Pembro and Vorinostat for Patients With Stage IV Non-small Cell Lung Cancer (NSCLC)

NCT02638090 | Active Not Recruiting Phase 1 Results FDA Drug

• 1 other identifier: MCC-18494
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

Brief Summary

The main purpose of this study is to see whether the combination of two drugs called pembrolizumab and vorinostat can help people with advanced lung cancer. Researchers also want to find out if the combination of pembrolizumab and vorinostat is safe and tolerable. This study will compare the effects of the combination of two drugs called pembrolizumab and vorinostat with the effects of pembrolizumab alone. The U.S. Food and Drug Administration (FDA) has approved pembrolizumab for use to treat a deadly skin cancer called melanoma and lung cancer and vorinostat to treat some forms of blood and lymph node cancers.

Conditions

Lung Cancer; Non-small Cell Lung Cancer

Keywords

advanced lung cancer; immune therapy naive; immune therapy pre-treated; NSCLC; Stage IV lung cancer; pembrolizumab; vorinostat; immunogenicity

Outcome Measures

Primary Outcomes (1)

• Phase I: Maximum Tolerated Dose (MTD)

  The maximum tolerated dose (MTD) corresponding to a risk of dose limiting toxicity (DLT) occurring in 30% of patients. DLTs will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE v4.03). A DLT will be defined as any Grade 3 or higher toxicity that occurs during the DLT evaluation period. Toxicity that is clearly and directly related to the primary disease or to another etiology is excluded from this definition.

  Up to 12 months

Secondary Outcomes (1)

• Phase II: Progression Free Survival (PFS) Per Treatment Arm

  Up to 2 years

Other Outcomes (1)

• Phase II: Objective Response Rate (ORR) Per Treatment Arm

  Up to 2 years

Study Arms (4)

Phase I Dose Escalation

EXPERIMENTAL

Level 1: Vorinostat 200mg by mouth (PO) Daily; Pembrolizumab 200 mg intravenously (IV) every (Q) 3 weeks. Level 2: Vorinostat 400 mg PO Daily; Pembrolizumab 200 mg IV Q3 weeks

Drug: Vorinostat; Drug: Pembrolizumab

Phase Ib Expansion

EXPERIMENTAL

Pembrolizumab plus Vorinostat. Level 1: Maximum Tolerated Dose (MTD)

Drug: Vorinostat; Drug: Pembrolizumab

Arm A: Pembrolizumab

ACTIVE COMPARATOR

Pembrolizumab treatment only. Level 1: Pembrolizumab 200 mg Q3 wks

Drug: Pembrolizumab

Arm B: Pembrolizumab plus Vorinostat

ACTIVE COMPARATOR

Pembrolizumab plus Vorinostat treatment. Level 1: MTD

Drug: Vorinostat; Drug: Pembrolizumab

Interventions

Vorinostat DRUG

Administered per treatment arm guidelines.

Also known as: Zolinza

Arm B: Pembrolizumab plus Vorinostat; Phase I Dose Escalation; Phase Ib Expansion

Pembrolizumab DRUG

Administered per treatment arm guidelines.

Also known as: KEYTRUDA

Arm A: Pembrolizumab; Arm B: Pembrolizumab plus Vorinostat; Phase I Dose Escalation; Phase Ib Expansion

Eligibility Criteria

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

You may qualify if:

• Willing and able to provide written informed consent/assent for the trial.
• Be ≥ 18 years of age on day of signing informed consent.
• Have measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
• Have archival tissue where available. Those participants enrolled on the phase 1 escalation trial where archival tissue is not available will undergo a fresh biopsy where clinically feasible after discussion with the sponsor.
• In addition, participants enrolled on the phase 1 dose escalation, phase 1 expansion or Phase II trial must be willing and able to provide tissue from a newly obtained core or excisional biopsy of a tumor lesion.
• Randomized Phase II: Tumor proportional score of PD-L1 ≥1%.
• Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale.
• Demonstrate adequate organ function.
• Have a histologic or cytologic diagnosis of Stage IV non-small cell lung cancer (NSCLC).
• Phase I/IB (Pre-treated): Have progression from at least one prior line of therapy. Maintenance therapy following platinum doublet-based chemotherapy is not considered as a separate regimen of therapy. Participants who received platinum-containing adjuvant, neoadjuvant or definitive chemoradiation therapy given for locally advanced disease, and developed recurrent (local or metastatic) disease within 6 months of completing therapy are eligible for these arms. Participants with recurrent disease ≥ 6 months after completing a platinum-containing adjuvant, neoadjuvant or definitive chemoradiation therapy given for locally advanced disease, who also subsequently progressed during or after a systemic regimen given to treat the recurrence, must have received another treatment in the first-line metastatic setting.
• Randomized Phase II: Be treatment naïve in the stage IV setting, with the exception of participants whose tumors harbor an activation mutation (including but not limited to EGFR, ALK, ROS1) and were previously treated with targeted therapy. Participants who received platinum-containing adjuvant, neoadjuvant or definitive chemoradiation therapy given for locally advanced disease, and developed recurrent (local or metastatic) disease \< 6 months of completing therapy are ineligible for this arm. Subjects with recurrent disease ≥ 6 months after completing a platinum-containing adjuvant, neoadjuvant or definitive chemoradiation therapy given for locally advanced disease, who also subsequently progressed during or after a systemic regimen given to treat the recurrence, are eligible for this arm.
• Females of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication.
• Males should agree to use an adequate method of barrier contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy.

You may not qualify if:

• Is currently participating in and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment.
• Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy at doses ≥ 10 mg prednisone or any other form of systemic immunosuppressive therapy within 7 days prior to the first dose of trial treatment. Participants are permitted to use topical, ocular, intra-articular, intranasal, and inhalational corticosteroids (with minimal systemic absorption). Physiologic replacement doses of systemic corticosteroids are permitted, even if \>= 10 mg/day prednisone equivalents. A brief course (≤28 days) of corticosteroids for prophylaxis (e.g., contrast dye allergy) or for treatment of non-autoimmune conditions (e.g., delayed-type hypersensitivity reaction caused by contact allergen) is permitted.
• Has a known history of tuberculosis (TB) Disease (Mycobacterium tuberculosis).
• Hypersensitivity to pembrolizumab, vorinostat or any of its excipients.
• Participants enrolled on the phase II randomized trial, who have had prior treatment with a PD1 or PDL1 inhibitor, anti-CTLA 4 antibody or any other antibody or drug that specifically targets immune checkpoint pathway (i.e. not "immune therapy naïve"). -Note: For those enrolled in the phase I dose escalation, prior use of a PD1 or PDL1, anti-CTLA4 antibody or any other antibody or drug that specifically targets immune checkpoint pathway is allowed. For those enrolled in the phase IB, prior use of a PD1 or PDL1, anti-CTLA4 antibody or any other antibody or drug that specifically targets immune checkpoint pathway is required. For all participants in all phases, prior use of a vaccine for treatment of cancer is allowed.
• Participants enrolled in the phase Ib expansion who have never previously been treated with a PD1 or PDL1 inhibitor, anti-CTLA 4 antibody or any other antibody or drug that specifically targets immune checkpoint pathway in the past (i.e. not "pre-treated").
• Participants who have received thoracic radiation \>30Gy within 6 months of the first dose of pembrolizumab.
• Patients taking any HDACi other than vorinostat.
• Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
• Has had prior chemotherapy with 3 weeks, or targeted small molecule therapy or radiation therapy within 2 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent. Note: Patients with ≤ Grade 2 neuropathy are an exception to this criterion and may qualify for the study. Note: Patients with any grade alopecia are an exception to this criterion and may qualify for the study.
• If participant received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
• Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy, or in situ cervical cancer.
• Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Previously treated brain metastases may be an exception if stable and specific other criteria are met.
• Has active autoimmune disease that has required systemic treatment in the past 2 years. Replacement therapy is not considered a form of systemic treatment. Patients are permitted to enroll if they have vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger.
• Has an active infection requiring systemic therapy.

Sponsors & Collaborators

• H. Lee Moffitt Cancer Center and Research Institute: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

H. Lee Moffitt Cancer Center and Research Institute

Tampa, Florida, 33612, United States

Location

Related Links

• Moffitt Cancer Center Clinical Trials website

MeSH Terms

Conditions

Lung Neoplasms; Carcinoma, Non-Small-Cell Lung

Interventions

Vorinostat; pembrolizumab

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms

Intervention Hierarchy (Ancestors)

Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines; Hydroxamic Acids; Hydroxylamines; Hydroxy Acids; Carboxylic Acids

Results Point of Contact

• Title: Dr. Jhanelle E. Gray
• Organization: Moffitt Cancer Center

Jhanelle.Gray@Moffitt.org

813-745-7282

Study Officials

• Jhanelle Gray, M.D.

  H. Lee Moffitt Cancer Center and Research Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 18, 2015
• First Posted: December 22, 2015
• Study Start: March 22, 2016
• Primary Completion: January 21, 2024
• Study Completion (Estimated): July 1, 2026
• Last Updated: December 22, 2025
• Results First Posted: May 4, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)