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| Name | Class |
|---|---|
| Peking University Cancer Hospital & Institute | OTHER |
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This is a Phase 1 multicenter, single-arm, open-label, dose escalation and dose expansion study of enhancer of zeste homolog 2 (EZH2 ) inhibitor SHR2554.
This study will assess the tolerability, safety, pharmacokinetics, and preliminary anti-tumor activity of SHR2554 in participants with relapsed or refractory mature lymphoid neoplasms in part I, and the the efficacy in PTCL patients will be studied in Part II.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| SHR2554 treated group | Experimental | Part I:treated with escalated doses of EZH2 inhibitor SHR2554 respectively; Part II:treated with fixed dose (RP2D) SHR2554 respectively |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| SHR2554 | Drug | SHR2554 is a selective small molecule inhibitor of the histone-lysine methyltransferase EZH2. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Incidence and severity of treatment-emergent adverse events (AEs) [Safety and Tolerability])(Part I) | The incidence and severity of treatment-emergent AEs will be collected and the safety and tolerability of SHR2554 will be assessed. | through study completion, an average of about 6 months |
| Recommended phase 2 dose (RP2D)(Part I) | Recommended phase 2 dose (RP2D) and/or maximum tolerated dose (MTD) will be established according to the incidence of dose-limiting toxicities (DLTs) of escalated doses of SHR2554. | 30 days since the date of first dose |
| Objective response rate (ORR)(Part II) | assessed by independent radiology review committee (IRC) | 60 days since the date of first dose |
| Measure | Description | Time Frame |
|---|---|---|
| Time to peak (Tmax) | Pharmacokinetics profile of a single dose SHR2554 and its metabolite (plasma): Time to peak (Tmax) of plasma concentration | Day 1 and Day 2 of the single dose |
| Maximum plasma concentration (Cmax) |
| Measure | Description | Time Frame |
|---|---|---|
| Effect of escalated doses of SHR2554 on the histone H3 lysine 27 trimethylation (H3K27me3) level(Part I-exploratory endpoints) | Analyze the level of H3K27me3 in the peripheral blood mononuclear cells of the subjects before and after the treatment of escalated doses of SHR2554. | day 1 of the single dose to day 1 of continuous medication cycle 2 |
Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Beijing Cancer Hospital, Peking University | Beijing | Beijing Municipality | China |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 38190117 | Derived | Song Y, Jin Z, Li ZM, Liu Y, Li L, He C, Su H, Zhou H, Li K, Hao S, Zuo X, Wu J, Li D, Wu M, Sun X, Qi J, Cai Z, Li Z, Li Y, Huang Y, Shen J, Xiao Z, Zhu J. Enhancer of Zeste Homolog 2 Inhibitor SHR2554 in Relapsed or Refractory Peripheral T-cell Lymphoma: Data from the First-in-Human Phase I Study. Clin Cancer Res. 2024 Apr 1;30(7):1248-1255. doi: 10.1158/1078-0432.CCR-23-2582. | |
| 35772429 |
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| ID | Term |
|---|---|
| D012008 | Recurrence |
| ID | Term |
|---|---|
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
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Pharmacokinetics profile of a single dose SHR2554 and its metabolite (plasma): Maximum plasma concentration (Cmax)
| Day 1 and Day 2 of the single dose |
| Halflife (T1/2) | Pharmacokinetics profile of a single dose SHR2554 and its metabolite (plasma): Halflife (T1/2) | Day 1 and Day 2 of the single dose |
| Clearance/ bioavailability (CL/F) | Pharmacokinetics profile of a single dose SHR2554 and its metabolite (plasma): Clearance/ bioavailability (CL/F) | Day 1 and Day 2 of the single dose |
| apparent volume of distribution/bioavailability (Vd/F) | Pharmacokinetics profile of a single dose SHR2554 and its metabolite (plasma): apparent volume of distribution/bioavailability (Vd/F) | Day 1 and Day 2 of the single dose |
| Area under curve (AUC) | Pharmacokinetics profile of a single dose SHR2554 and its metabolite (plasma): Area under curve (AUC) | Day 1 and Day 2 of the single dose |
| Area under curve, steady state (AUCss) | Pharmacokinetics profile of continuous medication of SHR2554 and its metabolite (plasma): Area under curve, steady state (AUCss) | Day 1 of cycle 1 to day 1 of cycle 4 (28 days/cycle) |
| Maximum plasma concentration, steady state (Cmax,ss) | Pharmacokinetics profile of continuous medication of SHR2554 and its metabolite (plasma): Maximum plasma concentration, steady state (Cmax,ss) | Day 1 of cycle 1 to day 1 of cycle 4 (28 days/cycle) |
| Time to peak, steady state (Tmax,ss) | Pharmacokinetics profile of continuous medication of SHR2554 and its metabolite (plasma): Time to peak, steady state (Tmax,ss) | Day 1 of cycle 1 to day 1 of cycle 4 (28 days/cycle) |
| Halflife (T1/2) | Pharmacokinetics profile of continuous medication of SHR2554 and its metabolite (plasma): Halflife (T1/2) | Day 1 of cycle 1 to day 1 of cycle 4 (28 days/cycle) |
| Apparent volume of distribution, steady state/bioavailability (Vss/F) | Pharmacokinetics profile of continuous medication of SHR2554 and its metabolite (plasma): Apparent volume of distribution, steady state/bioavailability (Vss/F) | Day 1 of cycle 1 to day 1 of cycle 4 (28 days/cycle) |
| Clearance/ bioavailability (CL/F) | Pharmacokinetics profile of continuous medication of SHR2554 and its metabolite (plasma): Clearance/ bioavailability (CL/F) | Day 1 of cycle 1 to day 1 of cycle 4 (28 days/cycle) |
| Accumulation index (Rac) | Pharmacokinetics profile of continuous medication of SHR2554 and its metabolite (plasma): Accumulation index (Rac) | Day 1 of cycle 1 to day 1 of cycle 4 (28 days/cycle) |
| Objective response rate (ORR) | Assess the response rate of subjects to the treatment of SHR2554 | every 8 weeks through study completion, an average of about 6 months |
| Progression-free survival (PFS) | Assess the survival condition of the subjects after the treatment of SHR2554 | every 8 weeks through study completion, an average of about 6 months |
| Duration of Response (DoR) | Assess the duration of complete/partial response after the treatment of SHR2554 | every 8 weeks through study completion, an average of about 6 months |
| Time to response(TTR)(Part II only) | Assess the time to initial response of subjects to the treatment of SHR2554 | 60 days since the date of first dose |
| OS(overall survival)(Part II only) | Assess the overall survival of subjects treated by SHR2554 | 2 years since the date of first dose |
| EZH2 gene mutation(Part I-exploratory endpoints) |
Assess the known mutation of EZH2 gene in tumor cells or tissues, analyze the relationship between efficacy and EZH2 mutation |
| within 2 weeks after the last dose |
| EZH2 expression level(Part I-exploratory endpoints) | Assess EZH2 expression level in tumor tissues, analyze the relationship between efficacy and EZH2 expression level | within 2 weeks after the last dose |
| Derived |
| Song Y, Liu Y, Li ZM, Li L, Su H, Jin Z, Zuo X, Wu J, Zhou H, Li K, He C, Zhou J, Qi J, Hao S, Cai Z, Li Y, Wang W, Zhang X, Zou J, Zhu J. SHR2554, an EZH2 inhibitor, in relapsed or refractory mature lymphoid neoplasms: a first-in-human, dose-escalation, dose-expansion, and clinical expansion phase 1 trial. Lancet Haematol. 2022 Jul;9(7):e493-e503. doi: 10.1016/S2352-3026(22)00134-X. |