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Evaluate the Safety and Clinical Activity of HH2853

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT04390737
Recruitment Status : Recruiting
First Posted : May 15, 2020
Last Update Posted : March 9, 2021
Information provided by (Responsible Party):
Haihe Biopharma Co., Ltd.

Brief Summary:
This is an open-label, multicenter, first-in-human phase I dose escalation study. HH2853 will be administered orally on a continuous BID schedule on a continuous 28-day treatment cycle. 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.

Condition or disease Intervention/treatment Phase
Non-Hodgkin's Lymphoma, Relapsed Non-Hodgkin's Lymphoma Refractory Advanced Solid Tumor Drug: HH2853 Tablets Phase 1

Detailed Description:
This first-in-human study of HH2853 will be conducted in patients with non-Hodgkin's lymphomas or patients with advanced solid tumors that have relapsed or are refractory to prior therapies and have a high degree of unmet medical need in terms of available treatment options. The purpose of the study is to determine the safety, tolerability, pharmacokinetics (PK), pharmacodynamic (PD), the Maximum Tolerated Dose (MTD) and/or the Recommended Phase II dose (RP2D) and preliminary efficacy of HH2853 administered orally on a continuous twice daily (BID) schedule in adult patients with relapsed/refractory Non-Hodgkin's lymphomas or advanced solid tumors.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A First-in-Human, Open Label, Phase I Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Clinical Activity of HH2853, an EZH1/2 Inhibitor, in Patients With Relapsed/Refractory Non-Hodgkin's Lymphomas or Advanced Solid Tumors
Actual Study Start Date : September 8, 2020
Estimated Primary Completion Date : June 30, 2022
Estimated Study Completion Date : June 30, 2023

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: HH2853 administered on a BID schedule in continuous 28-day treatment cycles
HH2853 is supplied as tables with dosage strength of 25mg and 200mg. HH2853 is administered orally on a continuous BID schedule in 28-day treatment cycles. Patients in accelerated titration part (ATD) should be administered a single dose on the first day in order to evaluate the PK of a single dose administration. Dosing is twice daily from the second day thereafter.
Drug: HH2853 Tablets
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 Outcome Measures :
  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

Secondary Outcome Measures :
  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

Other Outcome Measures:
  1. Objective response rate (ORR) [ Time Frame: 28-day treatment cycles ]
    Assess the preliminary efficacy of HH2853

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

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

    1. Relapsed/refractory histologically documented non-Hodgkin's lymphoma (NHL) must have received at least 2 prior systemic therapies and should meet the following criteria:

      • Follicular lymphoma (FL) must meet criteria requiring systemic treatment per the GELF criteria and there is no standard salvage regimen available;
      • Diffuse large B-cell lymphoma NOS (2016 WHO classification of lymphoma neoplasms) relapsed or refractory with at least 2 prior regimen (e.g., rituximab, cyclophosphamide, doxorubicin, vincristine, prednisolone [R-CHOP]) and not a candidate for standard salvage regimens or autologous or allogeneic stem cell transplant.

      Patients without treatment options available known to provide clinical benefit are also eligible.

    2. Solid tumors that meet the following criteria: histologically or cytologically documented advanced recurrent or metastatic solid tumor. Measurable or evaluable disease by RECIST v1.1 in at least 1 site; disease progression with the last line of therapy and at least one prior standard of care regimens, or tumor for which there is no approved therapy, or for which standard therapy is unsuitable or refused. Patients must have disease not amenable to surgery, radiation, or combined modality therapy with curative intent. Patients without treatment options available known to provide clinical benefit are also eligible.
  4. Eastern Cooperative Oncology Group (ECOG) performance status ≤1;
  5. Predicted life expectancy of ≥ 3 months;
  6. 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

      *For calculated creatinine clearance (Ccr) value, the eligibility should be determined using the Cockcroft-Gault formula:

      1. Male Ccr (mL/mim) = body weight (kg) x (140-age)/[72 x creatinine (mg/dL)]
      2. Female Ccr (mL/min) = male Ccr x 0.85 ** A measured value Ccr value (i.e. not calculated) should meet this criterion.
    4. Platelets ≥ 100 x 10^9/L (no Platelet transfusion for 7 days prior to screening)
    5. Hemoglobin (Hgb) ≥ 9 g/dL (no RBC transfusion for 7 days prior to screening)
    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)

Exclusion Criteria:

  1. Any cancer-directed therapy (chemotherapy, antibody therapy, radiotherapy, hormonal therapy, biologic or immunotherapy, Chinese medicine/Chinese patent medicine with anti-tumor effect, etc.) within 28 days;
  2. Symptomatic CNS metastases that are neurologically unstable or requiring increasing doses of steroids to control CNS disease. Note: Any major surgery, radiotherapy or immunotherapy within the 4 weeks prior to first dose of study drug, or palliative radiotherapy to a single symptomatic lesion within the 2 weeks prior to first dose of study drugs;
  3. Patients with prior transplant are excluded; however, patients who have previously received an autologous stem cell transplant are allowed if a minimum of 100 days has elapsed from the time of transplant and the patient has recovered from transplant-associated toxicities prior to the first dose of HH2853. Patients who have previously received an allogeneic stem cell transplant are also allowed if a minimum of 6 months has elapsed prior to the first dose of HH2853;
  4. Major surgery within 4 weeks prior to first dose;
  5. Current use of a prohibited medication or expected to require any of these medications during treatment with study drug (see Section 6.4);
  6. 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). However, patients that can be controlled with treatment are eligible;
  7. Concomitant malignancies or previous malignancies with less than 2 years of disease-free interval at the time of enrollment (but basal cell carcinoma skin cancer, cervical CIS (carcinoma in situ), CIS of the breast, localized or low Gleason grade prostate cancer, and < T2 bladder cancer can be included);
  8. 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 (see Section 6.4).
  9. Any toxicities from prior treatment that have not recovered to ≤ CTCAE Grade 1 before the start of study drug, with exception of hair loss or fatigue;

    a) Lymphoma patients with ≤ Grade 3 lymphopenia can be enrolled at the discretion of the investigator

  10. Packed red blood cell or platelet transfusion within 7 days of screening laboratory tests;
  11. Gastrointestinal condition which could impair absorption of study medication;
  12. Psychological, familial, sociological or geographical conditions that do not permit compliance with the protocol;
  13. 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. QTc F interval >470 msec
    3. History or current evidence of serious uncontrolled ventricular arrhythmias
    4. Myocardial infarction, severe/unstable angina, symptomatic congestive heart failure (Class III or IV heart failure as defined by the New York Heart Association (NYHA) functional classification system, see Appendix 14.5) within the previous 3 months; if > 3 months, cardiac function must be within normal limits and the patient must be free of cardiac-related symptoms.
  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 (See Appendix 14.4):

Patients who do not meet the following requirements will be excluded:

  • For women: negative pregnancy test for females of child-bearing potential; must be surgically sterile, postmenopausal (defined as no menstrual cycle for at least 12 consecutive months), or compliant with an acceptable contraceptive regimen (2 highly effective forms, such as oral contraceptives, condom with spermicide, etc.) during and for 3 months after the treatment period. Abstinence is not considered as an adequate contraceptive regimen;
  • For men: must be surgically sterile, or compliant with a contraceptive regimen (as above) during and for a minimum of 3 months after the treatment period.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT04390737

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Contact: Yanli Xu +86 21 20568888
Contact: Jia Wang +86 21 20568888

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United States, Arizona
Mayo Clinic Recruiting
Phoenix, Arizona, United States, 85054
Contact: Javier Munoz    480-342-1840   
United States, Florida
Mayo Clinic Recruiting
Jacksonville, Florida, United States, 32224
Contact: Han Tun    904-953-2000   
United States, Minnesota
Mayo Clinic Recruiting
Rochester, Minnesota, United States, 55905
Contact: Patrick Johnston    507-284-6322   
United States, Texas
NEXT Oncology Recruiting
San Antonio, Texas, United States, 78240
Contact: Raghad Karim    210-580-9500   
China, Beijing
Beijing Cancer Hospital Recruiting
Beijing, Beijing, China, 100142
Contact: Lin Shen    86 13911219511   
Contact: Yuqin Song    86 13683398726   
Sponsors and Collaborators
Haihe Biopharma Co., Ltd.
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Responsible Party: Haihe Biopharma Co., Ltd. Identifier: NCT04390737    
Other Study ID Numbers: HH2853-G101
First Posted: May 15, 2020    Key Record Dates
Last Update Posted: March 9, 2021
Last Verified: February 2021

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Haihe Biopharma Co., Ltd.:
Phase I
EZH 1/2 inhibitor
Additional relevant MeSH terms:
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Lymphoma, Non-Hodgkin
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases