An Open-label, Multinational, Multicenter, Single-arm Phase Ⅰb/Ⅱ Study to Evaluate Efficacy and Safety of Oral HH2853, a Selective EZH1/2 Inhibitor, in Patients With Relapsed/Refractory Peripheral T-cell Lymphoma
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 100
- 试验地点
- 1
- 主要终点
- Phase Ib: To determine the RP2D of HH2853 in PTCL patients
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •main inclusion:
- •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.
- •Availability of qualified tissue samples by patient for pathological diagnosis by the central laboratory.
- •The Eastern cooperative oncology group (ECOG) score 0-
- •Life expectancy ≥ 3 months before starting HH2853 treatment.
- •Sufficient bone marrow, liver and renal functions.
排除标准
- •main criteria:
- •Previous treatment with EZH2 or EZH1/2 inhibitors.
- •Central nervous system invasion.
- •Any previous history of bone marrow malignancy, including myelodysplastic syndrome (MDS).
- •Received medications that are known potent CYP3A4 inducers/inhibitors within 1 week prior to first dose.
研究组 & 干预措施
Dose escalation and expansion study of HH2853
To determine the RP2D of HH2853 in PTCL patients.
干预措施: HH2853 Tablets (Drug)
结局指标
主要结局
Phase Ib: To determine the RP2D of HH2853 in PTCL patients
时间窗: 28-day treatment cycles
Determine RP2D of HH2853
Phase II: 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
时间窗: 28-day treatment cycles
ORR will be based on the blinded independent review committee (BIRC). Assessment of oncologic response will be performed according to the 2014 edition of the Lugano Criteria for Efficacy \[Lugano\]
次要结局
- Phase Ib: 1. Preliminary efficacy of HH2853 in R/R PTCL patients;(28-day treatment cycles)
- Phase Ib: 2.To characterize the pharmacokinetic profile of HH2853(28-day treatment cycles)
- Phase II: 1.To further assess the other efficacy of HH2853 of R/R PTCL patients who have received at least one prior systemic combination chemotherapy and at least one new drug (such as Chidamide, Pralatrexate and Brentuximab vedotin, et al.) therapy(28-day treatment cycles)
- Phase II: 2. To evaluate the safety and tolerability of HH2853(28-day treatment cycles)
- Phase II: 3. To characterize the population pharmacokinetic profile of HH2853(28-day treatment cycles)