study to evaluate efficacy and safety of hh2853 in relapsed/refractory peripheral t-cell lymphoma

Conditions: Relapsed/Refractory Peripheral T-Cell Lymphoma (R/R PTCL)

Summary: this study is a an open-label, multinational, multicenter, single-arm phase ⅰb/ⅱ study to evaluate efficacy and safety of oral hh2853 in patients with relapsed/refractory peripheral t-cell lymphoma.

this study includes phase ib and phase ii. in the phase ib, patients with r/r nhl (dose escalation) or r/r ptcl (dose expansion) who have received at least 1 line of prior systematic treatment and meet the inclusion/exclusion criteria in the protocol will be enrolled. safety run-in study (japan only): the objective of the safety run-in study in japan is to evaluate the safety, tolerability, and pk profile of hh2853 in japanese patients. the primary objective of the phase ib study is to determine the rp2d of hh2853 in ptcl patients. the secondary objectives are to evaluate the safety, preliminary efficacy and characterize the pharmacokinetic profile of hh2853 in r/r ptcl patients. a "3+3" design will be used in the dose escalation part with a starting dose of 400 mg bid. based on the safety, efficacy and pk/pd data and hh2853-g101 data, 1-2 dose levels could be expanded, 10-15 r/r ptcl patients for each dose level. approximately 21-48 patients will be enrolled in total. in the phase ii (multi-national): patients with r/r ptcl who have received at least one prior systemic combination chemotherapy and at least one new drug therapy and meet the inclusion/exclusion criteria in the protocol will be enrolled. the phase ii study will be started once the rp2d is determined. the phase ii study is a single-arm study and will be enrolled in approximately 66 efficacy-evaluable r/r ptcl patients who had received at least one prior systemic combination chemotherapy and at least one new drug therapy. the primary objective of the phase ii study is to evaluate the efficacy of hh2853 of r/r ptcl patients who have received at least one prior systemic combination chemotherapy and at least one new drug therapy (orr, birc evaluation); the secondary objectives will be continued to further evaluate the efficacy, safety, tolerability and pk characteristics of hh2853 of r/r ptcl patients who have received at least 1 line of prior systemic therapy.

Eligibility criteria:
inclusion criteria: * main inclusion: 1. tumor types and prior antitumor therapy: phase ib:dose escalation: all enrolled patients must have histologically confirmed diagnosis nhl who have received at least one line of prior systematic treatment (and ≤ 5 lines) and relapses or refractory. phase ib dose expansion part: all enrolled patients must have histologically confirmed diagnosis of ptcl, including subtypes: ptcl-nos, aitl, alk + alcl, alk-alcl, nktcl, enteropathy associated t-cell lymphoma (eatl), monomorphic epitheliotropic internal t-cell lymphoma (meitl), hepatosplenic t-cell lymphoma (hstcl), follicular t-cell lymphoma (ftcl), nodal peripheral t-cell lymphoma with tfh phenotype (nodal ptcl-tfh) and other invasive t-cell sources nhl at the investigator and sponsor's discretion (except highly invasive). all enrolled patients had relapsed or refractory diseases after receiving 1-line systematic treatment (≤ 3 lines). phase ii: all enrolled patients must have histologically confirmed diagnosis of ptcl, including subtypes: ptcl-nos, aitl, alk+alcl, alk-alcl, nktcl, eatl, meitl, hstcl, ftcl, nodal ptcl-tfh et al. patients must have histologically confirmed diagnosis of r/r ptcl who have received at least one line of prior systematic combination chemotherapy and at least one new drug therapy (prior antitumor treatment lines ≤4 lines) : relapse and/or refractory. 2. availability of qualified tissue samples by patient for pathological diagnosis by the central laboratory. 3. the eastern cooperative oncology group (ecog) score 0-1. 4. life expectancy ≥ 3 months before starting hh2853 treatment. 5. sufficient bone marrow, liver and renal functions. exclusion criteria: * main criteria: 1. previous treatment with ezh2 or ezh1/2 inhibitors. 2. central nervous system invasion. 3. any previous history of bone marrow malignancy, including myelodysplastic syndrome (mds). 4. received medications that are known potent cyp3a4 inducers/inhibitors within 1 week prior to first dose.

Keywords: relapsed/refractory peripheral t-cell lymphoma