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A Phase I Study to Evaluate the Safety and Clinical Activity of HH2853.

NCT04390737

Description:

This is 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,in the 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.

Related Conditions:
  • Diffuse Large B-Cell Lymphoma
  • Follicular Lymphoma
  • Malignant Solid Tumor
Recruiting Status:

Not yet recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Phase I Study to Evaluate the Safety and Clinical Activity of HH2853.
  • 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

Clinical Trial IDs

  • ORG STUDY ID: HH2853-G101
  • NCT ID: NCT04390737

Conditions

  • Non Hodgkin Lymphoma
  • Advanced Solid Tumor

Interventions

DrugSynonymsArms
HH2853Dose escalation study of HH2853

Purpose

This is 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,in the 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.

Detailed Description

      HH2853 is developed by Shanghai Haihe Pharmaceutical Co., Ltd.and it is a selective EZH1/2
      dual inhibitor. HH2853 could potently inhibits both wild type and mutant EZH2
      methyltransferase activity .This is 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,in the 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.
    

Trial Arms

NameTypeDescriptionInterventions
Dose escalation study of HH2853ExperimentalTo determine MTD and/or RP2D and to evaluate the safety, tolerability of HH2853
  • HH2853

Eligibility Criteria

        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 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 109/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 109/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, 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 ≥ 103 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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Max Tolerance Does(MTD)/Recommended Phase Two Dose(RP2D)
Time Frame:28 days
Safety Issue:
Description:To determine MTD and/or RP2D and to evaluate the safety, tolerability of HH2853 administered orally on a continuous twice daily (BID) schedule in patients with relapsed/refractory Non-Hodgkin's lymphomas or advanced solid tumors

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:ShangHai HaiHe Pharmaceutical

Trial Keywords

  • Non Hodgkin Lymphoma
  • advanced solid tumor
  • PRC2
  • EZH 1
  • EZH 2

Last Updated

May 14, 2020