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 range18 Years
SexALL
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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.
✓. 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 \[MPDL3280A\]).
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)
✓. 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.