Clinical Trials /

Study of HBI-8000 With Nivolumab in Melanoma, Renal Cell Carcinoma and Non-Small Cell Lung Cancer

NCT02718066

Description:

A Phase 1b/2 Study to Assess the Safety and Efficacy of HBI-8000 in Combination with Nivolumab in Patients with Advanced Solid Tumors Including Melanoma, Renal Cell Carcinoma (RCC), and Non-Small Cell Lung Cancer (NSCLC). The primary objective of this study is: -To evaluate the safety and tolerability of HBI-8000 when combined with a standard dose and regimen of nivolumab, and to evaluate frequency and severity of toxicities of this combination treatment The secondary objectives of this study include: - To explore the efficacy of study treatment as measured by Objective Response Rate (ORR), Disease Control Rate (DCR), Clinical Benefit Rate (CBR), Duration of Response (DoR), Progression-Free Survival (PFS) in all subjects treated at RP2D - To obtain pharmacokinetics of twice weekly HBI-8000 when administered in combination with nivolumab administered once every two weeks (Phase 1b all sites) - To obtain pharmacokinetics of twice weekly HBI-8000 when administered in combination with nivolumab administered per package insert dose and administration (Phase 2 selected sites) - To characterize the effect of HBI-8000 on the electrocardiogram QT corrected (QTc) interval (Phase 1b only) Exploratory: - To investigate the kinetics and extent of histone acetylation in peripheral blood mononuclear cells (PBMC) at the RP2D of HBI-8000 (Phase 2 only) - To explore potential biomarkers for disease response through sequential sampling of blood and/or tumor tissue in subjects consenting to correlative sub-studies at participating sites (Phase 2 only) Dose Escalation (Phase 1b) will include up to 18 subjects, followed by Cohort Expansion (Phase 2) including up to 100 subjects (melanoma up to 60 subjects and NSCLC up to 40 subjects at MTD and/or RP2D.

Related Conditions:
  • Melanoma
  • Renal Cell Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Study of HBI-8000 With Nivolumab in Melanoma, Renal Cell Carcinoma and Non-Small Cell Lung Cancer
  • Official Title: A Phase 1b/2 Study to Assess the Safety and Efficacy of HBI-8000 in Combination With Nivolumab in Subjects With Advanced Solid Tumors Including Melanoma, Renal Cell Carcinoma (RCC), and Non-Small Cell Lung Cancer (NSCLC)

Clinical Trial IDs

  • ORG STUDY ID: HBI-8000-302
  • NCT ID: NCT02718066

Conditions

  • Melanoma
  • Renal Cell Carcinoma
  • Non-Small Cell Lung Cancer

Interventions

DrugSynonymsArms
HBI-8000 in combination with nivolumabFor HBI-8000: Chidamide, CS055; for nivolumab: OPDIVOHBI-8000 in combination with nivolumab

Purpose

A Phase 1b/2 Study to Assess the Safety and Efficacy of HBI-8000 in Combination with Nivolumab in Patients with Advanced Solid Tumors Including Melanoma, Renal Cell Carcinoma (RCC), and Non-Small Cell Lung Cancer (NSCLC). The primary objective of this study is: -To evaluate the safety and tolerability of HBI-8000 when combined with a standard dose and regimen of nivolumab, to determine Maximum Tolerated Dose (MTD) and/or Recommended Phase 2 Dose (RP2D) and to evaluate frequency and severity of toxicities of this combination treatment The secondary objectives of this study include: - To explore the efficacy of study treatment as measured by Objective Response Rate (ORR), Disease Control Rate (DCR), Clinical Benefit Rate (CBR), Duration of Response (DoR), Progression-Free Survival (PFS) in all subjects treated at RP2D - To obtain pharmacokinetics of twice weekly HBI-8000 when administered in combination with nivolumab administered once every two weeks (Phase 1b all sites; Phase 2 selected sites) - To characterize the effect of HBI-8000 on the electrocardiogram QT corrected (QTc) interval (Phase 1b only) Exploratory: -To investigate the kinetics and extent of histone acetylation in peripheral blood mononuclear cells (PBMC) at the RP2D of HBI-8000 (Phase 2 only) Dose Escalation (Phase 1b) will include up to 18 subjects, followed by Cohort Expansion (Phase 2) including up to 20 subjects per tumor indication at MTD and/or RP2D (including those treated in Phase 1b).

Detailed Description

      A Phase 1b/2 Study to Assess the Safety and Efficacy of HBI-8000 in Combination with
      Nivolumab in Patients with Advanced Solid Tumors Including Melanoma, Renal Cell Carcinoma
      (RCC), and Non-Small Cell Lung Cancer (NSCLC).

      The primary objective of this study is:

      -To evaluate the safety and tolerability of HBI-8000 when combined with a standard dose and
      regimen of nivolumab, to determine Maximum Tolerated Dose (MTD) and/or Recommended Phase 2
      Dose (RP2D) and to evaluate frequency and severity of toxicities of this combination
      treatment

      The secondary objectives of this study include:

        -  To explore the efficacy of study treatment as measured by Objective Response Rate (ORR),
           Disease Control Rate (DCR), Clinical Benefit Rate (CBR), Duration of Response (DoR),
           Progression-Free Survival (PFS) in all subjects treated at RP2D

        -  To obtain pharmacokinetics of twice weekly HBI-8000 when administered in combination
           with nivolumab administered once every two weeks (Phase 1b all sites; Phase 2 selected
           sites)

        -  To characterize the effect of HBI-8000 on the electrocardiogram QT corrected (QTc)
           interval (Phase 1b only)

      Exploratory:

      -To investigate the kinetics and extent of histone acetylation in peripheral blood
      mononuclear cells (PBMC) at the RP2D of HBI-8000 (Phase 2 only)

      Dose Escalation (Phase 1b) will include up to 18 subjects, followed by Cohort Expansion
      (Phase 2) including up to 20 subjects per tumor indication at MTD and/or RP2D (including
      those treated in Phase 1b).

      HBI-8000 tablets will be administered at 20, 30, 40 mg/dose, orally twice a week until MTD or
      40 mg in Phase 2, if MTD is not reached.

      Nivolumab: 240 mg intravenous infusions every 2 weeks. A treatment cycle consists of 28 days.
      Treatment continues until disease progression or unacceptable toxicity.
    

Trial Arms

NameTypeDescriptionInterventions
HBI-8000 in combination with nivolumabExperimentalHBI-8000 dose escalation 20mg, 30mg, 40mg, orally, twice weekly; in combination with Nivolumab 240mg intravenous infusions every 2 weeks.
  • HBI-8000 in combination with nivolumab

Eligibility Criteria

        Inclusion criteria. Patients may be entered in the study only if they meet all of the
        following criteria:

        1. Adults at least 18 years of age. 2. Eastern Cooperative Oncology Group (ECOG)
        performance status ≤1. 3.

          1. Subjects with histopathologically or cytologically confirmed diagnosis of cutaneous
             Melanoma, RCC or NSCLC, for whom the use of nivolumab is indicated. NSCLC subjects
             with EGFR or ALK genomic aberrations in tumor should have disease progression on
             FDA-approved therapy for these aberrations prior to receiving nivolumab (Phase 1b).

          2. Subjects with histopathologically or cytologically confirmed diagnosis of cutaneous
             Melanoma, or NSCLC, for whom the use of nivolumab is indicated. NCSLC subjects with
             EGFR or ALK genomic aberrations in tumor should have disease progression on
             FDA-approved therapy for these aberrations prior to receiving nivolumab (Phase 2
             expansion).

          3. Cutaneous melanoma and NSCLC patients whose disease has progressed after achieving PR
             or CR on previous treatment with antagonists to PD1-PD-L1 axis, or patients whose
             disease remains stable on previous treatment with antagonists to PD1-PD-L1 axis and
             modification to treatment is being considered. NSCLC patients with EGFR or ALK genomic
             aberrations in tumor should have disease progression on FDA-approved therapy for these
             aberrations prior to receiving nivolumab (Phase 2 expansion).

             4. Subject must have at least one measurable target lesion as defined by Response
             Evaluation Criteria in Solid Tumors (RECIST) v.1.1.

             5. All prior systemic therapy (chemotherapy, mutation targeting therapy, immune
             checkpoint therapy), surgical or radiation treatment must have been completed at least
             4 weeks before study drug administration (2 weeks for palliative radiotherapy, 1 week
             for minor surgery) pending full recovery from therapy.

             6. The following laboratory results within 7 days prior to study drug administration:
             Adequate hematopoietic, electrolyte, hepatic, and renal laboratory findings as defined
             below: WBC ≥3000/μL, Neutrophils ≥1500/μL, Platelets ≥100x103/μL, Hemoglobin ≥9.0g/dL
             independent of transfusion, Creatinine ≤1.5mg/dL, AST and ALT ≤3x ULN, Alkaline
             phosphatase ≤2.5x ULN unless bone metastases present, Bilirubin ≤1.5x ULN (unless
             known Gilbert's disease where it must be ≤3x ULN) and serum albumin ≥3.0g/dL.

             7. Life expectancy ≥12 weeks. 8. A negative serum pregnancy test at baseline for women
             of childbearing potential.

             9. Are willing to abstain from heterosexual activity or practice physical barrier
             contraception prior to time of study entry to at least 5 months after the last day of
             treatment.

             10. Have the ability to understand and the willingness to sign a written informed
             consent document.

             Exclusion criteria. Subjects who fulfill any of the following criteria at screening
             will not be eligible for admission into the study:

               1. History of Grade 3 or above hypersensitivity reactions to other monoclonal
                  antibodies.

               2. Subjects with a history of a cardiovascular illness including: QTcF >450ms in
                  male, and >470ms in female, congenital long QT syndrome, congestive heart failure
                  (New York Heart Association Grade III or IV); unstable angina or myocardial
                  infarction within the previous 6 months; or symptomatic cardiac arrhythmia
                  despite medical management.

               3. Uncontrolled hypertension, SBP >160 or DBP >100.

               4. Subjects with untreated, or treated brain metastasis, unless stable for 4 weeks
                  or more and not requiring steroids.

               5. Presence of leptomeningeal disease.

               6. History of hemorrhagic diarrhea, inflammatory bowel disease, active uncontrolled
                  peptic ulcer disease or recurrent pleural effusion requiring repetitive
                  palliative thoracentesis within 3 months prior to study entry, except for
                  subjects with a pleurex port. and immune-mediated toxicity leading to treatment
                  discontinuation

               7. Active, known, or suspected autoimmune disease, except for type I diabetes
                  mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such
                  as vitiligo, psoriasis, or alopecia).

               8. Active uncontrolled bacterial, viral, or fungal infection requiring systemic
                  therapy.

               9. Known history of testing positive for human immunodeficiency virus (HIV), known
                  acquired immunodeficiency syndrome (AIDS).

              10. Active hepatitis B (serum hepatitis B surface antigen [HBV sAg] positive), or
                  hepatitis C (HCV antibody test or serum hepatitis C RNA positive) indicating
                  acute or chronic infection.

              11. Subjects with a condition requiring systemic treatment with either
                  corticosteroids (>10mg daily prednisone equivalents) or other immunosuppressive
                  medications within 14 days of study drug administration. Inhaled or topical
                  steroids are permitted.

              12. Use of other investigational agent (drug not marketed for any indication) within
                  28 days or at least 5 half-lives (whichever is longer) before study drug
                  administration.

              13. Pregnant or breast-feeding women.

              14. Second malignancy unless in remission for 2 years, except for non-melanomatous
                  skin cancer, carcinoma in situ of the cervix treated with curative intent.

              15. Underlying medical conditions that, in the Investigator's opinion, will make the
                  administration of study drug hazardous or obscure the interpretation of toxicity
                  determination or adverse events.

              16. Unwilling or unable to comply with procedures required in this protocol.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Determination of the Recommended for Phase 2 Dose (RP2D) (mg)
Time Frame:12 months
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Efficacy Outcome: Response Rate (%).
Time Frame:18 months
Safety Issue:
Description:

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:HUYA Bioscience International

Trial Keywords

  • HBI-8000
  • Nivolumab
  • Melanoma
  • Renal Cell Carcinoma
  • Non-Small Cell Lung Cancer

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