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Relapsed or Refractory Mature Lymphoid NeoplasmsPhase 1NCT03603951

A Phase 1 Study of SHR2554 in Subjects With Relapsed or Refractory Mature Lymphoid Neoplasms

A Phase 1 study testing SHR2554 in people with Relapsed or Refractory Mature Lymphoid Neoplasms, run by Jiangsu HengRui Medicine Co., Ltd. at 1 site in China.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

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… Read more about this study

Who is it for?
Ages 18 to 70 years
What is being tested?
SHR2554
Could I receive a placebo?
No, everyone receives an active treatment
How many people
272 participants
Where
1 siteChina
Study dates
14 Aug 2018to 14 Aug 2026
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 70 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 18 to 70 years old (Adult, Senior)
  • Part I: Histologically or cytologically confirmed Mature lymphoid neoplasms; Part II: peripheral T cell lymphomas
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1；
  • Has a life expectancy of ≥12 weeks；
  • Resistant to standard therapy or no standard therapy available，have indications for treatment；
  • Have measurable disease （lymphoma participants，any nodes/nodal masses>1.5 cm in longest diameter (LDi) or extralymphatic sites of disease >1.0 cm in LDi；Multiple myeloma (MM) or Waldenström macroglobulinemia (WM) participants，serum M protein ≥0.5 g/dL or Bence Jones protein≥0.2 g/24 h）. （dose expansion study must satisfy）
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  • Has sufficient tumor tissue (slides or blocks) available for testing EZH2 mutation status and expression level. （dose expansion study must satisfy）
  • Diffuse large B-cell lymphoma (DLBCL) participants have immunohistochemistry test results of cell origin (germinal center B-cell-like (GCB) or non-GCB), as well as myelocytomatosis oncogene (MYC), B cell lymphoma/leukemia 2 (BCL2) and B-cell lymphoma 6 (BCL6), or provide sufficient tumor tissue for testing. （dose expansion study must satisfy）
  • With adequate bone marrow function;
  • With adequate renal and liver function;
  • Coagulation function index：PT ≤1.5×ULN，APTT ≤1.5×ULN；
  • Women of childbearing potential (WOCBP) should be proven to be negative by human chorionic gonadotropin (hCG) test in 7 days before the first dose of SHR2554. They must be willing and able to employ a highly effective method of birth control/contraception to prevent pregnancy from the day they sign the informed consent form (ICF) to at least 30 days after receiving the last dose of study treatment. Male subjects with WOCBP partner should receive Surgical sterilization or consent to employ a highly effective method of birth control/contraception to prevent pregnancy；
  • Any prior treatment-related clinically significant toxicities have resolved to ≤ Grade 1 per CTCAE version 4.03 or prior treatment-related toxicities evaluated by physicians are not clinically significant at time of enrollment.
  • Participant who has provided written consent to participate in the study and ability to comply with all aspects of the protocol.

Who cannot join

  • Prior exposure to other inhibitor(s) of EZH2.
  • FL 3b or (potentially) transformed FL
  • Participants with a presence of central nerves invasion
  • Auto-transplantation within 60 days or allo-transplantation within 90 days before the first dose of study drug； >1 grade graft-versus-host disease (GVHD) or using GVHD control medicines that are not allowed by this trial；
  • Major surgery or serious trauma within 4 weeks before the first dose of study drug.；
  • anti-tumor agents within 4 weeks before the first dose of study drug（such as chemotherapy, radiotherapy, immunotherapy, target therapy and other clinical research）；Use of Chinese Herbal within 2 weeks before the first dose of study drug；use of Glucocorticoids to anti tumor within 7 days before the first dose of study drug（equivalent to prednisone>20 mg/d）；
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  • Has known active infection with hepatitis B virus or hepatitis C virus（HBV DNA≥2×10^3 IU/mL，HCV RNA≥10^3 IU/mL）and liver dysfunction，need the intervention of anti-virus therapy;
  • Immunocompromised (i.e. has congenital immunodeficiency), including subjects known history of infection with human immunodeficiency virus (HIV) or has known active infection with tubercle bacillus；
  • Has an active infection or has a temperature > 38.5°C with unknown reasons（Investigators will decide the enrollment of participants with a fever that contributed to tumors）；
  • Has cardiovascular impairment，including history of congestive heart failure greater than New York Heart Association (NYHA) Class II, unstable angina, myocardial infarction, or stroke within 1 year prior to the planned first dose of study drug; or ventricular cardiac arrhythmia requiring medical treatment；
  • abnormal of ECG with clinical significance：such as prolongation of corrected QT interval using Fridericia's formula (QTcF)(male > 450 ms、female> 470 ms）；
  • History of cerebrovascular accident or transient ischemic attack within 6 months；
  • Has a prior malignancy other than the malignancies under study within 2 years- EXCEPTION: A subject with a history of a completely resected skin basal cell carcinoma, skin squamous-celled carcinoma, in situ cervical cancer or other in situ carcinomas, and has been relapse-free for 5 years；
  • Has serious acute/chronic disease or psychic disease，such as suicide intention or action in resent 1 year; or there are abnormal conditions that will increase the risk of using or managing study drug or affect the assessment of study results or investigator's judgment；
  • Staffs of institute sites directly related to the study or their family members, subordinates. Staffs of the sponsor pharmaceuticals company that directly related to the study；
  • Females who are pregnant or breastfeeding.
  • Inability to take oral medication, or any uncontrolled gastrointestinal condition (e.g., active gastroenteritis, chronic diarrhea, known diverticulosis, history of gastrectomy or gastric banding) that might impair the bioavailability of study drug. gastroesophageal reflux disease treated with proton pump inhibitors is eligible（should be no drug interaction）;
  • Use of known median or potent CYP3A4 or CYP3A5 inducers/inhibitors or P-gp inhibitors.
  • Any other major illness that, in the investigator's judgment, will substantially increase the risk associated with the subject's participation in this study.

Trial locations and contacts

1 site in 1 country.

China1 site

  • Beijing Cancer Hospital, Peking University

    Beijing, Beijing Municipality

Other trials in China

About this study

Official title: A Phase 1 Study to Characterize Safety, Tolerance, Pharmacokinetics and Efficacy of SHR2554 in Subjects With Relapsed or Refractory Mature Lymphoid Neoplasms

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.

Being tested
SHR2554
Keywords
SHR2554, EZH2 inhibitor, phase 1, mature lymphoid neoplasm
Medical subject headings
Recurrence

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • SHR2554Drug

    Also called EZH2 Inhibitor

    SHR2554 is a selective small molecule inhibitor of the histone-lysine methyltransferase EZH2.

Study groups in NCT03603951
Study groupRoleWhat they receive
SHR2554 treated groupExperimentalPart I：treated with escalated doses of EZH2 inhibitor SHR2554 respectively； Part II：treated with fixed dose (RP2D) SHR2554 respectively
Receives: Drug: SHR2554

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: through study completion, an average of about 6 months

  2. 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.

    Measured: 30 days since the date of first dose

  3. Objective response rate (ORR)（Part II）

    assessed by independent radiology review committee (IRC)

    Measured: 60 days since the date of first dose

Secondary outcomes (18)

  1. Time to peak (Tmax)

    Pharmacokinetics profile of a single dose SHR2554 and its metabolite (plasma): Time to peak (Tmax) of plasma concentration

    Measured: Day 1 and Day 2 of the single dose

  2. Maximum plasma concentration (Cmax)

    Pharmacokinetics profile of a single dose SHR2554 and its metabolite (plasma): Maximum plasma concentration (Cmax)

    Measured: Day 1 and Day 2 of the single dose

  3. Halflife (T1/2)

    Pharmacokinetics profile of a single dose SHR2554 and its metabolite (plasma): Halflife (T1/2)

    Measured: Day 1 and Day 2 of the single dose

  4. Clearance/ bioavailability (CL/F)

    Pharmacokinetics profile of a single dose SHR2554 and its metabolite (plasma): Clearance/ bioavailability (CL/F)

    Measured: Day 1 and Day 2 of the single dose

  5. 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)

    Measured: Day 1 and Day 2 of the single dose

  6. Area under curve (AUC)

    Pharmacokinetics profile of a single dose SHR2554 and its metabolite (plasma): Area under curve (AUC)

    Measured: Day 1 and Day 2 of the single dose

  7. Area under curve, steady state (AUCss)

    Pharmacokinetics profile of continuous medication of SHR2554 and its metabolite (plasma): Area under curve, steady state (AUCss)

    Measured: Day 1 of cycle 1 to day 1 of cycle 4 (28 days/cycle)

  8. 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)

    Measured: Day 1 of cycle 1 to day 1 of cycle 4 (28 days/cycle)

  9. 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)

    Measured: Day 1 of cycle 1 to day 1 of cycle 4 (28 days/cycle)

  10. Halflife (T1/2)

    Pharmacokinetics profile of continuous medication of SHR2554 and its metabolite (plasma): Halflife (T1/2)

    Measured: Day 1 of cycle 1 to day 1 of cycle 4 (28 days/cycle)

  11. 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)

    Measured: Day 1 of cycle 1 to day 1 of cycle 4 (28 days/cycle)

  12. Clearance/ bioavailability (CL/F)

    Pharmacokinetics profile of continuous medication of SHR2554 and its metabolite (plasma): Clearance/ bioavailability (CL/F)

    Measured: Day 1 of cycle 1 to day 1 of cycle 4 (28 days/cycle)

  13. Accumulation index (Rac)

    Pharmacokinetics profile of continuous medication of SHR2554 and its metabolite (plasma): Accumulation index (Rac)

    Measured: Day 1 of cycle 1 to day 1 of cycle 4 (28 days/cycle)

  14. Objective response rate (ORR)

    Assess the response rate of subjects to the treatment of SHR2554

    Measured: every 8 weeks through study completion, an average of about 6 months

  15. Progression-free survival (PFS)

    Assess the survival condition of the subjects after the treatment of SHR2554

    Measured: every 8 weeks through study completion, an average of about 6 months

  16. Duration of Response (DoR)

    Assess the duration of complete/partial response after the treatment of SHR2554

    Measured: every 8 weeks through study completion, an average of about 6 months

  17. Time to response（TTR）（Part II only）

    Assess the time to initial response of subjects to the treatment of SHR2554

    Measured: 60 days since the date of first dose

  18. OS（overall survival）（Part II only）

    Assess the overall survival of subjects treated by SHR2554

    Measured: 2 years since the date of first dose

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted27 Jul 2018
  2. Study start14 Aug 2018
  3. Primary completion14 Feb 2026 (estimated)
  4. Study completion14 Aug 2026 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
272 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03603951
Sponsor's protocol ID
SHR2554-I-101
Status last verified
Sep 2024
First submitted
10 Jul 2018
Last updated
1 Oct 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Undecided

Publications

  • 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.

    PubMed 38190117

  • 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.

    PubMed 35772429

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing SHR2554 in people with Relapsed or Refractory Mature Lymphoid Neoplasms, run by Jiangsu HengRui Medicine Co., Ltd. at 1 site in China.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 14 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 1 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Incidence and severity of treatment-emergent adverse events (AEs) [Safety and Tolerability])（Part I） (time frame: through study completion, an average of about 6 months). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03603951, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Oct 2024.

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