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NCT Number: NCT04390737

Evaluate the Safety and Clinical Activity of HH2853

This is an open-label, multicenter, first-in-human phase I/II study which is composed of 3 parts: phase I dose escalation, phase I dose extension and phase II. HH2853 will be administered orally on a continuous BID schedule on a continuous 28-day treatment cycle.

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Key information

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1 / Phase 2

Primary location

The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China

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About this study

Phase I:

Phase I dose escalation The accelerated titration (ATD) incorporated with Bayesian Optimal Interval design (BOIN) will be used to assess the DLT, safety, tolerability, MTD and furthermore, to establish the RP2D. DLT assessment is only applicable to phase I dose escalation.

Eligible patients will be enrolled in the ascending dose until MTD/RP2D is established.

Phase I dose extension During the dose escalation phase, a dose extension with additional patients will be included in order to further evaluate the tolerability, pharmacokinetics, and efficacy at doses that have been evaluated as safe. The number of patients to be enrolled in each dose extension cohort is up to 15, but the final number of dose level can be determined and the final patient number at each dose level can be adjusted slightly based on available safety, efficacy, PK, and PD data upon agreement from sponsor and investigators (e.g. safety evaluation meeting). For phase I dose extension, approximately 30 patients will be enrolled based on initial estimate, but the final total number of patients will depend on the number of dose levels extended and patient number at each dose level.

The total number of patients is estimated to be approximately 60 patients for phase I dose escalation and dose extension, but the final total number of patients will depend upon the number of dose cohorts to reach MTD/RP2D, and patient number at each dose level.

Phase II(China Only):

Phase II is planned after the completion of phase I. Up to approximately 193 patients will be enrolled as outlined below:

  • Cohort 1: Relapsed/Refractory FL (n≈56)
  • Cohort 2: Epithelioid sarcoma (n≈77)
  • Cohort 3: Relapsed/Refractory PTCL, other relapsed/refractory Non-Hodgkin's lymphomas with EZH2 mutation, or advanced solid tumors with specific genetic alterations, including EZH2 mutation, INI1 deficiency, BAP1 deficiency, ARID1A mutation, or/and SMARCA4 mutation (n≈60)

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Provided signed written informed consent prior to initiation of any study-related procedures;
  • Males and females ≥ 18years of age at the time of consent are obtained (or meet the country's regulatory defined adult legal age);
  • Tumor type criteria:

The specific requirements for specific subtypes of recurrent/refractory non Hodgkin's lymphoma (NHL) confirmed by histology are as follows:

Histologically confirmed follicular lymphoma (FL) that has been treated with at least two lines of systemic therapy (at least one regimen based on anti-CD20 monoclonal antibodies) according to GELF criteria or as determined by researchers (Grade 1-3a); Relapsed/refractory diffuse large B-cell lymphoma - non-specific (DLBCL NOS, 2016 World Health Organization Lymphoma Classification) that has received at least two treatment regimens in the past (at least one with CD20 monoclonal antibody as the main treatment, with a maximum number of treatment lines<5), and is not a candidate for salvage treatment or autologous/allogeneic stem cell transplantation.

Relapsed/refractory clinicopathologically documented PTCL with at least 1 line of prior systemic treatment (maximum <5 lines). Solid tumors that meet the following criteria:

  • Histologically or cytologically documented advanced recurrent or metastatic solid tumor.
  • Phase I dose escalation: Measurable or evaluable lesions by RECIST v1.1 in at least 1 site; phase I dose extension and phase II: Measurable target lesions by RECIST v1.1 in at least 1 site. (Lesions that have been treated with radiotherapy or other local treatment are generally considered unmeasurable unless there is definite progression of the lesion.)
  • Patients must have disease not amenable to surgery, radiation, or combined modality therapy with curative intent. One of the following criteria should be met.

Patients must experience at least one prior standard therapy. Disease progression occurred on or after last line of therapy, or intolerant to last line of therapy (maximum ≤3 lines, Patients without treatment options available known to provide clinical benefit are also eligible upon agreement from investigator and sponsor) There is no approved therapy, or for which standard therapy is unsuitable or refused by patients after being fully informed.

For epithelioid sarcoma in Phase I and Phase II cohort 2:

  • Confirmed by local histology or cytology
  • Patients with unresectable locally delayed or metastatic epithelioid sarcoma who have undergone treatment (including those who have failed treatment and developed intolerable toxicity).

For solid tumors in Phase I and Phase II queue 3:

  • Confirmed by local pathology as advanced recurrent or metastatic solid tumor.
  • Patients must have disease not amenable to surgery, radiation, or combined modality therapy with curative intent 4. Eastern Cooperative Oncology Group (ECOG) performance status ≤1; 5. Availability of archival tissue within three years 6. Relapsed/Refractory FL, Epithelioid sarcoma, relapsed/refractory PTCL, other relapsed/refractory non-Hodgkin's lymphomas with EZH2 mutation, and advanced solid tumors with specific genetic alterations, including EZH2 mutation, INI1 deficiency, BAP1 deficiency, ARID1A mutation, or/and SMARCA4 mutation 7. Predicted life expectancy of ≥ 3 months; 8. Patient must meet the following laboratory values: 1.Serum total Bilirubin ≤ 1.5 x ULN or ≤ 3.0 mg/dL for patients with Gilbert's syndrome 2.AST/SGOT and ALT/SGPT ≤ 2.5 x ULN or ≤ 5 x ULN if liver metastases are present 3.24-hour creatinine clearance (calculated* or measured value**)≥ 50 mL/min 4.Platelets ≥ 1 x LLN (no Platelet transfusion for 7 days prior to screening) 5.Hemoglobin (Hgb) ≥ 9 g/dL 6.Absolute Neutrophil Count (ANC) ≥ 1.0 x 10^9/L 7.Adequate coagulation function: International normalized ratio (INR) <1.3 (or <3.0 on anticoagulants) 9. Measurable lesion

Exclusion criteria

  • Any cancer-directed therapy within 28 days or five half-lives prior to first dose; Small molecule anticancer therapy within 2 weeks or five half-lives; Local radiotherapy within 14 days of first dose.
  • Symptomatic CNS metastases that are neurologically unstable or requiring increasing doses of steroids to control CNS disease.
  • Patients with prior transplant are excluded;
  • Major surgery within 4 weeks prior to first dose;
  • A prohibited medication or expected to require any of these medications during treatment with study drug within 2 weeks of first dose;
  • HIV (human immunodeficiency virus) infection, active hepatitis B or hepatitis C patients (HBsAg positive patients with HBV (hepatitis B virus) DNA ≥ 10^3 copies or ≥ 200 IU/mL; HCV antibody test results are positive, and HCV (hepatitis C virus) RNA PCR test results are positive).
  • Concomitant malignancies or previous malignancies
  • Concurrent use of therapeutic warfarin is allowed. However, anticoagulants that do not have reversal agents available are prohibited except low molecular weight heparin and direct oral anticoagulants.
  • Any toxicities from prior treatment that have not recovered to ≤ CTCAE Grade 1
  • There were ≥ 3 lesions with punctate bleeding, any active bleeding, intratumoral bleeding, known bleeding tendencies, or treatment with antiplatelet/antithrombotic drugs.
  • Gastrointestinal condition which could impair absorption of study medication;
  • Psychological, familial, sociological or geographical conditions that do not permit compliance with the protocol;
  • Cardiac exclusion criteria:

1.History of acute coronary syndromes (including myocardial infarction and unstable angina), coronary angioplasty, or stenting within the past 3 months prior to first dose of study drug; 2.Fridericia's corrected QT interval (QTcF) > 450 ms (for male) and > 470 ms (for female) on ECG conducted during screening; 3.Congenital long QT syndrome, or any known history of torsade de pointes (TdP), or family history of unexplained sudden death; 4.History or current evidence of serious uncontrolled ventricular arrhythmias; 5.Symptomatic congestive heart failure (Class III or IV heart failure as defined by the New York Heart Association (NYHA) functional classification system) within the previous 3 months; 6.Left ventricular ejection fraction (LVEF) < 50%; 14. Any evidence of serious active infections requiring antibiotics; 15. Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to the study drug or their excipients; 16. Pregnant or breast-feeding female; 17. Contraception: 18. Other serious illness or medical conditions at the Investigator's discretion, that may influence study results 19. Previously received treatment with EZH2 or EZH1/2 inhibitors. 20. Grade 3b FL or evidence of transformation to invasive lymphoma

Treatment and study plan

HH2853 Tablets

Drug

Proposed daily dose (BID): 50mg, 100mg, 200mg, 400mg, 600mg, 800mg, 1000mg. It is possible for additional and/or intermediate dose levels to be added during the course of the study. Cohorts may be added at any dose level below the MTD in order to better understand safety, PK or PD.

Primary outcomes

  1. Maximum tolerated Dose (MTD)

    Time frame: 28-day treatment cycles

    Determine MTD of HH2853

  2. Recommended phase II dose (RP2D)

    Time frame: 28-day treatment cycles

    Determine RP2D of HH2853

  3. Adverse events assessed according to NCI-CTCAE V5.0

    Time frame: 28-day treatment cycles

    Evaluate the safety of HH2853

  4. Dose limiting toxicities (DLT)

    Time frame: 28-day treatment cycles

    Evaluate the tolerability of HH2853

  5. Objective response rate (ORR)

    Time frame: 28-day treatment cycles

    Assess the preliminary efficacy of HH2853

Secondary outcomes

  1. AUClast

    Time frame: 28-day treatment cycles

    Characterize the pharmacokinetic profile of HH2853

  2. AUCinf

    Time frame: 28-day treatment cycles

    Characterize the pharmacokinetic profile of HH2853

  3. Cmax

    Time frame: 28-day treatment cycles

    Characterize the pharmacokinetic profile of HH2853

  4. Tmax

    Time frame: 28-day treatment cycles

    Characterize the pharmacokinetic profile of HH2853

  5. CL/F

    Time frame: 28-day treatment cycles

    Characterize the pharmacokinetic profile of HH2853

  6. Vz/F

    Time frame: 28-day treatment cycles

    Characterize the pharmacokinetic profile of HH2853

  7. Terminal half-life (T1/2)

    Time frame: 28-day treatment cycles

    Characterize the pharmacokinetic profile of HH2853

  8. Duration of response (DoR)

    Time frame: 28-day treatment cycles

    Assess the preliminary efficacy of HH2853

  9. Progression-free survival (PFS)

    Time frame: 28-day treatment cycles

    Assess the preliminary efficacy of HH2853

  10. Disease control rate (DCR)

    Time frame: 28-day treatment cycles

    Assess the preliminary efficacy of HH2853

  11. Time to response (TTR)

    Time frame: 28-day treatment cycles

    Assess the preliminary efficacy of HH2853

  12. Time to progression (TTP)

    Time frame: 28-day treatment cycles

    Assess the preliminary efficacy of HH2853

  13. Clinical Outcome

    Time frame: 28-day treatment cycles

    Explore the association between potential biomarker and the clinical outcome

Other outcomes

  1. Overall survival (ORR)

    Time frame: 28-day treatment cycles

    Assess the preliminary efficacy of HH2853

  2. Change in tri-methylation of Histone H3K27 (H3K27me3)

    Time frame: 14-day treatment

    Assss the pharmacodynamic response

  3. Biomarker Status

    Time frame: 28-day treatment cycles

    Explore the relationship between the alteration status of biomarker and treatment efficacy

  4. Overall survival (OS)

    Time frame: 28-day treatment cycles

    Assess the preliminary efficacy of HH2853

Study contacts

Contact information is provided by the study sponsor or research team.

Haiyue Chen

CONTACT

[email protected]

+86 21 20568888

Sponsors and collaborators

Lead sponsor

Haihe Biopharma Co., Ltd.

Industry

Registry information

Official study title

A Phase I/II Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Clinical Activity of HH2853 in Patients With Relapsed/Refractory Non-Hodgkin's Lymphomas or Advanced Solid Tumors

Important dates

Study start
2020
Primary completion
2027
Study completion
2028
First posted
May 15, 2020
Registry last updated
Jan 30, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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