Clinical Trial 18874

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

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

  • Nikhil Khushalani

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.
  • Patients with histopathologically or cytologically confirmed diagnosis of Melanoma, Renal Cell Carcinoma (RCC) or Non-small Cell Lung Cancer (NSCLC), for whom the use of nivolumab is indicated.
  • Must have at least one measurable target lesion as defined by Response Evaluation Criteria in Solid Tumors (RECIST) v.1.1.
  • All prior chemotherapy, 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 14 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 ≥ 100x10^3/μL, Hemoglobin ≥ 9.0 g/dL, Creatinine ≤ 1.5 mg/dL, Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) ≤ 3 x ULN, Alkaline phosphatase ≤ 2.5 x Upper Limit of Normal (ULN) unless bone metastases present, Bilirubin ≤ 1.5 x ULN (unless known Gilbert's disease where it must be ≤ 3xULN)
  • Life expectancy ≥ 12 weeks.
  • A negative serum pregnancy test at screening for women of childbearing potential.
  • Are willing to abstain from heterosexual activity or practice physical barrier contraception prior to time of study entry to 6 months after the last day of treatment.
  • Have the ability to understand and the willingness to sign a written informed consent document.

  • Exclusion Criteria

  • Having received immune checkpoint inhibitors previously. Prior therapy with ipilimumab for melanoma is allowed.
  • History of Grade 3 or above hypersensitivity reactions to other monoclonal antibodies.
  • A history of a cardiovascular illness including: 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, Systolic Blood Pressure (SBP)> 160 or Diastolic Blood Pressure (DBP)>100.
  • Patients with brain metastasis, unless stable for 4 weeks or more and not requiring steroids.
  • Presence of leptomeningeal disease.
  • History of hemorrhagic diarrhea, inflammatory bowel disease or active uncontrolled peptic ulcer disease.
  • 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.
  • Infection with human immunodeficiency virus (HIV) or active hepatitis A, B (serum hepatitis B surface antigen positive), or C (serum hepatitis C RNA positive), tested at screening.
  • Concurrent medical condition requiring the use of immunosuppressive medications, or systemic steroids (prednisone dose is more than 10 mg/day or equivalent). Topical corticosteroids are allowed.
  • Use of other investigational drugs (drugs 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 (non-melanomatous skin cancer or carcinoma in situ of the cervix treated with curative intent is not exclusionary).
  • 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.