Ph1b/2 Dose-Escalation Study of Entinostat With Pembrolizumab in Non-small Cell Lung Cancer (NSCL… (NCT02437136) | Clinical Trial Compass
CompletedPhase 1/2
Ph1b/2 Dose-Escalation Study of Entinostat With Pembrolizumab in Non-small Cell Lung Cancer (NSCLC) With Expansion Cohorts in NSCLC, Melanoma, and Colorectal Cancer (CRC)
United States191 participantsStarted 2015-08-26
Plain-language summary
The purpose of this study is to determine the safety and tolerability of entinostat used in combination with pembrolizumab in participants with NSCLC. Additionally, the purpose of the study is to assess how effective entinostat and pembrolizumab are in combination in participants with NSCLC, Melanoma, and Mismatch-Repair Proficient CRC.
Who can participate
Age range
18 Years
Sex
ALL
See this in plain English?
AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.
Inclusion criteria
. Has histologically- or pathologically-confirmed recurrent/metastatic NSCLC.
. If has adenocarcinoma, required to have previously been tested for anaplastic lymphoma kinase (ALK) rearrangements and epidermal growth factor receptor (EGFR) mutations, with results available for collection in this study, and, if positive, has been treated with prior epidermal growth factor receptor (EGFR) or ALK therapy.
. Received at least 1 chemotherapeutic regimen in the advanced/metastatic setting and experienced documented, unequivocal progressive disease by either RECIST 1.1 or clinical assessment. Additional requirements related to prior treatments applied and may have been dependent on mutational status.
. Participants with NSCLC enrolled in Cohort 1 of the Expansion Phase should not have been previously treated with a PD-1/PD-L1-blocking antibody.
. Previously treated with a PD-1/PD-L1-blocking antibody and experienced documented, unequivocal radiographic progression of disease by irRECIST, or similar criteria during or within 12 weeks after last dose of such treatment. Participants must have received at least 6 weeks of PD-1/PD-L1 therapy for Cohort 2 and at least 8 weeks of PD-1/PD-L1 therapy for Cohort 3.
Questions worth asking your doctor
Bring these to your next appointment. They're a starting point for a shared conversation — not a sign you qualify or a recommendation to enrol.
1Based on my diagnosis and history, is this trial worth exploring for me — or is there a standard treatment we should try first?
2What does this trial's phase tell us about how much is already known about its safety and benefit?
3What would taking part actually involve for me — visits, tests, time, and travel?
4What are the known and possible risks or side effects I should weigh, and how would they be monitored?
5If this trial isn't the right fit, what other options or trials would you suggest I look into?
Generated to help you prepare — always confirm anything about your own eligibility and care with the study team and your doctor.
Questions for the trial coordinator
The trial coordinator is the person who runs the study day to day. These cover the practical side — logistics, costs, and what taking part would actually mean for your life. The study team confirms whether you meet the criteria; these are questions to ask, not a sign you qualify.
1What does taking part actually involve week to week — how many visits, where, and how long does each one take?
2What costs are covered by the study, and what might I have to pay for myself, including travel, parking, or time off work?
3What happens during screening, and what happens if the study team confirms I don't meet the criteria after those tests?
4Who pays for the scans, blood work, and other tests the trial requires — the study, my insurance, or me?
5How will being in the trial affect my regular care, and will my own doctor stay informed and involved?
6Can I leave the trial at any point if I change my mind, and what would happen to my care if I do?
A starting point for the conversation — always confirm anything about your own eligibility, costs, and care with the study team and your doctor.
What they're measuring
1
Phase 2: Objective Response Rate (ORR), as Assessed Using Immune Response RECIST (irRECIST)
Timeframe: From date of randomization to date of progression (up to 765 days)
. In addition to having been previously treated with a PD-1/PD-L1-blocking antibody, has a histologically- or cytologically-confirmed diagnosis of unresectable or metastatic melanoma and experienced unequivocal progressive disease during treatment with a Serine/threonine-protein kinase B-Raf (BRAF) inhibitor if BRAF V600 mutation-positive. Treatment with BRAF inhibitor may occur after treatment with the checkpoint inhibitor.
. Received at least 1 chemotherapeutic regimen in the advanced/metastatic setting and experienced documented, unequivocal progressive disease by either RECIST 1.1 or clinical assessment. Must have documented mismatch repair-proficient colon cancer as determined by either immunohistochemistry for mismatch repair proteins or polymerase chain reaction (PCR)-based functional microsatellite instability. Participants with CRC enrolled in Cohort 4 should not have been previously treated with a PD-1/PD-L1-blocking antibody (that is, pembrolizumab, nivolumab, MEDI4736, or GNE PDL1 \[MPDL3280A\]).
. Aged 18 years or older on the day written informed consent is given.
Exclusion criteria
. Diagnosis of immunodeficiency or receiving systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug. The use of physiologic doses of corticosteroids may be approved after consultation with the Sponsor.
. Active autoimmune disease that has required systemic treatment in past 2 years (that is, with disease modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (for example, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment.
. History of interstitial lung disease (ILD).
. Allergy to benzamide or inactive components of entinostat.
. History of allergies to any active or inactive ingredients of pembrolizumab or severe hypersensitivity (≥Grade 3) to pembrolizumab.
. History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant's participation for the full duration of the study, or is not in the best interest of the patient to participate, in the opinion of the treating Investigator, including, but not limited to:
. Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study.
. Currently participating 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.