A Study of HBI-8000 (Tucidinostat) With Pembrolizumab in Non-Small Cell Lung Cancer (HBI-8000)

A Phase 2 Study to Assess the Safety and Efficacy of HBI-8000 in Combination With Pembrolizumab for Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC)

A Phase 2 Study to Assess the Safety and Efficacy of HBI-8000 in Combination with Pembrolizumab for Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC)

Study Overview

• Status: Terminated
• Conditions: Non Small Cell Lung Cancer
• Intervention / Treatment: Drug: HBI-8000 in combination with pembrolizumab

Detailed Description

This Phase 2 study evaluates HBI-8000, a histone deacetylase inhibitor (HDACi) in combination with pembrolizumab for the treatment of patients with advanced or metastatic non-small cell lung cancer who possess programmed death ligand 1 (PD-L1) expression Tumor Proportion Score (TPS) of 1% or greater.

The Treatment Phase allowed for up to 24 months of treatment (cycles were 21 days), providing the subject did not experience disease progression or unacceptable toxicity.

• Study Type: Interventional
• Enrollment (Actual): 5
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Goodyear, Arizona, United States, 85338
      • Western Regional Medical Center
  • California
    • Bakersfield, California, United States, 93309
      • CBCC Global Research, Inc at Comprehensive Blood and Cancer Center
  • Florida
    • Port Saint Lucie, Florida, United States, 34952
      • Hematology Oncology Associates of the Treasure Coast
  • Georgia
    • Newnan, Georgia, United States, 30265
      • Southeastern Regional Medical Center
  • Illinois
    • Zion, Illinois, United States, 60099
      • Midewestern Regional Medical Center, LLC
  • Kansas
    • Topeka, Kansas, United States, 66606
      • Cotton O'Neil Clinical Research Center
  • Maryland
    • Frederick, Maryland, United States, 21702
      • Frederick Health-JMSCI

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria

1. Adults at least 18 years of age.
2. Eastern Cooperative Oncology Group (ECOG) performance status ≤2.
3. Histopathologically confirmed diagnosis of NSCLC PD-L1 expression TPS ≥1% as determined by an FDA-approved test.
4. Have at least one measurable target lesion as defined by RECIST v.1.1.
5. Have not received immune checkpoint inhibitor therapy or more than one regimen of chemotherapy for advanced or metastatic disease. Subjects who have previously received immune checkpoint inhibitor therapy in the adjuvant or neoadjuvant setting may be allowed if disease progression occurred >6 months after the last dose and no clinically significant immune related toxicities leading to treatment discontinuation were observed.
6. Prior adjuvant or neoadjuvant systemic therapy with chemotherapy, EGFR or ALK mutation directed therapy must have been completed >4 weeks before Cycle 1 Day 1 (C1D1) dosing and recovered from all treatment related toxicity.
7. Any prior palliative radiotherapy or minor surgery must be completed at least 2 weeks and 1 week respectively before C1D1 dosing and recovered from all treatment related toxicities.

8. Adequate major organ functions at baseline as evidenced by laboratory findings within 14 days prior to C1D1 study drug administration as defined below:

   1. White blood cells (WBC) ≥3000/μL, neutrophils ≥1500/μL, platelets ≥100×103/μL, hemoglobin ≥9.0 g/dL, independent of transfusion.
   2. Serum creatinine ≤1.5 mg/dL, normal electrolytes, phosphorus, and calcium.
   3. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤3 × upper limit of normal (ULN), alkaline phosphatase ≤2.5 × ULN unless bone metastases present, bilirubin ≤1.5 × ULN (unless known Gilbert's disease where it must be ≤3 × ULN) and serum albumin ≥3.0 g/dL.
   4. Thyroid stimulating hormone (TSH) within normal limits.
9. Life expectancy ≥12 weeks.
10. A negative serum pregnancy test at baseline for women of childbearing potential (WOCBP).
11. Women of childbearing potential. (WOCBP), non-surgically sterile or premenopausal female capable of becoming pregnant and men (due to potential risk of drug exposure through the ejaculate) must agree to use an acceptable method of contraception while enrolled on this study, and for a period of 5 months following the last dose of treatment. Acceptable methods of birth control in this trial include 2 highly effective methods of birth control (as determined by the Investigator; one of the methods must be a barrier technique) or abstinence.
12. Have the ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria

1. History of Grade ≥3 hypersensitivity reactions to monoclonal antibodies.
2. History of a cardiovascular illness including: QT interval corrected by heart rate using Fridericia's correction formula (QTcF) >450 ms in male or >470 ms in female, congenital long QT syndrome, congestive heart failure (New York Heart Association Grade III or IV) (Protocol Appendix 2); unstable angina or myocardial infarction within the previous 6 months; or symptomatic cardiac arrhythmia despite medical management.
3. Uncontrolled hypertension, systolic blood pressure (SBP) >160 mmHg or diastolic blood pressure (DBP) >100 mmHg.
4. Central nervous system metastasis or leptomeningeal disease except when treatment for brain metastasis is completed >14 days prior to C1D1 and stable for ≥4 weeks on <10 mg daily prednisone or equivalent.
5. History of hemorrhagic diarrhea, inflammatory bowel disease, active uncontrolled peptic ulcer disease or bowel resection that affects absorption of orally administered drugs.
6. Recurrent pleural effusion requiring repetitive palliative thoracentesis within 3 months prior to study entry, except for subjects with a pleurex port.
7. Active, known, or suspected autoimmune disease, or history of immune-mediated toxicity leading to treatment discontinuation, except for type I diabetes mellitus, hypothyroidism only requiring hormone replacement or skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic therapy.
8. Active pneumonitis, history of non-infectious pneumonitis that required treatment with steroids, or history of interstitial lung disease.
9. Active uncontrolled bacterial, viral, or fungal infection requiring systemic therapy.
10. Known history of testing positive for human immunodeficiency virus (HIV), known acquired immunodeficiency syndrome (AIDS).
11. Active hepatitis B (hepatitis B surface antigen [HBVsAg] positive), or hepatitis C (HCV antibody test or serum hepatitis C ribonucleic acid [RNA] positive).
12. Received approved live vaccines within 30 days of planned C1D1. Inactivated viral vaccines or vaccines based on subviral component are allowed; however intranasal influenza vaccines (e.g., Flu-Mist) are not allowed. COVID-19 vaccination should be administered >7 days before C1D1.
13. Any condition requiring chronic systemic treatment with either corticosteroids (>10 mg daily prednisone equivalents) or other immunosuppressive medications, or steroids use within 14 days of study drug administration. Inhaled or topical steroids are permitted.
14. 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.
15. Pregnant or breast-feeding women.
16. Second malignancy unless in remission for 2 years; subjects with non-melanomatous skin cancer, carcinoma in situ of the cervix treated with curative intent, or curatively treated prostate cancer with prostate-specific antigen (PSA) <2.0 ng/mL can be included.
17. 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.
18. Unwilling or unable to comply with procedures required in this protocol.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: HBI-8000 in combination with pembrolizumab; HBI-8000 - 30 mg/dose, orally twice a week; Pembrolizumab - 400 mg every 6 weeks or 200 mg every 3 weeks according to Prescribing Information and institutional practice	Drug: HBI-8000 in combination with pembrolizumab; Participants will take 30 mg of HBI-8000 by mouth every 3-4 days on a twice weekly (BIW) schedule. Pembrolizumab will be administered at 400 mg IV every 6 weeks (Q6W) or 200 mg IV every 3 weeks (Q3W) according to Prescribing Information and institution's prescribing practice for pembrolizumab.; Other Names: pembrolizumab; Keytruda®; tucidinostat

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety and Tolerability of HBI-8000 When Administered in Combination With Standard Dose and Regimen of Pembrolizumab	Number of participants experiencing treatment-emergent adverse events (TEAEs) graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) v5.0	From the start of treatment until 30 days after the last dose of HBI-8000, up to approximately 13 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of response (DoR)	Time from 1st observation of objective response to disease progression	up to 38 months approximately
Disease Control Rate (DCR)	The proportion of subjects achieving complete response, partial response or stable disease	up to 38 months approximately
Progression-Free Survival (PFS)	Time from the first dose of HBI-8000 to disease progression or death	38 months
Safety and tolerability of HBI-8000 when administered in combination with standard dose and regimen of pembrolizumab	Number of participants experiencing treatment-emergent adverse events (TEAEs) graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) v5.0	From first enrolled up to 38 months, approximately

Collaborators and Investigators

• Sponsor: HUYABIO International, LLC.
• Investigators: Study Director: Gloria Lee, MD, PhD, HUYABIO International, LLC.

Study record dates

Study Major Dates

• Study Start (Actual): February 15, 2022
• Primary Completion (Actual): April 19, 2023
• Study Completion (Actual): April 19, 2023

Study Registration Dates

• First Submitted: November 19, 2021
• First Submitted That Met QC Criteria: November 19, 2021
• First Posted (Actual): December 2, 2021

Study Record Updates

• Last Update Posted (Actual): December 24, 2025
• Last Update Submitted That Met QC Criteria: December 23, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: NSCLC; Pembrolizumab; HBI-8000
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Carcinoma, Non-Small-Cell Lung; Antineoplastic Agents; Antineoplastic Agents, Immunological; pembrolizumab; N-(2-amino-5-fluorobenzyl)-4-(N-(pyridine-3-acrylyl)aminomethyl)benzamide; HBI-8000
• Other Study ID Numbers: HBI-8000-305

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No