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

Study Overview
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Brief Summary
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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.

Official Title
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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)

Conditions
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Non Small Cell Lung Cancer

Intervention / Treatment
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* Drug: HBI-8000 in combination with pembrolizumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histopathologically confirmed diagnosis of NSCLC with PD-L1 expression of ≥1% based on FDA-approved test No prior treatment with checkpoint inhibitors or more than one regimen of chemotherapy including epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) mutation directed therapy for advanced or metastatic disease Disease must have at least 1 measurable target lesion by RECIST 1.1 Adequate major organ functions as evidenced by laboratory findings within 14 days prior to first dose Eastern Cooperative Oncology Group (ECOG) ≤2 and must have a life expectancy of ≥12 weeks Exclusion Criteria: History of grade ≥3 hypersensitivity reactions to monoclonal antibodies Participation in another interventional clinical trial within 28 days or less than 5 half-lives of investigational agent before the first dose Recurrent pleural effusion requiring repetitive palliative thoracentesis within 3 months prior to study entry (except patients with a PleurX™ port) Active, known or suspected autoimmune disease or history of immune-mediated toxicity leading to discontinuation of previous checkpoint inhibitor treatment should be administered in (neo)adjuvant setting. Exceptions are for type I diabetes mellitus, hyperthyroidism requiring hormone-replacement or skin only disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic therapy Active pneumonitis, history of non-infectious pneumonitis that required treatment with steroids, or history of interstitial lung disease Received approved live vaccines within 30 days of planned first dose. Intranasal influenza vaccines (e.g. Flu-Mist) are not allowed, however inactivated viral vaccines or vaccines based on subviral component are allowed Any condition requiring chronic systemic treatment with either corticosteroids (>10 mg daily prednisone equivalents) or other immunosuppressive medications. And any steroids use within 14 days of first dose except for inhaled or topical steroids. Note: Other protocol-defined Inclusion/Exclusion criteria may apply

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HBI-8000 in combination with pembrolizumab<br> | Drug: HBI-8000 in combination with pembrolizumab<br>* 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.<br>* Other names: pembrolizumab;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate (ORR) | The proportion of subjects achieving complete response or partial response according to RECIST v1.1 | From enrollment until disease progression or unacceptable toxicity, assessed up to 38 months approximately | 

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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HBI-8000, Pembrolizumab, NSCLC