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Clinical Trial 18494

Cancer Type: Thoracic
Study Type: Treatment
NCT#: NCT02638090

Phase: Phase I/II
Principal Investigator: Gray, Jhanelle

Call 813-745-6100
or 1-800-679-0775 Learn More

Overview

Study Title

A Phase I/II Study of Pembrolizumab and Vorinostat in Patients with Immune Therapy Naïve and Immune Therapy Pretreated Stage IV NSCLC

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.

Objective

PRIMARY OBJECTIVES Phase 1 Escalation: Primary Objective: To determine the safety, tolerability and feasibility of concurrent administration of vorinostat and Pembrolizumab. Phase 1b Expansion (Single Arm, Pre-treated Cohort): Primary Objective: To determine whether concurrent administration of vorinostat and Pembrolizumab will be effective in NSCLC patients who have been previously exposed to anti-PD-1 or anti-PD-L1 therapy. Phase II (Randomized, Treatment Naïve Cohort): Primary Objective: To determine whether concurrent administration of vorinostat and Pembrolizumab is more effective than Pembrolizumab alone. SECONDARY OBJECTIVES Secondary Objectives (Phase 1 expansion and phase II Arms A and B): 1.To determine immunogenicity molecular profiles that correlate with outcome measures. 2.To determine immunogenicity profiles that correlate with resistance to therapy.

Treatments

Therapies

Immunotherapy; Therapy (NOS)

Medications

Pembrolizumab (Keytruda); SAHA (Vorinostat); Vorinostat (); Zolinza (Vorinostat); suberoylanilide hydroxamic acid (Vorinostat)

Inclusion Criteria

Willing and able to provide written informed consent/assent for the trial

Age ≥ 18 years 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. 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.

Also, 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%.

Performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale

Adequate organ function

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. Patients 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. Patients 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, ALKm RZOS1) 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 > Females of childbearing potential (FOCBP) should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication. FOCBP: 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: 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.

Exclusion Criteria

Receiving study therapy/participated in a study of investigational agent and received study therapy or used investigational device within 4 weeks of first dose of treatment.

Diagnosis of immunodeficiency or 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. Permitted to use topical, ocular, intra-articular, intranasal, and inhalational corticosteroids (with minimal systemic absorption). Physiologic replacement doses of systemic corticosteroids permitted, even if >= 10 mg/day prednisone equivalents. Brief course of corticosteroids for prophylaxis or for treatment of non-autoimmune conditions may be permitted.

Known history of TB (Mycobacterium tuberculosis)

Hypersensitivity to pembrolizumab, vorinostat or any of its excipients

Phase II Randomized Trial: Prior treatment with a PD1 or PDL1 inhibitor, anti-CTLA 4 antibody or any other antibody or drug that specifically targets immune checkpoint pathway. -Note: If 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 all participants in all phases, prior use of a vaccine for treatment of cancer is allowed.

Participants in 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¿)

Received thoracic radiation >30Gy within 6 months of the first dose of pembrolizumab

Taking any HDACi other than vorinostat

A prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1 or has not recovered from adverse events due to agents administered > 4 weeks earlier.

Had prior chemotherapy with 3 weeks, or targeted small molecule therapy or radiation therapy within 2 weeks prior to study Day 1 or and has not recovered from adverse events due to a previously administered agent. Note: Less than or equal to Grade 2 neuropathy may be an exception to this criterion. Note: Any grade alopecia are an exception to this criterion and may qualify for the study.

Received major surgery: Must have recovered adequately from toxicity and/or complications from the intervention prior to starting therapy

Known additional malignancy that is progressing or requires active treatment. Some exceptions: basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy, in situ cervical cancer

Known CNS metastases and/or carcinomatous meningitis. Previously treated brain metastases may be an exception if stable and specific other criteria are met.

Active autoimmune disease requiring systemic treatment in the past 2 years. Replacement therapy is not considered a form of systemic treatment. Some exceptions apply if specific criteria are met.

An active infection requiring systemic therapy

Pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial

Known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies)

Known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected).

Received a live vaccine within 30 days of planned start of study therapy.

Has a history of, or any evidence of active non-infectious pneumonitis that required or requires steroids.

Evidence of interstitial lung disease

Has a history of symptomatic (NYHA class II-IV) heart failure

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