E7777 for the Treatment of Patients With Peripheral T-Cell Lymphoma

The MTD was defined as the maximum tolerated dose observed after the evaluation of dose limiting toxicity (DLT) in Cycle 1 with 6 participants. If it was judged that the dose was not tolerated and DLT was confirmed in only 3 participants in the lower dose cohort, 3 other participants were to be added and tolerability was evaluated with 6 participants in total. The RD was to be comprehensively determined based on the MTD and safety data. Participants not evaluable for DLT were defined as participants found to be ineligible or in whom DLT evaluation was impossible due to premature termination for reasons other than toxicities in the judgement of the Sponsor, among those who had received at least one dose of the investigational drug after enrollment.

Safety assessments consisted of monitoring and recording all AEs and SAEs; regular monitoring of hematology, blood coagulation, blood chemistry, and urinalysis values; periodic measurement of vital signs, body weight, 12-lead electrocardiograms (ECGs), Eastern Cooperative Oncology Group performance status, physical examination findings, and ophthalmological examination findings. TEAEs were defined as an AE that had an onset date, or worsening in severity from baseline (pre-treatment), on or after the first dose of study drug up to the last assessment. Treatment-related TEAEs included TEAEs that were considered by the investigator to be possibly or probably related to study drug. SAEs were defined as any untoward medical occurrence which results in death, was life-threatening, required hospitalization or prolonged hospitalization, resulted in persistent or significant disability/incapacity, or caused a congenital anomaly/birth defect.

Cmax was defined as the maximum observed concentration of denileukin diftitox following administration of study treatment on Cycle 1 Day 1 and was obtained directly from the measured serum concentration-time curves. Blood samples were collected before and 30 minutes after the start of infusion and immediately (0 minutes), 30, 60, 90, and 120 minutes after the end of infusion of denileukin diftitox. The samples were analyzed for the amount of denileukin diftitox in the serum using a validated ligand-binding assay with a lower limit of quantitation (LLOQ) of 30 nanograms per milliliter (ng/mL). Serum pharmacokinetic (PK) data were analyzed using a non-compartmental analysis approach to obtain individual participant estimates of Cmax, which was then summarized as the median and full range for all participants and expressed as ng/mL.

Blood samples were collected before and 30 minutes after the start of infusion and immediately (0 minutes), 30, 60, 90, and 120 minutes after the end of infusion of denileukin diftitox. The samples were analyzed for the amount of denileukin diftitox in the serum using a validated ligand-binding assay with a LLOQ of 30 ng/mL. Serum PK data were analyzed using a non-compartmental analysis approach to obtain individual participant estimates of Tmax, which was then summarized as the median and full range for all participants and expressed in minutes.

Blood samples were collected before and 30 minutes after the start of infusion and immediately (0 minutes), 30, 60, 90, and 120 minutes after the end of infusion of denileukin diftitox. The samples were analyzed for the amount of denileukin diftitox in the serum using a validated ligand-binding assay with a LLOQ of 30 ng/mL. Serum PK data were analyzed using a non-compartmental analysis approach to obtain individual participant estimates of AUC(0-t), which was then summarized as the median and full range for all participants and expressed as nanograms*minutes per milliliter (ng*min/mL).

Blood samples were collected before and 30 minutes after the start of infusion and immediately (0 minutes), 30, 60, 90, and 120 minutes after the end of infusion of denileukin diftitox. The samples were analyzed for the amount of denileukin diftitox in the serum using a validated ligand-binding assay with a LLOQ of 30 ng/mL. Serum PK data were analyzed using a non-compartmental analysis approach to obtain individual participant estimates of AUC(0-inf), which was then summarized as the median and full range for all participants and expressed as ng*min/mL.

Blood samples were collected before and 30 minutes after the start of infusion and immediately (0 minutes), 30, 60, 90, and 120 minutes after the end of infusion of denileukin diftitox. The samples were analyzed for the amount of denileukin diftitox in the serum using a validated ligand-binding assay with a LLOQ of 30 ng/mL. Serum PK data were analyzed using a non-compartmental analysis approach to obtain individual participant estimates of λz, which was then summarized as the median and full range for all participants and expressed in 1/minutes.

Blood samples were collected before and 30 minutes after the start of infusion and immediately (0 minutes), 30, 60, 90, and 120 minutes after the end of infusion of denileukin diftitox. The samples were analyzed for the amount of denileukin diftitox in the serum using a validated ligand-binding assay with a LLOQ of 30 ng/mL. Serum PK data were analyzed using a non-compartmental analysis approach to obtain individual participant estimates of t1/2, which was then summarized as the median and full range for all participants and expressed in minutes.

Blood samples were collected before and 30 minutes after the start of infusion and immediately (0 minutes), 30, 60, 90, and 120 minutes after the end of infusion of denileukin diftitox. The samples were analyzed for the amount of denileukin diftitox in the serum using a validated ligand-binding assay with a LLOQ of 30 ng/mL. Serum PK data were analyzed using a non-compartmental analysis approach to obtain individual participant estimates of Vz, which was then summarized as the median and full range for all participants and expressed as milliliters per kilogram (mL/kg).

Blood samples were collected before and 30 minutes after the start of infusion and immediately (0 minutes), 30, 60, 90, and 120 minutes after the end of infusion of denileukin diftitox. The samples were analyzed for the amount of denileukin diftitox in the serum using a validated ligand-binding assay with a LLOQ of 30 ng/mL. Serum PK data were analyzed using a non-compartmental analysis approach to obtain individual participant estimates of Vss, which was then summarized as the median and full range for all participants and expressed as mL/kg.

Blood samples were collected before and 30 minutes after the start of infusion and immediately (0 minutes), 30, 60, 90, and 120 minutes after the end of infusion of denileukin diftitox. The samples were analyzed for the amount of denileukin diftitox in the serum using a validated ligand-binding assay with a LLOQ of 30 ng/mL. SerumPK data were analyzed using a non-compartmental analysis approach to obtain individual participant estimates of CL, which was then summarized as the median and full range for all participants and expressed as milliliters/minutes/kilograms (mL/min/kg).

This endpoint was combined with primary outcome measure, MTD