites. CCR was defined as tumor residue not visible on esophagogram, computed tomography (CT), endoscopy, positron emission tomography (PET)-CT. |
| Lead-In Part and Main Study Part: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | From the first dose of study drug up to 30 days after the last dose (Up to 3 years and 7 months) | TEAE was defined as an adverse event that had an onset date, or a worsening in severity on or after the first dose of study drug up to the end of the study. SAE was any untoward medical occurrence that at any dose: resulted in death; life threatening required inpatient hospitalization; resulted in persistent, significant disability; was congenital anomaly/birth defect or medically important due to other reasons than mentioned criteria. Number of participants with TEAEs and SAEs were reported. |
| Lead-In Part: Maximum Serum Concentration (Cmax) of E7777 | Cycles 1, 3, 5 Day 1: Pre-dose up to 300 minutes post-dose (Cycle length was 21 days) | Participants were not available for analysis in 15 mcg/kg (Cycles 3 and 5), 6 mcg/kg (Cycle 5), 9 mcg/kg (Cycles 3 and 5), 12 mcg/kg (Cycle 3), hence no Pharmacokinetic (PK) data was collected and analyzed for these doses and cycles. |
| Main Study Part: Maximum Serum Concentration (Cmax) of E7777 | Cycles 1, 3 and 5 Day 1: Pre-dose up to 300 minutes post-dose (Cycle length was 21 days) | — |
| Lead-In Part: Area Under the Curve From Time 0 to Time t (AUC[0-t]) of E7777 | Cycles 1, 3, 5 Day 1: Pre-dose up to 300 hours Post-dose (Cycle length was 21 days) | Participants were not available for analysis in 15 mcg/kg (Cycles 3 and 5), 6 mcg/kg (Cycle 5), 9 mcg/kg (Cycles 3 and 5), 12 mcg/kg (Cycle 3), hence no PK data was collected and analyzed for these doses and cycles. Here, min\*ng/mL means minute\*nanogram per milliliter. |
| Main Study Part: Area Under the Curve From Time 0 to Time t (AUC[0-t]) of E7777 | Cycles 1, 3 and 5 Day 1: Pre-dose up to 300 hours post-dose (Cycle length was 21 days) | — |
| Lead-In Part: Area Under the Curve From Time 0 to Time Infinity (AUC[0-inf]) of E7777 | Cycles 1, 3, 5 Day 1: Pre-dose up to 300 hours post-dose (Cycle length was 21 days) | Participants were not available for analysis in 15 mcg/kg (Cycles 3 and 5), 6 mcg/kg (Cycle 5), 9 mcg/kg (Cycles 3 and 5), 12 mcg/kg (Cycle 3), hence no PK data was collected and analyzed for these doses and cycles. |
| Main Study Part: Area Under the Curve From Time 0 to Time Infinity (AUC[0-inf]) of E7777 | Cycles 1, 3 and 5 Day 1: Pre-dose up to 300 hours post-dose (Cycle length was 21 days) | Participants were not available for analysis at Cycle 3 Day 1, hence no PK data was collected and analyzed for this timepoint. |
| Lead-In Part: Terminal Elimination Half-life (t1/2) of E7777 | Cycles 1, 3, 5 Day 1: Pre-dose up to 300 hours post-dose (Cycle length was 21 days) | Participants were not available for analysis in 15 mcg/kg (Cycles 3 and 5), 6 mcg/kg (Cycle 5), 9 mcg/kg (Cycles 3 and 5), 12 mcg/kg (Cycle 3), hence no PK data was collected and analyzed for these doses and cycles. |
| Lead-In Part: Duration of Response (DOR) Per Investigator Assessment | From the date of first documentation of CR or PR until date of the first documentation of PD or death due to any cause (Up to 1 year 2 months) | DOR per investigator assessment was defined as the time from date when criteria for response (CR or PR) was first met until the date of the first documentation of disease progression (PD) or date of death from any cause. The tumor assessment was based on GRS Olsen 2011 criteria. CR was defined as disappearance of all evidence of disease and PR was defined as regression of measurable disease and no new sites. PD was defined as any new lesion or unequivocally increase of previously involved sites from nadir. |
| Lead-In Part: Time to Reach Maximum (Peak) Concentration After Drug Administration (Tmax) | Cycles 1, 3, 5 Day 1: Pre-dose up to 300 hours post-dose (Cycle length was 21 days) | Participants were not available for analysis in 15 mcg/kg (Cycles 3 and 5), 6 mcg/kg (Cycle 5), 9 mcg/kg (Cycles 3 and 5), 12 mcg/kg (Cycle 3), hence no PK data was collected and analyzed for these doses and cycles. |
| Main Study Part: Time to Reach Maximum (Peak) Concentration After Drug Administration (Tmax) | Cycles 1, 3 and 5 Day 1: Pre-dose up to 300 hours post-dose (Cycle length was 21 days) | — |
| Lead-In Part: Total Body Clearance (CL) of E7777 | Cycles 1, 3, 5 Day 1: Pre-dose up to 300 hours post-dose (Cycle length was 21 days) | Participants were not available for analysis in 15 mcg/kg (Cycles 3 and 5), 6 mcg/kg (Cycle 5), 9 mcg/kg (Cycles 3 and 5), 12 mcg/kg (Cycle 3), hence no PK data was collected and analyzed for these doses and cycles. Here, mL/min/kg means milliliter per minute per kilogram. |
| Main Study Part: Total Body Clearance (CL) of E7777 | Cycles 1, 3 and 5 Day 1: Pre-dose up to 300 hours post-dose (Cycle length was 21 days) | Participants were not available for analysis at Cycle 3 Day 1, hence no PK data was collected and analyzed for this timepoint. |
| Lead-In Part: Volume of Distribution at Steady State (Vdss) of E7777 | Cycles 1, 3, 5 Day 1: Pre-dose up to 300 hours post-dose (Cycle length was 21 days) | Participants were not available for analysis in 15 mcg/kg (Cycles 3 and 5), 6 mcg/kg (Cycle 5), 9 mcg/kg (Cycles 3 and 5), 12 mcg/kg (Cycle 3), hence no PK data was collected and analyzed for these doses and cycles. |
| Main Study Part: Volume of Distribution at Steady State (Vdss) of E7777 | Cycles 1, 3 and 5 Day 1: Pre-dose up to 300 hours post-dose (Cycle length was 21 days) | Participants were not available for analysis at Cycle 3 Day 1, hence no PK data was collected and analyzed for this timepoint. |
| Lead-In Part: Percentage of Participants Testing Positive for Anti-E7777 and Anti-interleukin (IL)-2 Antibodies | Cycle 1 Day 1, Cycle 2 Day 1, Cycle 3 Day 1, Cycle 5 Day 1 | Immunogenicity was assessed by determining the anti-E7777 and anti-IL-2 antibodies in serum using validated methods. Percentage of participants testing positive for Anti-E7777 and Anti-IL-2 antibodies were reported. |
| Main Study Part: Percentage of Participants Testing Positive for Anti-E7777 and Anti-IL-2 Antibodies | Cycle 1 Day 1, Cycle 2 Day 1, Cycle 3 Day 1 | Immunogenicity was assessed by determining the anti-E7777 and anti-IL-2 antibodies in serum using validated methods. Percentage of participants testing positive for Anti-E7777 and Anti-IL-2 antibodies were reported. |
| Main Study Part: Number of Participants With Objective Skin Response | Up to 30 months | Modified severity weighted assessment tool (mSWAT) was used to measure skin disease severity based on the percentage of body surface area (BSA) with patches, plaques, or tumors. Total scores were calculated by multiplying the BSA percentage for each category of lesion (patch, plaque, or tumor) by a weighting factor and adding the three sub-scores which ranged from 0 (unaffected) to 400 (severely affected). Lower scores indicated a lower degree of skin disease severity. CR corresponded to 100% clearance of skin lesions present at baseline (mSWAT score of 0). PR corresponded to 50-99% clearance of skin disease present at baseline (at least 50% reduction in mSWAT score), without new tumors. |
| Main Study Part: Duration of Skin Response | Up to 30 months | The duration of skin response based on the mSWAT score was defined as time from the date when criteria for skin response (CR or PR) was first met until the date of documented PD or death due to any cause for those participants with a confirmed PR or CR. mSWAT was used to measure skin disease severity based on the percentage of BSA with patches, plaques, or tumors. Total scores were calculated by multiplying the BSA percentage for each category of lesion (patch, plaque, or tumor) by a weighting factor and adding the three sub-scores which ranged from 0 (unaffected) to 400 (severely affected). Lower scores indicated a lower degree of skin disease severity. CR corresponded to 100% clearance of skin lesions present at baseline (mSWAT score of 0). PR corresponded to 50-99% clearance of skin disease present at baseline (at least 50% reduction in mSWAT score), without new tumors. |
| Main Study Part: Time to Skin Response | Up to 30 months | The time to skin response based on the mSWAT score was defined as time from the date of first dose to the date when criteria for skin response (CR or PR) were first met. mSWAT was used to measure skin disease severity based on the percentage of BSA with patches, plaques, or tumors. Total scores were calculated by multiplying the BSA percentage for each category of lesion (patch, plaque, or tumor) by a weighting factor and adding the three sub-scores which ranged from 0 (unaffected) to 400 (severely affected). Lower scores indicated a lower degree of skin disease severity. CR corresponded to 100% clearance of skin lesions present at baseline (mSWAT score of 0). PR corresponded to 50-99% clearance of skin disease present at baseline (at least 50% reduction in mSWAT score), without new tumors. |
| Main Study Part: Terminal Elimination Half-life (t1/2) of E7777 | Cycles 1, 3 and 5 Day 1: Pre-dose up to 300 hours post-dose (Cycle length was 21 days) | — |
| Main Study Part: Duration of Response (DOR) Per Independent Review Committee | From the date of first documentation of CR or PR until date of the first documentation of PD or death due to any cause (Up to 3 years 6 months) | DOR per independent review committee was defined as the time from the date when criteria for response (CR or PR) was first met until the date of the first documentation of PD or date of death from any cause. The tumor assessment was based on GRS Olsen 2011 criteria. CR was defined as disappearance of all evidence of disease and PR was defined as regression of measurable disease and no new sites. PD was defined as any new lesion or unequivocally increase of previously involved sites from nadir. |
| Lead-In Part: Time to Response (TTR) Per Investigator Assessment | From the date of administration of the first dose of the study drug until date of the first documentation of PR or CR (Up to 1 year 2 months) | Time to response per investigator assessment was defined as the time from date of first dose to the date of the first documented CR or PR. The tumor assessment was based on GRS Olsen 2011 criteria. CR was defined as disappearance of all evidence of disease and PR was defined as regression of measurable disease and no new sites. |
Countries
Australia, Puerto Rico, United States
Participant flow
Recruitment details
Participants took part in the study at 20 investigative sites in the United States and Australia from 30 May 2013 to 14 December 2021.
Pre-assignment details
36 participants were screened in Lead-In Part, out of which 21 were enrolled and treated.143 participants were screened in Main Study Part, out of which 91 were enrolled and 90 were treated. As per planned analysis, data was collectively reported for total 98 participants (Full analysis set/Safety analysis set) from Main Study Part and Lead-In Part who received study drug at 9 micrograms per kilograms (mcg/kg) dose. 8 participants were from Lead-In Part and 90 were from Main Study Part.
Participants by arm
| Arm | Count |
|---|---|
| Lead-In Part: E7777 6 mcg/kg Participants were treated with E7777 6 mcg/kg by IV infusion over 60 minutes on 5 consecutive days in 21-day cycles for up to 8 cycles or disease progression or unacceptable toxicity in Lead-in part. | 2 |
| Lead-In Part: E7777 12 mcg/kg Participants were treated with E7777 12 mcg/kg by IV infusion over 60 minutes on 5 consecutive days in 21-day cycles for up to 8 cycles or disease progression or unacceptable toxicity in Lead-in part. | 9 |
| Lead-In Part: E7777 15 mcg/kg Participants were treated with E7777 15 mcg/kg by IV infusion over 60 minutes on 5 consecutive days in 21-day cycles for up to 8 cycles or disease progression or unacceptable toxicity in Lead-in part. | 2 |
| Lead-In Part and Main Study Part: E7777 9 mcg/kg Participants were treated with E7777 9 mcg/kg by IV infusion over 60 minutes on 5 consecutive days in 21-day cycles for up to 8 cycles or disease progression or unacceptable toxicity in Lead-in part and in Main study part and were presented together here, as planned. | 98 |
| Total | 111 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Lead-In Part (1 Year 2 Months) | Disease Progression | 1 | 4 | 4 | 0 | 0 |
| Main Study Part (2 Years 4 Months) | Disease progression | 0 | 0 | 0 | 0 | 20 |
| Main Study Part (2 Years 4 Months) | Lost to Follow-up | 0 | 0 | 0 | 0 | 2 |
| Main Study Part (2 Years 4 Months) | Not treated | 0 | 0 | 0 | 0 | 1 |
| Main Study Part (2 Years 4 Months) | Other | 0 | 0 | 0 | 0 | 2 |
| Main Study Part (2 Years 4 Months) | Sponsor Decision | 0 | 0 | 0 | 0 | 11 |
| Main Study Part (2 Years 4 Months) | Withdrawal by Subject | 0 | 0 | 0 | 0 | 9 |
Baseline characteristics
| Characteristic | Lead-In Part: E7777 6 mcg/kg | Lead-In Part: E7777 12 mcg/kg | Lead-In Part: E7777 15 mcg/kg | Lead-In Part and Main Study Part: E7777 9 mcg/kg | Total |
|---|---|---|---|---|---|
| Age, Continuous | 54.0 years STANDARD_DEVIATION 22.63 | 58.4 years STANDARD_DEVIATION 15.88 | 69.0 years STANDARD_DEVIATION 2.83 | 62.9 years STANDARD_DEVIATION 11.91 | 62.5 years STANDARD_DEVIATION 12.32 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 1 Participants | 0 Participants | 14 Participants | 15 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 2 Participants | 8 Participants | 2 Participants | 81 Participants | 93 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 3 Participants | 3 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 2 Participants | 1 Participants | 16 Participants | 20 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 8 Participants | 8 Participants |
| Race (NIH/OMB) White | 1 Participants | 7 Participants | 1 Participants | 73 Participants | 82 Participants |
| Sex: Female, Male Female | 2 Participants | 4 Participants | 2 Participants | 37 Participants | 45 Participants |
| Sex: Female, Male Male | 0 Participants | 5 Participants | 0 Participants | 61 Participants | 66 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 2 | 3 / 9 | 0 / 2 | 13 / 98 |
| other Total, other adverse events | 2 / 2 | 9 / 9 | 1 / 2 | 95 / 98 |
| serious Total, serious adverse events | 0 / 2 | 4 / 9 | 2 / 2 | 36 / 98 |
Outcome results
Primary
Lead-In Part: Maximum Tolerated Dose (MTD) of E7777
The MTD was defined as the safe dose level established in Lead-In Part. MTD was determined by summarizing the number and percentage of participants with DLTs for the first cycle, by study dosing schedule, initial dosing level and overall for the Lead-In Part.
Time frame: Cycle 1 (cycle length was 21 days)
Population: Dose-finding analysis set included all participants in the Lead-in part who completed Cycle 1 treatment and were evaluated for DLT, and those who discontinued during Cycle 1 due to DLT.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Lead-In Part: E7777 6 mcg/kg | Lead-In Part: Maximum Tolerated Dose (MTD) of E7777 | 12.0 mcg/kg |
Primary
Lead-In Part: Number of Participants With Dose-limiting Toxicities (DLTs) as Per National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.03 (NCI CTCAE v4.03)
DLTs as per NCI CTCAE v4.03 were defined as 1) serious infusion reaction (CTCAE) Grade 4 adverse event of Infusion related reaction, or recurrent CTCAE Grade 3 despite administration of systemic steroid premedication after initial occurrence. Infusion reactions were defined as symptoms (example, fatigue, nausea, vomiting, arthralgia, myalgia, pyrexia, chills, rigors) occurring within 24 hours of E7777 infusion. 2) Capillary leak syndrome (CLS) CTCAE Grade 4 or Grade 3 (with exceptions). A CLS event was defined as the noted occurrence of at least 2 of the following: hypotension, edema, or serum albumin less than (\<) 3.0 gram per decilitre (g/dL). 3) Clinical visual impairment. 4) Any CTCAE Grade greater than or equal to (\>=) 4 adverse event (AE) that may represent an infusion reaction. 5) Any other Grade 3 or greater toxicity assessed as related to E7777 treatment and which in the opinion of a safety consultancy investigator panel, was a dose-limiting toxicity.
Time frame: Cycle 1 (cycle length was 21 days)
Population: Lead-in analysis set included all participants enrolled in lead-in part.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Lead-In Part: E7777 6 mcg/kg | Lead-In Part: Number of Participants With Dose-limiting Toxicities (DLTs) as Per National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.03 (NCI CTCAE v4.03) | 0 Participants |
| Lead-In Part: E7777 9 mcg/kg | Lead-In Part: Number of Participants With Dose-limiting Toxicities (DLTs) as Per National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.03 (NCI CTCAE v4.03) | 0 Participants |
| Lead-In Part: E7777 12 mcg/kg | Lead-In Part: Number of Participants With Dose-limiting Toxicities (DLTs) as Per National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.03 (NCI CTCAE v4.03) | 0 Participants |
| Lead-In Part: E7777 15 mcg/kg | Lead-In Part: Number of Participants With Dose-limiting Toxicities (DLTs) as Per National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.03 (NCI CTCAE v4.03) | 2 Participants |
Primary
Main Study Part: Objective Response Rate (ORR) by Independent Review Committee (IRC) Based on Olsen 2011 Criteria
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 committee on 2 assessments at least 3 weeks apart. The tumor response was based on global response score (GRS) Olsen 2011 criteria. CR was defined as disappearance of all evidence of disease and PR was defined as regression of measurable disease and no new sites.
Time frame: From the date of administration of the first dose of the study drug until disease progression (Up to 3 years 6 months)
Population: Primary efficacy analysis set included all participants with Stages I to III CTCL (both Main Study and Lead-In part) who received study drug at the 9 mcg/kg dose
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Lead-In Part: E7777 6 mcg/kg | Main Study Part: Objective Response Rate (ORR) by Independent Review Committee (IRC) Based on Olsen 2011 Criteria | 36.2 percentage of participants |
Secondary
Lead-In Part and Main Study Part: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
TEAE was defined as an adverse event that had an onset date, or a worsening in severity on or after the first dose of study drug up to the end of the study. SAE was any untoward medical occurrence that at any dose: resulted in death; life threatening required inpatient hospitalization; resulted in persistent, significant disability; was congenital anomaly/birth defect or medically important due to other reasons than mentioned criteria. Number of participants with TEAEs and SAEs were reported.
Time frame: From the first dose of study drug up to 30 days after the last dose (Up to 3 years and 7 months)
Population: Lead-In Part: SAS included all participants who received study drug. Main Study Part: SAS included all participants (both Main Study and Lead-In) who received study drug at 9 mcg/kg.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Lead-In Part: E7777 6 mcg/kg | Lead-In Part and Main Study Part: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | TEAEs | 2 Participants |
| Lead-In Part: E7777 6 mcg/kg | Lead-In Part and Main Study Part: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | SAEs | 0 Participants |
| Lead-In Part: E7777 9 mcg/kg | Lead-In Part and Main Study Part: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | SAEs | 4 Participants |
| Lead-In Part: E7777 9 mcg/kg | Lead-In Part and Main Study Part: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | TEAEs | 9 Participants |
| Lead-In Part: E7777 12 mcg/kg | Lead-In Part and Main Study Part: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | TEAEs | 2 Participants |
| Lead-In Part: E7777 12 mcg/kg | Lead-In Part and Main Study Part: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | SAEs | 2 Participants |
| Lead-In Part: E7777 15 mcg/kg | Lead-In Part and Main Study Part: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | TEAEs | 97 Participants |
| Lead-In Part: E7777 15 mcg/kg | Lead-In Part and Main Study Part: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | SAEs | 36 Participants |
Secondary
Lead-In Part and Main Study Part: ORR Per Investigator Assessment
ORR per investigator assessment was defined as the percentage of participants whose BOR was CR or PR. The tumor response was based on GRS Olsen 2011 criteria. CR was defined as disappearance of all evidence of disease and PR was defined as regression of measurable disease and no new sites.
Time frame: From the date of administration of the first dose of the study drug until disease progression (Up to 3 years 6 months)
Population: Lead-in analysis set included all participants enrolled in the lead-in part and Investigator efficacy analysis set included all Stage I to III participants (both Main Study \[n=66\] and Lead-In \[n=5\]) who received study drug at 9 mcg/kg dose.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Lead-In Part: E7777 6 mcg/kg | Lead-In Part and Main Study Part: ORR Per Investigator Assessment | 50.0 percentage of participants |
| Lead-In Part: E7777 9 mcg/kg | Lead-In Part and Main Study Part: ORR Per Investigator Assessment | 50.0 percentage of participants |
| Lead-In Part: E7777 12 mcg/kg | Lead-In Part and Main Study Part: ORR Per Investigator Assessment | 33.3 percentage of participants |
| Lead-In Part: E7777 15 mcg/kg | Lead-In Part and Main Study Part: ORR Per Investigator Assessment | 0 percentage of participants |
| Main Study Part: E7777 9 mcg/kg | Lead-In Part and Main Study Part: ORR Per Investigator Assessment | 42.3 percentage of participants |
Secondary
Lead-In Part: Area Under the Curve From Time 0 to Time Infinity (AUC[0-inf]) of E7777
Participants were not available for analysis in 15 mcg/kg (Cycles 3 and 5), 6 mcg/kg (Cycle 5), 9 mcg/kg (Cycles 3 and 5), 12 mcg/kg (Cycle 3), hence no PK data was collected and analyzed for these doses and cycles.
Time frame: Cycles 1, 3, 5 Day 1: Pre-dose up to 300 hours post-dose (Cycle length was 21 days)
Population: Lead-in PK analysis set included all participants who received at least one dose of study drug and from whom at least one valid E7777 PK parameter was obtained. Here overall number of participants analyzed signifies participants who were evaluable for this outcome measure. Here number analyzed signifies participants who were evaluable for this outcome measure for given timepoints.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Lead-In Part: E7777 6 mcg/kg | Lead-In Part: Area Under the Curve From Time 0 to Time Infinity (AUC[0-inf]) of E7777 | Cycle 1 Day 1 | 20600 min*ng/mL | Standard Deviation 7850 |
| Lead-In Part: E7777 6 mcg/kg | Lead-In Part: Area Under the Curve From Time 0 to Time Infinity (AUC[0-inf]) of E7777 | Cycle 3 Day 1 | 4960 min*ng/mL | — |
| Lead-In Part: E7777 9 mcg/kg | Lead-In Part: Area Under the Curve From Time 0 to Time Infinity (AUC[0-inf]) of E7777 | Cycle 1 Day 1 | 27000 min*ng/mL | Standard Deviation 16500 |
| Lead-In Part: E7777 12 mcg/kg | Lead-In Part: Area Under the Curve From Time 0 to Time Infinity (AUC[0-inf]) of E7777 | Cycle 1 Day 1 | 30000 min*ng/mL | Standard Deviation 12900 |
| Lead-In Part: E7777 12 mcg/kg | Lead-In Part: Area Under the Curve From Time 0 to Time Infinity (AUC[0-inf]) of E7777 | Cycle 5 Day 1 | 6900 min*ng/mL | — |
| Lead-In Part: E7777 15 mcg/kg | Lead-In Part: Area Under the Curve From Time 0 to Time Infinity (AUC[0-inf]) of E7777 | Cycle 1 Day 1 | 43500 min*ng/mL | — |
Secondary
Lead-In Part: Area Under the Curve From Time 0 to Time t (AUC[0-t]) of E7777
Participants were not available for analysis in 15 mcg/kg (Cycles 3 and 5), 6 mcg/kg (Cycle 5), 9 mcg/kg (Cycles 3 and 5), 12 mcg/kg (Cycle 3), hence no PK data was collected and analyzed for these doses and cycles. Here, min\*ng/mL means minute\*nanogram per milliliter.
Time frame: Cycles 1, 3, 5 Day 1: Pre-dose up to 300 hours Post-dose (Cycle length was 21 days)
Population: Lead-in PK analysis set included all participants who received at least one dose of study drug and from whom at least one valid E7777 PK parameter was obtained. Here overall number of participants analyzed signifies participants who were evaluable for this outcome measure. Here number analyzed signifies participants who were evaluable for this outcome measure for given timepoints.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Lead-In Part: E7777 6 mcg/kg | Lead-In Part: Area Under the Curve From Time 0 to Time t (AUC[0-t]) of E7777 | Cycle 1 Day 1 | 18500 min*ng/mL | Standard Deviation 6080 |
| Lead-In Part: E7777 6 mcg/kg | Lead-In Part: Area Under the Curve From Time 0 to Time t (AUC[0-t]) of E7777 | Cycle 3 Day 1 | 4670 min*ng/mL | — |
| Lead-In Part: E7777 9 mcg/kg | Lead-In Part: Area Under the Curve From Time 0 to Time t (AUC[0-t]) of E7777 | Cycle 1 Day 1 | 18200 min*ng/mL | Standard Deviation 13100 |
| Lead-In Part: E7777 12 mcg/kg | Lead-In Part: Area Under the Curve From Time 0 to Time t (AUC[0-t]) of E7777 | Cycle 1 Day 1 | 23600 min*ng/mL | Standard Deviation 12900 |
| Lead-In Part: E7777 12 mcg/kg | Lead-In Part: Area Under the Curve From Time 0 to Time t (AUC[0-t]) of E7777 | Cycle 5 Day 1 | 6730 min*ng/mL | — |
| Lead-In Part: E7777 15 mcg/kg | Lead-In Part: Area Under the Curve From Time 0 to Time t (AUC[0-t]) of E7777 | Cycle 1 Day 1 | 39800 min*ng/mL | Standard Deviation 4170 |
Secondary
Lead-In Part: Duration of Response (DOR) Per Investigator Assessment
DOR per investigator assessment was defined as the time from date when criteria for response (CR or PR) was first met until the date of the first documentation of disease progression (PD) or date of death from any cause. The tumor assessment was based on GRS Olsen 2011 criteria. CR was defined as disappearance of all evidence of disease and PR was defined as regression of measurable disease and no new sites. PD was defined as any new lesion or unequivocally increase of previously involved sites from nadir.
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 (Up to 1 year 2 months)
Population: Lead-in analysis set included all participants enrolled in the Lead-in part. Here, 'overall number of participants analyzed' were those who had CR or PR in lead in part.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Lead-In Part: E7777 6 mcg/kg | Lead-In Part: Duration of Response (DOR) Per Investigator Assessment | 43.0 days |
| Lead-In Part: E7777 9 mcg/kg | Lead-In Part: Duration of Response (DOR) Per Investigator Assessment | 106.0 days |
| Lead-In Part: E7777 12 mcg/kg | Lead-In Part: Duration of Response (DOR) Per Investigator Assessment | 113.0 days |
Secondary
Lead-In Part: Maximum Serum Concentration (Cmax) of E7777
Participants were not available for analysis in 15 mcg/kg (Cycles 3 and 5), 6 mcg/kg (Cycle 5), 9 mcg/kg (Cycles 3 and 5), 12 mcg/kg (Cycle 3), hence no Pharmacokinetic (PK) data was collected and analyzed for these doses and cycles.
Time frame: Cycles 1, 3, 5 Day 1: Pre-dose up to 300 minutes post-dose (Cycle length was 21 days)
Population: Lead-in PK analysis set included all participants who received at least one dose of study drug and from whom at least one valid E7777 PK parameter was obtained. Here overall number of participants analyzed signifies participants who were evaluable for this outcome measure. Here number analyzed signifies participants who were evaluable for this outcome measure for given timepoints.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Lead-In Part: E7777 6 mcg/kg | Lead-In Part: Maximum Serum Concentration (Cmax) of E7777 | Cycle 1 Day 1 | 135 nanogram per milliliter (ng/mL) | Standard Deviation 26.2 |
| Lead-In Part: E7777 6 mcg/kg | Lead-In Part: Maximum Serum Concentration (Cmax) of E7777 | Cycle 3 Day 1 | 59.5 nanogram per milliliter (ng/mL) | — |
| Lead-In Part: E7777 9 mcg/kg | Lead-In Part: Maximum Serum Concentration (Cmax) of E7777 | Cycle 1 Day 1 | 118 nanogram per milliliter (ng/mL) | Standard Deviation 70.8 |
| Lead-In Part: E7777 12 mcg/kg | Lead-In Part: Maximum Serum Concentration (Cmax) of E7777 | Cycle 1 Day 1 | 183 nanogram per milliliter (ng/mL) | Standard Deviation 65.3 |
| Lead-In Part: E7777 12 mcg/kg | Lead-In Part: Maximum Serum Concentration (Cmax) of E7777 | Cycle 5 Day 1 | 105 nanogram per milliliter (ng/mL) | — |
| Lead-In Part: E7777 15 mcg/kg | Lead-In Part: Maximum Serum Concentration (Cmax) of E7777 | Cycle 1 Day 1 | 383 nanogram per milliliter (ng/mL) | Standard Deviation 133 |
Secondary
Lead-In Part: Percentage of Participants Testing Positive for Anti-E7777 and Anti-interleukin (IL)-2 Antibodies
Immunogenicity was assessed by determining the anti-E7777 and anti-IL-2 antibodies in serum using validated methods. Percentage of participants testing positive for Anti-E7777 and Anti-IL-2 antibodies were reported.
Time frame: Cycle 1 Day 1, Cycle 2 Day 1, Cycle 3 Day 1, Cycle 5 Day 1
Population: Lead-in PK Analysis Set included all participants who received at least one dose of study drug and from whom at least one valid E7777 PK parameter was obtained.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Lead-In Part: E7777 6 mcg/kg | Lead-In Part: Percentage of Participants Testing Positive for Anti-E7777 and Anti-interleukin (IL)-2 Antibodies | Cycle 1 Day 1 (Anti-E7777 Antibodies) | 50.0 percentage of participants |
| Lead-In Part: E7777 6 mcg/kg | Lead-In Part: Percentage of Participants Testing Positive for Anti-E7777 and Anti-interleukin (IL)-2 Antibodies | Cycle 2 Day 1 (Anti-E7777 Antibodies) | 100.0 percentage of participants |
| Lead-In Part: E7777 6 mcg/kg | Lead-In Part: Percentage of Participants Testing Positive for Anti-E7777 and Anti-interleukin (IL)-2 Antibodies | Cycle 3 Day 1 (Anti-E7777 Antibodies) | 100.0 percentage of participants |
| Lead-In Part: E7777 6 mcg/kg | Lead-In Part: Percentage of Participants Testing Positive for Anti-E7777 and Anti-interleukin (IL)-2 Antibodies | Cycle 5 Day 1 (Anti-E7777 Antibodies) | 100.0 percentage of participants |
| Lead-In Part: E7777 6 mcg/kg | Lead-In Part: Percentage of Participants Testing Positive for Anti-E7777 and Anti-interleukin (IL)-2 Antibodies | Cycle 1 Day 1 (Anti-IL-2 Antibodies) | 0 percentage of participants |
| Lead-In Part: E7777 6 mcg/kg | Lead-In Part: Percentage of Participants Testing Positive for Anti-E7777 and Anti-interleukin (IL)-2 Antibodies | Cycle 2 Day 1 (Anti-IL-2 Antibodies) | 0 percentage of participants |
| Lead-In Part: E7777 6 mcg/kg | Lead-In Part: Percentage of Participants Testing Positive for Anti-E7777 and Anti-interleukin (IL)-2 Antibodies | Cycle 3 Day 1 (Anti-IL-2 Antibodies) | 100.0 percentage of participants |
| Lead-In Part: E7777 6 mcg/kg | Lead-In Part: Percentage of Participants Testing Positive for Anti-E7777 and Anti-interleukin (IL)-2 Antibodies | Cycle 5 Day 1 (Anti-IL-2 Antibodies) | 100.0 percentage of participants |
| Lead-In Part: E7777 9 mcg/kg | Lead-In Part: Percentage of Participants Testing Positive for Anti-E7777 and Anti-interleukin (IL)-2 Antibodies | Cycle 2 Day 1 (Anti-IL-2 Antibodies) | 87.5 percentage of participants |
| Lead-In Part: E7777 9 mcg/kg | Lead-In Part: Percentage of Participants Testing Positive for Anti-E7777 and Anti-interleukin (IL)-2 Antibodies | Cycle 1 Day 1 (Anti-IL-2 Antibodies) | 37.5 percentage of participants |
| Lead-In Part: E7777 9 mcg/kg | Lead-In Part: Percentage of Participants Testing Positive for Anti-E7777 and Anti-interleukin (IL)-2 Antibodies | Cycle 2 Day 1 (Anti-E7777 Antibodies) | 100.0 percentage of participants |
| Lead-In Part: E7777 9 mcg/kg | Lead-In Part: Percentage of Participants Testing Positive for Anti-E7777 and Anti-interleukin (IL)-2 Antibodies | Cycle 5 Day 1 (Anti-IL-2 Antibodies) | 83.3 percentage of participants |
| Lead-In Part: E7777 9 mcg/kg | Lead-In Part: Percentage of Participants Testing Positive for Anti-E7777 and Anti-interleukin (IL)-2 Antibodies | Cycle 3 Day 1 (Anti-IL-2 Antibodies) | 100.0 percentage of participants |
| Lead-In Part: E7777 9 mcg/kg | Lead-In Part: Percentage of Participants Testing Positive for Anti-E7777 and Anti-interleukin (IL)-2 Antibodies | Cycle 5 Day 1 (Anti-E7777 Antibodies) | 100.0 percentage of participants |
| Lead-In Part: E7777 9 mcg/kg | Lead-In Part: Percentage of Participants Testing Positive for Anti-E7777 and Anti-interleukin (IL)-2 Antibodies | Cycle 3 Day 1 (Anti-E7777 Antibodies) | 100.0 percentage of participants |
| Lead-In Part: E7777 9 mcg/kg | Lead-In Part: Percentage of Participants Testing Positive for Anti-E7777 and Anti-interleukin (IL)-2 Antibodies | Cycle 1 Day 1 (Anti-E7777 Antibodies) | 100.0 percentage of participants |
| Lead-In Part: E7777 12 mcg/kg | Lead-In Part: Percentage of Participants Testing Positive for Anti-E7777 and Anti-interleukin (IL)-2 Antibodies | Cycle 3 Day 1 (Anti-IL-2 Antibodies) | 100.0 percentage of participants |
| Lead-In Part: E7777 12 mcg/kg | Lead-In Part: Percentage of Participants Testing Positive for Anti-E7777 and Anti-interleukin (IL)-2 Antibodies | Cycle 3 Day 1 (Anti-E7777 Antibodies) | 100.0 percentage of participants |
| Lead-In Part: E7777 12 mcg/kg | Lead-In Part: Percentage of Participants Testing Positive for Anti-E7777 and Anti-interleukin (IL)-2 Antibodies | Cycle 5 Day 1 (Anti-E7777 Antibodies) | 100.0 percentage of participants |
| Lead-In Part: E7777 12 mcg/kg | Lead-In Part: Percentage of Participants Testing Positive for Anti-E7777 and Anti-interleukin (IL)-2 Antibodies | Cycle 1 Day 1 (Anti-IL-2 Antibodies) | 33.3 percentage of participants |
| Lead-In Part: E7777 12 mcg/kg | Lead-In Part: Percentage of Participants Testing Positive for Anti-E7777 and Anti-interleukin (IL)-2 Antibodies | Cycle 2 Day 1 (Anti-IL-2 Antibodies) | 83.3 percentage of participants |
| Lead-In Part: E7777 12 mcg/kg | Lead-In Part: Percentage of Participants Testing Positive for Anti-E7777 and Anti-interleukin (IL)-2 Antibodies | Cycle 5 Day 1 (Anti-IL-2 Antibodies) | 100.0 percentage of participants |
| Lead-In Part: E7777 12 mcg/kg | Lead-In Part: Percentage of Participants Testing Positive for Anti-E7777 and Anti-interleukin (IL)-2 Antibodies | Cycle 1 Day 1 (Anti-E7777 Antibodies) | 88.9 percentage of participants |
| Lead-In Part: E7777 12 mcg/kg | Lead-In Part: Percentage of Participants Testing Positive for Anti-E7777 and Anti-interleukin (IL)-2 Antibodies | Cycle 2 Day 1 (Anti-E7777 Antibodies) | 83.3 percentage of participants |
| Lead-In Part: E7777 15 mcg/kg | Lead-In Part: Percentage of Participants Testing Positive for Anti-E7777 and Anti-interleukin (IL)-2 Antibodies | Cycle 3 Day 1 (Anti-E7777 Antibodies) | 0 percentage of participants |
| Lead-In Part: E7777 15 mcg/kg | Lead-In Part: Percentage of Participants Testing Positive for Anti-E7777 and Anti-interleukin (IL)-2 Antibodies | Cycle 5 Day 1 (Anti-E7777 Antibodies) | 0 percentage of participants |
| Lead-In Part: E7777 15 mcg/kg | Lead-In Part: Percentage of Participants Testing Positive for Anti-E7777 and Anti-interleukin (IL)-2 Antibodies | Cycle 2 Day 1 (Anti-E7777 Antibodies) | 0 percentage of participants |
| Lead-In Part: E7777 15 mcg/kg | Lead-In Part: Percentage of Participants Testing Positive for Anti-E7777 and Anti-interleukin (IL)-2 Antibodies | Cycle 1 Day 1 (Anti-E7777 Antibodies) | 100.0 percentage of participants |
| Lead-In Part: E7777 15 mcg/kg | Lead-In Part: Percentage of Participants Testing Positive for Anti-E7777 and Anti-interleukin (IL)-2 Antibodies | Cycle 1 Day 1 (Anti-IL-2 Antibodies) | 0 percentage of participants |
| Lead-In Part: E7777 15 mcg/kg | Lead-In Part: Percentage of Participants Testing Positive for Anti-E7777 and Anti-interleukin (IL)-2 Antibodies | Cycle 5 Day 1 (Anti-IL-2 Antibodies) | 0 percentage of participants |
| Lead-In Part: E7777 15 mcg/kg | Lead-In Part: Percentage of Participants Testing Positive for Anti-E7777 and Anti-interleukin (IL)-2 Antibodies | Cycle 3 Day 1 (Anti-IL-2 Antibodies) | 0 percentage of participants |
| Lead-In Part: E7777 15 mcg/kg | Lead-In Part: Percentage of Participants Testing Positive for Anti-E7777 and Anti-interleukin (IL)-2 Antibodies | Cycle 2 Day 1 (Anti-IL-2 Antibodies) | 0 percentage of participants |
Secondary
Lead-In Part: Terminal Elimination Half-life (t1/2) of E7777
Participants were not available for analysis in 15 mcg/kg (Cycles 3 and 5), 6 mcg/kg (Cycle 5), 9 mcg/kg (Cycles 3 and 5), 12 mcg/kg (Cycle 3), hence no PK data was collected and analyzed for these doses and cycles.
Time frame: Cycles 1, 3, 5 Day 1: Pre-dose up to 300 hours post-dose (Cycle length was 21 days)
Population: Lead-in PK analysis set included all participants who received at least one dose of study drug and from whom at least one valid E7777 PK parameter was obtained. Here overall number of participants analyzed signifies participants who were evaluable for this outcome measure. Here number analyzed signifies participants who were evaluable for this outcome measure for given timepoints.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Lead-In Part: E7777 6 mcg/kg | Lead-In Part: Terminal Elimination Half-life (t1/2) of E7777 | Cycle 1 Day 1 | 92.0 minutes |
| Lead-In Part: E7777 6 mcg/kg | Lead-In Part: Terminal Elimination Half-life (t1/2) of E7777 | Cycle 3 Day 1 | 39.6 minutes |
| Lead-In Part: E7777 9 mcg/kg | Lead-In Part: Terminal Elimination Half-life (t1/2) of E7777 | Cycle 1 Day 1 | 116 minutes |
| Lead-In Part: E7777 12 mcg/kg | Lead-In Part: Terminal Elimination Half-life (t1/2) of E7777 | Cycle 1 Day 1 | 100 minutes |
| Lead-In Part: E7777 12 mcg/kg | Lead-In Part: Terminal Elimination Half-life (t1/2) of E7777 | Cycle 5 Day 1 | 20.5 minutes |
| Lead-In Part: E7777 15 mcg/kg | Lead-In Part: Terminal Elimination Half-life (t1/2) of E7777 | Cycle 1 Day 1 | 100 minutes |
Secondary
Lead-In Part: Time to Reach Maximum (Peak) Concentration After Drug Administration (Tmax)
Participants were not available for analysis in 15 mcg/kg (Cycles 3 and 5), 6 mcg/kg (Cycle 5), 9 mcg/kg (Cycles 3 and 5), 12 mcg/kg (Cycle 3), hence no PK data was collected and analyzed for these doses and cycles.
Time frame: Cycles 1, 3, 5 Day 1: Pre-dose up to 300 hours post-dose (Cycle length was 21 days)
Population: Lead-in PK analysis set included all participants who received at least one dose of study drug and from whom at least one valid E7777 PK parameter was obtained. Here overall number of participants analyzed signifies participants who were evaluable for this outcome measure. Here number analyzed signifies participants who were evaluable for this outcome measure for given timepoints.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Lead-In Part: E7777 6 mcg/kg | Lead-In Part: Time to Reach Maximum (Peak) Concentration After Drug Administration (Tmax) | Cycle 1 Day 1 | 75 minute |
| Lead-In Part: E7777 6 mcg/kg | Lead-In Part: Time to Reach Maximum (Peak) Concentration After Drug Administration (Tmax) | Cycle 3 Day 1 | 60 minute |
| Lead-In Part: E7777 9 mcg/kg | Lead-In Part: Time to Reach Maximum (Peak) Concentration After Drug Administration (Tmax) | Cycle 1 Day 1 | 60 minute |
| Lead-In Part: E7777 12 mcg/kg | Lead-In Part: Time to Reach Maximum (Peak) Concentration After Drug Administration (Tmax) | Cycle 1 Day 1 | 61.5 minute |
| Lead-In Part: E7777 12 mcg/kg | Lead-In Part: Time to Reach Maximum (Peak) Concentration After Drug Administration (Tmax) | Cycle 5 Day 1 | 60 minute |
| Lead-In Part: E7777 15 mcg/kg | Lead-In Part: Time to Reach Maximum (Peak) Concentration After Drug Administration (Tmax) | Cycle 1 Day 1 | 60 minute |
Secondary
Lead-In Part: Time to Response (TTR) Per Investigator Assessment
Time to response per investigator assessment was defined as the time from date of first dose to the date of the first documented CR or PR. The tumor assessment was based on GRS Olsen 2011 criteria. CR was defined as disappearance of all evidence of disease and PR was defined as 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 (Up to 1 year 2 months)
Population: Lead-in analysis set included all participants enrolled in the Lead-in part. Here, 'overall number of participants analyzed' were those who had CR or PR in lead-in part of the study.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Lead-In Part: E7777 6 mcg/kg | Lead-In Part: Time to Response (TTR) Per Investigator Assessment | 106.0 days |
| Lead-In Part: E7777 9 mcg/kg | Lead-In Part: Time to Response (TTR) Per Investigator Assessment | 53.5 days |
| Lead-In Part: E7777 12 mcg/kg | Lead-In Part: Time to Response (TTR) Per Investigator Assessment | 64.0 days |
Secondary
Lead-In Part: Total Body Clearance (CL) of E7777
Participants were not available for analysis in 15 mcg/kg (Cycles 3 and 5), 6 mcg/kg (Cycle 5), 9 mcg/kg (Cycles 3 and 5), 12 mcg/kg (Cycle 3), hence no PK data was collected and analyzed for these doses and cycles. Here, mL/min/kg means milliliter per minute per kilogram.
Time frame: Cycles 1, 3, 5 Day 1: Pre-dose up to 300 hours post-dose (Cycle length was 21 days)
Population: Lead-in PK analysis set included all participants who received at least one dose of study drug and from whom at least one valid E7777 PK parameter was obtained. Here overall number of participants analyzed signifies participants who were evaluable for this outcome measure. Here number analyzed signifies participants who were evaluable for this outcome measure for given timepoints.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Lead-In Part: E7777 6 mcg/kg | Lead-In Part: Total Body Clearance (CL) of E7777 | Cycle 1 Day 1 | 0.316 mL/min/kg | Standard Deviation 0.12 |
| Lead-In Part: E7777 6 mcg/kg | Lead-In Part: Total Body Clearance (CL) of E7777 | Cycle 3 Day 1 | 1.21 mL/min/kg | — |
| Lead-In Part: E7777 9 mcg/kg | Lead-In Part: Total Body Clearance (CL) of E7777 | Cycle 1 Day 1 | 0.492 mL/min/kg | Standard Deviation 0.38 |
| Lead-In Part: E7777 12 mcg/kg | Lead-In Part: Total Body Clearance (CL) of E7777 | Cycle 1 Day 1 | 0.551 mL/min/kg | Standard Deviation 0.48 |
| Lead-In Part: E7777 12 mcg/kg | Lead-In Part: Total Body Clearance (CL) of E7777 | Cycle 5 Day 1 | 1.80 mL/min/kg | — |
| Lead-In Part: E7777 15 mcg/kg | Lead-In Part: Total Body Clearance (CL) of E7777 | Cycle 1 Day 1 | 0.359 mL/min/kg | — |
Secondary
Lead-In Part: Volume of Distribution at Steady State (Vdss) of E7777
Participants were not available for analysis in 15 mcg/kg (Cycles 3 and 5), 6 mcg/kg (Cycle 5), 9 mcg/kg (Cycles 3 and 5), 12 mcg/kg (Cycle 3), hence no PK data was collected and analyzed for these doses and cycles.
Time frame: Cycles 1, 3, 5 Day 1: Pre-dose up to 300 hours post-dose (Cycle length was 21 days)
Population: Lead-in PK analysis set included all participants who received at least one dose of study drug and from whom at least one valid E7777 PK parameter was obtained. Here overall number of participants analyzed signifies participants who were evaluable for this outcome measure. Here number analyzed signifies participants who were evaluable for this outcome measure for given timepoints.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Lead-In Part: E7777 6 mcg/kg | Lead-In Part: Volume of Distribution at Steady State (Vdss) of E7777 | Cycle 1 Day 1 | 39.8 milliliter per kilogram (mL/kg) | Standard Deviation 4.81 |
| Lead-In Part: E7777 6 mcg/kg | Lead-In Part: Volume of Distribution at Steady State (Vdss) of E7777 | Cycle 3 Day 1 | 69.1 milliliter per kilogram (mL/kg) | — |
| Lead-In Part: E7777 9 mcg/kg | Lead-In Part: Volume of Distribution at Steady State (Vdss) of E7777 | Cycle 1 Day 1 | 60.3 milliliter per kilogram (mL/kg) | Standard Deviation 19.5 |
| Lead-In Part: E7777 12 mcg/kg | Lead-In Part: Volume of Distribution at Steady State (Vdss) of E7777 | Cycle 1 Day 1 | 61 milliliter per kilogram (mL/kg) | Standard Deviation 21.8 |
| Lead-In Part: E7777 12 mcg/kg | Lead-In Part: Volume of Distribution at Steady State (Vdss) of E7777 | Cycle 5 Day 1 | 53.3 milliliter per kilogram (mL/kg) | — |
| Lead-In Part: E7777 15 mcg/kg | Lead-In Part: Volume of Distribution at Steady State (Vdss) of E7777 | Cycle 1 Day 1 | 37 milliliter per kilogram (mL/kg) | — |
Secondary
Main Study Part: Area Under the Curve From Time 0 to Time Infinity (AUC[0-inf]) of E7777
Participants were not available for analysis at Cycle 3 Day 1, hence no PK data was collected and analyzed for this timepoint.
Time frame: Cycles 1, 3 and 5 Day 1: Pre-dose up to 300 hours post-dose (Cycle length was 21 days)
Population: Main study part PK analysis set included all participants from whom at least one quantifiable concentration of E7777 was observed at 9 mcg/kg dose (both Main Study and Lead-In). Here overall number of participants analyzed signifies participants who were evaluable for this outcome measure. Here number analyzed signifies participants who were evaluable for this outcome measure at given time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Lead-In Part: E7777 6 mcg/kg | Main Study Part: Area Under the Curve From Time 0 to Time Infinity (AUC[0-inf]) of E7777 | Cycle 1 Day 1 | 23700 min*ng/mL | Standard Deviation 12700 |
| Lead-In Part: E7777 6 mcg/kg | Main Study Part: Area Under the Curve From Time 0 to Time Infinity (AUC[0-inf]) of E7777 | Cycle 5 Day 1 | 4630 min*ng/mL | — |
Secondary
Main Study Part: Area Under the Curve From Time 0 to Time t (AUC[0-t]) of E7777
Time frame: Cycles 1, 3 and 5 Day 1: Pre-dose up to 300 hours post-dose (Cycle length was 21 days)
Population: Main study part PK analysis set included all participants from whom at least one quantifiable concentration of E7777 was observed at 9 mcg/kg dose (both Main Study and Lead-In). Here overall number of participants analyzed signifies participants who were evaluable for this outcome measure. Here number analyzed signifies participants who were evaluable for this outcome measure at given time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Lead-In Part: E7777 6 mcg/kg | Main Study Part: Area Under the Curve From Time 0 to Time t (AUC[0-t]) of E7777 | Cycle 1 Day 1 | 16300 min*ng/mL | Standard Deviation 12600 |
| Lead-In Part: E7777 6 mcg/kg | Main Study Part: Area Under the Curve From Time 0 to Time t (AUC[0-t]) of E7777 | Cycle 3 Day 1 | 2170 min*ng/mL | Standard Deviation 974 |
| Lead-In Part: E7777 6 mcg/kg | Main Study Part: Area Under the Curve From Time 0 to Time t (AUC[0-t]) of E7777 | Cycle 5 Day 1 | 2660 min*ng/mL | Standard Deviation 2570 |
Secondary
Main Study Part: Duration of Response (DOR) Per Independent Review Committee
DOR per independent review committee was defined as the time from the date when criteria for response (CR or PR) was first met until the date of the first documentation of PD or date of death from any cause. The tumor assessment was based on GRS Olsen 2011 criteria. CR was defined as disappearance of all evidence of disease and PR was defined as regression of measurable disease and no new sites. PD was defined as any new lesion or unequivocally increase of previously involved sites from nadir.
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 (Up to 3 years 6 months)
Population: Primary efficacy analysis set included all participants with Stages I to III CTCL (both Main Study and Lead-In part) who received study drug at the 9 mcg/kg dose. Here, 'overall number of participants analyzed' were those who had CR or PR in Lead-in part and in Main study part.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Lead-In Part: E7777 6 mcg/kg | Main Study Part: Duration of Response (DOR) Per Independent Review Committee | 6.47 months |
Secondary
Main Study Part: Duration of Skin Response
The duration of skin response based on the mSWAT score was defined as time from the date when criteria for skin response (CR or PR) was first met until the date of documented PD or death due to any cause for those participants with a confirmed PR or CR. mSWAT was used to measure skin disease severity based on the percentage of BSA with patches, plaques, or tumors. Total scores were calculated by multiplying the BSA percentage for each category of lesion (patch, plaque, or tumor) by a weighting factor and adding the three sub-scores which ranged from 0 (unaffected) to 400 (severely affected). Lower scores indicated a lower degree of skin disease severity. CR corresponded to 100% clearance of skin lesions present at baseline (mSWAT score of 0). PR corresponded to 50-99% clearance of skin disease present at baseline (at least 50% reduction in mSWAT score), without new tumors.
Time frame: Up to 30 months
Population: Primary efficacy analysis set included all participants with Stages I to III CTCL (both Main Study and Lead-In part) who received study drug at the 9 mcg/kg dose. Here 'overall number of participants analyzed' were those who had a skin response.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Lead-In Part: E7777 6 mcg/kg | Main Study Part: Duration of Skin Response | 6.47 months |
Secondary
Main Study Part: Maximum Serum Concentration (Cmax) of E7777
Time frame: Cycles 1, 3 and 5 Day 1: Pre-dose up to 300 minutes post-dose (Cycle length was 21 days)
Population: Main study part PK analysis set included all participants from whom at least one quantifiable concentration of E7777 was observed at 9 mcg/kg dose (both Main Study and Lead-In). Here overall number of participants analyzed signifies participants who were evaluable for this outcome measure. Here number analyzed signifies participants who were evaluable for this outcome measure at given timepoints.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Lead-In Part: E7777 6 mcg/kg | Main Study Part: Maximum Serum Concentration (Cmax) of E7777 | Cycle 1 Day 1 | 114 ng/mL | Standard Deviation 62.5 |
| Lead-In Part: E7777 6 mcg/kg | Main Study Part: Maximum Serum Concentration (Cmax) of E7777 | Cycle 3 Day 1 | 37.5 ng/mL | Standard Deviation 19.4 |
| Lead-In Part: E7777 6 mcg/kg | Main Study Part: Maximum Serum Concentration (Cmax) of E7777 | Cycle 5 Day 1 | 45.5 ng/mL | Standard Deviation 46.8 |
Secondary
Main Study Part: Number of Participants With Objective Skin Response
Modified severity weighted assessment tool (mSWAT) was used to measure skin disease severity based on the percentage of body surface area (BSA) with patches, plaques, or tumors. Total scores were calculated by multiplying the BSA percentage for each category of lesion (patch, plaque, or tumor) by a weighting factor and adding the three sub-scores which ranged from 0 (unaffected) to 400 (severely affected). Lower scores indicated a lower degree of skin disease severity. CR corresponded to 100% clearance of skin lesions present at baseline (mSWAT score of 0). PR corresponded to 50-99% clearance of skin disease present at baseline (at least 50% reduction in mSWAT score), without new tumors.
Time frame: Up to 30 months
Population: Primary efficacy analysis set included all participants with Stages I to III CTCL (both Main Study and Lead-In part) who received study drug at the 9 mcg/kg dose.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Lead-In Part: E7777 6 mcg/kg | Main Study Part: Number of Participants With Objective Skin Response | 25 Participants |
Secondary
Main Study Part: ORR Per IRC Based on Prince 2010 Criteria
ORR was defined as the percentage of participants whose BOR was CR, clinical complete response (CCR) or PR per IRC. The tumor response was based on Prince 2010 criteria. CR was defined as disappearance of all evidence of disease and PR was defined as regression of measurable disease and no new sites. CCR was defined as tumor residue not visible on esophagogram, computed tomography (CT), endoscopy, positron emission tomography (PET)-CT.
Time frame: From the date of administration of the first dose of the study drug until disease progression (Up to 3 years 6 months)
Population: Primary efficacy analysis set included all participants with Stages I to III CTCL (both Main Study and Lead-In part) who received study drug at the 9 mcg/kg dose.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Lead-In Part: E7777 6 mcg/kg | Main Study Part: ORR Per IRC Based on Prince 2010 Criteria | 36.2 percentage of participants |
Secondary
Main Study Part: Percentage of Participants Testing Positive for Anti-E7777 and Anti-IL-2 Antibodies
Immunogenicity was assessed by determining the anti-E7777 and anti-IL-2 antibodies in serum using validated methods. Percentage of participants testing positive for Anti-E7777 and Anti-IL-2 antibodies were reported.
Time frame: Cycle 1 Day 1, Cycle 2 Day 1, Cycle 3 Day 1
Population: Main Study Part PK Analysis Set included all participants from whom at least one quantifiable concentration of E7777 was observed at 9 mcg/kg dose (both Main Study and Lead-In).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Lead-In Part: E7777 6 mcg/kg | Main Study Part: Percentage of Participants Testing Positive for Anti-E7777 and Anti-IL-2 Antibodies | Cycle 1 Day 1 (Anti-E7777 Antibodies) | 85.7 percentage of participants |
| Lead-In Part: E7777 6 mcg/kg | Main Study Part: Percentage of Participants Testing Positive for Anti-E7777 and Anti-IL-2 Antibodies | Cycle 2 Day 1 (Anti-E7777 Antibodies) | 91.7 percentage of participants |
| Lead-In Part: E7777 6 mcg/kg | Main Study Part: Percentage of Participants Testing Positive for Anti-E7777 and Anti-IL-2 Antibodies | Cycle 3 Day 1 (Anti-E7777 Antibodies) | 95.7 percentage of participants |
| Lead-In Part: E7777 6 mcg/kg | Main Study Part: Percentage of Participants Testing Positive for Anti-E7777 and Anti-IL-2 Antibodies | Cycle 1 Day 1 (Anti-IL-2 Antibodies) | 5.5 percentage of participants |
| Lead-In Part: E7777 6 mcg/kg | Main Study Part: Percentage of Participants Testing Positive for Anti-E7777 and Anti-IL-2 Antibodies | Cycle 2 Day 1 (Anti-IL-2 Antibodies) | 52.3 percentage of participants |
| Lead-In Part: E7777 6 mcg/kg | Main Study Part: Percentage of Participants Testing Positive for Anti-E7777 and Anti-IL-2 Antibodies | Cycle 3 Day 1 (Anti-IL-2 Antibodies) | 88.6 percentage of participants |
Secondary
Main Study Part: Terminal Elimination Half-life (t1/2) of E7777
Time frame: Cycles 1, 3 and 5 Day 1: Pre-dose up to 300 hours post-dose (Cycle length was 21 days)
Population: Main study part PK analysis set included all participants from whom at least one quantifiable concentration of E7777 was observed at 9 mcg/kg dose (both Main Study and Lead-In). Here overall number of participants analyzed signifies participants who were evaluable for this outcome measure. Here number analyzed signifies participants who were evaluable for this outcome measure at given time points.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Lead-In Part: E7777 6 mcg/kg | Main Study Part: Terminal Elimination Half-life (t1/2) of E7777 | Cycle 1 Day 1 | 109 minutes |
| Lead-In Part: E7777 6 mcg/kg | Main Study Part: Terminal Elimination Half-life (t1/2) of E7777 | Cycle 3 Day 1 | 90.8 minutes |
| Lead-In Part: E7777 6 mcg/kg | Main Study Part: Terminal Elimination Half-life (t1/2) of E7777 | Cycle 5 Day 1 | 51.7 minutes |
Secondary
Main Study Part: Time to Reach Maximum (Peak) Concentration After Drug Administration (Tmax)
Time frame: Cycles 1, 3 and 5 Day 1: Pre-dose up to 300 hours post-dose (Cycle length was 21 days)
Population: Main study part PK analysis set included all participants from whom at least one quantifiable concentration of E7777 was observed at 9 mcg/kg dose (both Main Study and Lead-In). Here overall number of participants analyzed signifies participants who were evaluable for this outcome measure. Here number analyzed signifies participants who were evaluable for this outcome measure at given time points.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Lead-In Part: E7777 6 mcg/kg | Main Study Part: Time to Reach Maximum (Peak) Concentration After Drug Administration (Tmax) | Cycle 1 Day 1 | 60 minutes |
| Lead-In Part: E7777 6 mcg/kg | Main Study Part: Time to Reach Maximum (Peak) Concentration After Drug Administration (Tmax) | Cycle 3 Day 1 | 60 minutes |
| Lead-In Part: E7777 6 mcg/kg | Main Study Part: Time to Reach Maximum (Peak) Concentration After Drug Administration (Tmax) | Cycle 5 Day 1 | 60 minutes |
Secondary
Main Study Part: Time to Response (TTR) Per Independent Review Committee
Time to response per independent review committee was defined as the time from date of first dose to the date of the first documented CR or PR. The tumor assessment was based on GRS Olsen 2011 criteria. CR was defined as disappearance of all evidence of disease and PR was defined as 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 (Up to 3 years 6 months)
Population: Primary efficacy analysis set included all participants with Stages I to III CTCL (both Main Study and Lead-In part) who received study drug at the 9 mcg/kg dose. Here, 'overall number of participants analyzed' were those who had CR or PR in Lead-in part and in Main study part.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Lead-In Part: E7777 6 mcg/kg | Main Study Part: Time to Response (TTR) Per Independent Review Committee | 1.41 months |
Secondary
Main Study Part: Time to Skin Response
The time to skin response based on the mSWAT score was defined as time from the date of first dose to the date when criteria for skin response (CR or PR) were first met. mSWAT was used to measure skin disease severity based on the percentage of BSA with patches, plaques, or tumors. Total scores were calculated by multiplying the BSA percentage for each category of lesion (patch, plaque, or tumor) by a weighting factor and adding the three sub-scores which ranged from 0 (unaffected) to 400 (severely affected). Lower scores indicated a lower degree of skin disease severity. CR corresponded to 100% clearance of skin lesions present at baseline (mSWAT score of 0). PR corresponded to 50-99% clearance of skin disease present at baseline (at least 50% reduction in mSWAT score), without new tumors.
Time frame: Up to 30 months
Population: Primary efficacy analysis set included all participants with Stages I to III CTCL (both Main Study and Lead-In part) who received study drug at the 9 mcg/kg dose. Here 'overall number of participants analyzed' were those who had a skin response.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Lead-In Part: E7777 6 mcg/kg | Main Study Part: Time to Skin Response | 1.41 months |
Secondary
Main Study Part: Total Body Clearance (CL) of E7777
Participants were not available for analysis at Cycle 3 Day 1, hence no PK data was collected and analyzed for this timepoint.
Time frame: Cycles 1, 3 and 5 Day 1: Pre-dose up to 300 hours post-dose (Cycle length was 21 days)
Population: Main study part PK analysis set included all participants from whom at least one quantifiable concentration of E7777 was observed at 9 mcg/kg dose (both Main Study and Lead-In). Here overall number of participants analyzed signifies participants who were evaluable for this outcome measure. Here number analyzed signifies participants who were evaluable for this outcome measure for given time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Lead-In Part: E7777 6 mcg/kg | Main Study Part: Total Body Clearance (CL) of E7777 | Cycle 1 Day 1 | 44.6 mL/min/kg | Standard Deviation 32.6 |
| Lead-In Part: E7777 6 mcg/kg | Main Study Part: Total Body Clearance (CL) of E7777 | Cycle 5 Day 1 | 133 mL/min/kg | — |
Secondary
Main Study Part: Volume of Distribution at Steady State (Vdss) of E7777
Participants were not available for analysis at Cycle 3 Day 1, hence no PK data was collected and analyzed for this timepoint.
Time frame: Cycles 1, 3 and 5 Day 1: Pre-dose up to 300 hours post-dose (Cycle length was 21 days)
Population: Main study part PK analysis set included all participants from whom at least one quantifiable concentration of E7777 was observed at 9 mcg/kg dose (both Main Study and Lead-In). Here overall number of participants analyzed signifies participants who were evaluable for this outcome measure. Here number analyzed signifies participants who were evaluable for this outcome measure for given time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Lead-In Part: E7777 6 mcg/kg | Main Study Part: Volume of Distribution at Steady State (Vdss) of E7777 | Cycle 1 Day 1 | 5430 milliliter (mL) | Standard Deviation 2210 |
| Lead-In Part: E7777 6 mcg/kg | Main Study Part: Volume of Distribution at Steady State (Vdss) of E7777 | Cycle 5 Day 1 | 10700 milliliter (mL) | — |