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Clinical Trial 18874

Cancer Type:
Interventions:BMS-936558 (Nivolumab); HBI-8000 (chidamide); Nivolumab

Study Type: Treatment
Phase of Study: Phase I/II
Investigators:

  • Nikhil Khushalani

Call 813-745-6100
or 1-800-679-0775
Overview

Study Title

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)

Summary

This study is being done to learn more about the safety and activity of a new investigational drug, HBI-8000, when combined with an approved drug, nivolumab, for treating cancer. An investigational drug is a drug that has not been approved for marketing to the general public by the Food and Drug Administration (FDA) but is allowed to be tested in people for research purposes.

Objective

Primary: - 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. Secondary: - 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 patients treated at RP2D. - To obtain pharmacokinetics of twice weekly HBI-8000 when administered in combination with nivolumab administered once every two weeks. - To characterize the effect of HBI-8000 on the electrocardiogram QTc interval.

Inclusion Criteria

  • Adults at least 18 years of age.
  • Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1.
  • Potential participants histopathologically or cytologically confirmed diagnosis of non-uveal Melanoma, renal cell carcinoma (RCC) or non-small cell lung cancer (NSCLC), for whom the use of nivolumab is indicated. (Phase 2 expansion).
  • Non-uveal melanoma and NSCLC patients whose disease has progressed after achieving stable disease (SD) for at least 3 months, with partial response (PR) or complete response) CR as the best response that has been documented by imaging studies on previous treatment with a PD-(L)1 inhibitor with proven efficacy (Phase 2 expansion)
  • Must have at least one measurable target lesion as defined by Response Evaluation Criteria in Solid Tumors (RECIST) v.1.1. Subjects with melanoma must have tumor tissue available from a metastatic or unresectable site for PD-(L)1 and correlative biomarker analysis.
  • 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.
  • The following laboratory results within 7 days prior to study drug administration: Adequate hematopoietic, electrolyte, hepatic, and renal laboratory findings as defined below: white blood cells (WBC) ≥ 3000/μL, neutrophils ≥ 1500/μL, platelets ≥ 100x103/μL, hemoglobin ≥ 9.0 g/dL independent of transfusion, creatinine ≤ 1.5 mg/dL, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 x upper limit of normal (ULN), alkaline phosphatase ≤ 2.5 x ULN unless bone metastases present, bilirubin ≤ 1.5 x ULN (unless known Gilbert¿s disease where it must be ≤3xULN) and serum albumin ≥3.0 g/dL.
  • Life expectancy ≥ 12 weeks.
  • A negative serum pregnancy test at baseline for women of childbearing potential.
  • 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.
  • Have the ability to understand and the willingness to sign a written informed consent document.

  • Exclusion Criteria

  • History of Grade 3 or above hypersensitivity reactions to other monoclonal antibodies.
  • A history of a cardiovascular illness including: QTcF > 450 ms in male, and > 470 ms 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.
  • Uncontrolled hypertension, SBP> 160 or DBP>100.
  • Untreated, or treated brain metastasis, unless stable for 4 weeks or more and not requiring steroids.
  • Presence of leptomeningeal disease.
  • 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
  • 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).
  • Active uncontrolled bacterial, viral, or fungal infection requiring systemic therapy.
  • Known history of testing positive for human immunodeficiency virus (HIV), known acquired immunodeficiency syndrome (AIDS).
  • 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.
  • A condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids are permitted.
  • 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.
  • Pregnant or breast-feeding women.
  • Second malignancy unless in remission for 2 years, except for non-melanomatous skin cancer, carcinoma in situ of the cervix treated with curative intent.
  • 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.
  • Unwilling or unable to comply with procedures required in this protocol.