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

NCT02718066 | Completed Phase 1 FDA Drug

• 1 other identifier: HBI-8000-302
• Study Type: interventional
• Target: 96
• Locations: 1 country
• Sites: 6

Brief Summary

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.

Conditions

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

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Determination of the Recommended for Phase 2 Dose (RP2D) (mg)

  Determination of the Recommended for Phase 2 Dose (RP2D) (mg)

  12 months

Secondary Outcomes (1)

• Efficacy Outcome: Response Rate (%).

  18 months

Study Arms (1)

HBI-8000 in combination with nivolumab

EXPERIMENTAL

HBI-8000 dose escalation 20mg, 30mg, 40mg, orally, twice weekly; in combination with Nivolumab 240mg intravenous infusions every 2 weeks for Phase 1b and in accordance with the manufacturer package insert and institution's prescribing practice for Phase 2.

Drug: HBI-8000 in combination with nivolumab

Interventions

HBI-8000 in combination with nivolumab DRUG

Phase 1b: HBI-8000, orally, twice a week, dose escalation 20mg, 30mg, 40mg; in combination with nivolumab 240mg intravenous infusion every 2 weeks. Phase 2: HBI-8000 MTD or 40mg; in combination with nivolumab in accordance with the manufacturer package insert and institution's prescribing practice.

Also known as: For HBI-8000: Chidamide, CS055; for nivolumab: OPDIVO

HBI-8000 in combination with nivolumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \. Adults at least 18 years of age. 2. Eastern Cooperative Oncology Group (ECOG) performance status ≤1. 3.
• Subjects with histopathologically or cytologically confirmed diagnosis of non-uveal 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).
• Subjects with histopathologically or cytologically confirmed diagnosis of non-uveal Melanoma, or NSCLC, for whom the use of nivolumab is indicated. With Protocol Amendment 5, subjects with NSCLC are not eligible for enrollment.
• Non-uveal melanoma and NSCLC patients whose disease has progressed after achieving SD for at least 3 months, PR or CR as the best response that has been documented by imaging studies (Phase 2 expansion).With Protocol Amendment 5, subjects with NSCLC are not eligible for enrollment.
• \. Subject must have at least one measurable target lesion as defined by Response Evaluation Criteria in Solid Tumors (RECIST) v.1.1. Melanoma subjects participating in the optional serial tumor biopsy sub-study must have tumor tissue available from a metastatic or unresectable site for PD-L1 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: 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.
• \. Life expectancy ≥12 weeks. 8. 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.

You may not qualify if:

• History of Grade 3 or above hypersensitivity reactions to other monoclonal antibodies.
• Subjects with 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, SBP \>160 or DBP \>100.
• Subjects with active brain metastasis; previously treated brain metastasis is allowed if it has been 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.
• 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.
• Use of other investigational agent (drug not marketed for any indication) within 28 days or at least 5 half-lives (whichever is shorter) 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, curatively treated prostate cancer with prostate-specific antigen (PSA) \<0.1 ng/mL.
• 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.

Sponsors & Collaborators

• HUYABIO International, LLC.: lead

Study Sites (6)

[Site 02] Mayo Clinic Arizona

Phoenix, Arizona, 85054, United States

Location

[Site 11] University of California, San Diego Medical Center

La Jolla, California, 92037, United States

Location

[Site 01] Hematology - Oncology Associates of the Treasure Coast

Port Saint Lucie, Florida, 34952, United States

Location

[Site 09] H. Lee Moffitt Cancer Center and Research Institute, Inc.

Tampa, Florida, 33612, United States

Location

[Site 13] Frederick Memorial Hospital d/b/a James M Stockman Cancer Institute

Frederick, Maryland, 21702, United States

Location

[Site 12] University of Texas M.D. Anderson Cancer Center - Investigational Cancer Therapeutics

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Melanoma; Carcinoma, Renal Cell; Carcinoma, Non-Small-Cell Lung

Interventions

HBI-8000; Nivolumab

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Nikhil I Khushalani, MD

  H. Lee Moffitt Cancer Center and Research Institute, Inc., Tampa, FL

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 15, 2016
• First Posted: March 24, 2016
• Study Start: August 1, 2016
• Primary Completion: September 1, 2023
• Study Completion: September 1, 2023
• Last Updated: November 9, 2023

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (6)