Efficacy and Safety of Oral HBI-8000 in Patients With Relapsed or Refractory Peripheral T-cell Lymphoma (PTCL)

Tumor assessment was performed every 8 weeks until disease progression. Objective response rate was defined as the percentage of patients who achieved a complete response (CR) or a partial response (PR) according to International Workshop Response Criteria (IWC) 2014 criteria and assessed by an Independent Overall Efficacy Review Committee (IOERC). CR: Target nodes/nodal masses must regress to \<1.5 cm in longest transverse diameter of a lesion (LDi), no extralymphatic sites of disease, nonmeasured lesion is absent, disappearance of spleen or liver enlargement, no new lesions, no bone marrow (BM) involvement. PR: ≥50% decrease in sum of the product of the perpendicular diameters for multiple lesions (SPD) of up to 6 target measurable nodes and extranodal sites, nonmeasured lesions is absent/normal, regressed, but no increase, spleen must have regressed by \>50% in length beyond normal, no new lesions.

Time frame: Up to approximately 47 months.

Population: The per-protocol analysis set (PPS) included subjects meeting all eligibility criteria who have completed Cycle 1 treatment. For subjects who developed clinical PD and discontinued study treatment during Cycle 1 without significant deviation from protocol, they will be included in the PPS. It should be noted that the PPS includes subjects who discontinued within Cycle 1 due to clinical PD without imaging studies to assess disease status.

PFS was defined as the duration from the date of the first study drug dose to the disease progression or death, whichever occurs first. PD was defined using the IWC 2014 criteria, as any new lesion or an individual node/lesion must be abnormal with: LDi \>1.5 cm and increase by 50% from perpendicular diameters nadir and an increase in LDi or shortest axis perpendicular to the LDi from nadir, 0.5 cm for lesions \<2 cm or 1.0 cm for lesions \>2 cm.

Time frame: Up to approximately 47 months.

Population: PPS

DOR was defined as the duration of response from first response (CR/PR) to disease progression or death, whichever occurs first. CR or PR according to the IWC 2014 criteria was assessed by an IOERC.

Time frame: Up to approximately 47 months.

Population: Subjects who achieved PR or CR in the PPS

Tumor assessment was performed every 8 weeks until disease progression. Objective response rate was defined as the percentage of patients who achieved a CR or a PR according to IWC 2014 criteria and assessed by an IOERC. CR: Target nodes/nodal masses must regress to \<1.5 cm in LDi, no extralymphatic sites of disease, nonmeasured lesion is absent, disappearance of spleen or liver enlargement, no new lesions, no BM involvement. PR: ≥50% decrease in SPD of up to 6 target measurable nodes and extranodal sites, nonmeasured lesions is absent/normal, regressed, but no increase, spleen must have regressed by \>50% in length beyond normal, no new lesions. Disease subtype (PTCL-NOS, AITL, ALCL, ALK, EATL) was assessed by Central Pathology Review (CPR).

Time frame: Up to approximately 47 months.

Population: PPS \[Per Protocol Set\]

Safety evaluated as number of participants with treatment-related adverse events as assessed by CTCAE v4.0. From date of first study drug to 30±3 days after the last dosing of the study drug or before the initiation of new cancer treatment.

Time frame: Up to approximately 44 months.

Population: Safety analysis set (SAF) includes all subjects who received at least one dose of HBI 8000.

Overall survival is defined as the duration from the first dose of study medication to death from any cause.

Time frame: Up to approximately 55 months.

Population: PPS - Per Protocol Set

Area under the plasma concentration time curve from zero (predose) extrapolated to infinity (ng\*h/mL) (Day 1 only), calculated by linear up/log down trapezoidal summation and extrapolated to infinity by addition of the last quantifiable concentration (Clast) divided by the apparent terminal rate constant (λz): AUC(0-last) + Clast/λz. Calculated for the C1D1 dose only.

Time frame: 0 (predose) up to 72 hours postdose on C1D1

Population: PK population includes all subjects, at the selected sites in Japan and all sites in South Korea, who have pretreatment baseline and at least 1 blood sample on study providing PK data for HBI-8000.

Area under the plasma concentration time curve over the dosing interval tau (ng\*h/mL), calculated by linear up/log down trapezoidal summation. Calculated for the C1D1 dose only. Actual elapsed sampling time at tau and the corresponding plasma concentration was used in the calculation of this parameter. If concentrations fall to BLQ before or at tau, AUCall (area under the plasma concentration time curve from zero \[predose\] to the time of the last observation within the dosing interval, calculated by linear up/log down trapezoidal summation) was used as the estimate of this parameter.

Time frame: 0 (predose) up to 72 hours postdose on C1D1

Population: PK population includes all subjects, at the selected sites in Japan and all sites in South Korea, who have pretreatment baseline and at least 1 blood sample on study providing PK data for HBI-8000.

Maximum observed plasma concentration (ng/mL), obtained directly from the observed concentration versus time data. Calculated for the C1D1 and C2D1 doses.

Time frame: 0 (predose) up to 72 hours postdose on C1D1 and 0 (predose) up to 4 hours postdose on C2D1

Population: PK population includes all subjects, at the selected sites in Japan and all sites in South Korea, who have pretreatment baseline and at least 1 blood sample on study providing PK data for HBI-8000.

Apparent terminal half-life (h), calculated as (ln 2)/λz. Calculated for the C1D1 dose only.

Time frame: 0 (predose) up to 72 hours postdose on C1D1

Population: PK population includes all subjects, at the selected sites in Japan and all sites in South Korea, who have pretreatment baseline and at least 1 blood sample on study providing PK data for HBI-8000.