CompletedNCT02437136Updated Mar 20, 2025Results posted

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)

A Phase 1/2 interventional study of entinostat and pembrolizumab in Non-Small Cell Lung Cancer, Melanoma and Mismatch Repair-Proficient Colorectal Cancer, sponsored by Syndax Pharmaceuticals. Completed at 11 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2025-03-20.

Sponsored by Syndax Pharmaceuticals · Phase 1/2, Interventional, and Treatment

Phase: Phase 1/2
Study type: Interventional
Enrollment: 191
Allocation: Non-randomized
Ages: 18 Years and older
Sex: All

Study 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.

Conditions studied

Non-Small Cell Lung Cancer
Melanoma
Mismatch Repair-Proficient Colorectal Cancer

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In context

Lung Neoplasms

7,243 studies on the registry are indexed under Lung Neoplasms; 1,557 are open to participants now.

This study's enrollment of 191 is above the median of 60 across 5,295 interventional studies indexed under Lung Neoplasms.

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Lead sponsor

Syndax Pharmaceuticals is the lead sponsor of 29 studies on the registry; 3 are open to participants now.

Of its 11 completed or terminated interventional studies of FDA-regulated products, 6 (55%) have results posted.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 18 Years and older
Sexes eligible: All
Accepts healthy volunteers: No

Inclusion criteria

Participants with NSCLC:

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.
Participants in Expansion Phase, Cohorts 2 (NSCLC) and 3 (Melanoma):
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.
Participants with Melanoma:
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.
Participants in Expansion Phase, Cohort 4 (CRC):
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]).
All Participants:
Aged 18 years or older on the day written informed consent is given.
If has brain metastases, must have stable neurologic status following local therapy for at least 4 weeks without the use of steroids or on stable or decreasing dose of ≤10 milligrams (mg) daily prednisone (or equivalent), and must be without neurologic dysfunction that would confound the evaluation of neurologic and other AEs.
Evidence of locally recurrent or metastatic disease based on imaging studies within 28 days before the first study drug dose:
- At least 1 measurable lesion ≥20 mm by conventional techniques or ≥10 mm by spiral computed tomography (CT) scan or magnetic resonance imaging (MRI), with the last imaging performed within 28 days before the first study drug dose. If there is only 1 measurable lesion and it is located in previously irradiated field, it must have demonstrated unequivocal progression according to RECIST, version 1.1.
If receiving radiation therapy, has a 2-week washout period following completion of the treatment prior to receiving the first study drug dose and continues to have at least 1 measurable lesion, per above criterion.
Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
Has acceptable renal and hepatic function and stable hematologic and coagulation status.
Female participants must not be pregnant. If a participants is of childbearing potential, the participant must agree to use effective contraception, as defined in the protocol, during the study and for 120 days after the last dose of study drug.
If male, agrees to use an adequate method of contraception starting from the first dose of study drug through 120 days after the last dose of study drug.
Experienced resolution of toxic effect(s) of the most recent prior chemotherapy to Grade 1 or less (except alopecia). If participant underwent major surgery or radiation therapy of >30 gray (Gy), they must have recovered from the toxicity and/or complications from the intervention.
Willing to have fresh tumor samples collected during screening and at other time points designated as mandatory, per the Schedule of Study Assessments.
Able to understand and give written informed consent and comply with study procedures.

Exclusion criteria

Exclusion Criteria:

Participants meeting any of the following criteria are not eligible for study participation:

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:
- Myocardial infarction or arterial thromboembolic events within 6 months prior to baseline or severe or unstable angina, New York Heart Association (NYHA) Class III or IV disease, or a QTc interval > 470 milliseconds (msec).
- Uncontrolled heart failure or hypertension, uncontrolled diabetes mellitus, or uncontrolled systemic infection.
- Another known additional malignancy that is progressing or requires active treatment (excluding adequately treated basal cell carcinoma, squamous cell of the skin, cervical intraepithelial neoplasia [CIN]/cervical carcinoma in situ or melanoma in situ, or ductal carinoma in situ of the breast). Prior history of other cancer is allowed, as long as there is no active disease within the prior 5 years.
- Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis.
- Active infection requiring systemic therapy.
- Known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
Note: Participants with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging [using the identical imaging modality for each assessment, either MRI or CT scan] for at least 4 weeks prior to the first dose of study drug and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 2 weeks prior to the first dose of study drug or are on stable or decreasing dose of ≤10 mg daily prednisone (or equivalent). This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability.
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.
Received a live virus vaccination within 30 days of the first dose of treatment.
Prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to baseline or who has not recovered (that is, ≤Grade 1 or at baseline) from AEs due to agents administered more than 4 weeks earlier.
Prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study baseline or who has not recovered (that is, ≤Grade 1 or at baseline) from AEs due to a previously administered agent.
Note: Participants with ≤Grade 2 neuropathy or ≤Grade 2 alopecia are an exception to this criterion and may qualify for the study.
Note: If participant underwent major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
Received transfusion of blood products (including platelets or red blood cells) or administration of colony stimulating factors (including granulocyte-colony stimulating factor [G-CSF], granulocyte macrophage-colony stimulating factor [GM-CSF], or recombinant erythropoietin) within 4 weeks prior to the first dose of study drug.
Currently receiving treatment with any other agent listed on the prohibited medication list such as valproic acid, or other systemic cancer agents within 14 days of the first dose of treatment.
If female, is pregnant, breastfeeding, or expecting to conceive, or if male, expect to father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of study drug.
Known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies).
Known active hepatitis B (for example, hepatitis B surface antigen-reactive) or hepatitis C (for example, hepatitis C virus ribonucleic acid [qualitative]).
For CRC expansion cohort, no prior history of malignant bowel obstruction requiring hospitalization in the 6 months prior to enrollment
For the CRC expansion cohort, history of uncontrolled ascites, defined as symptomatic ascites and/or repeated paracenteses for symptom control in the past 3 months.

Study design

Phase: Phase 1 / Phase 2
Primary purpose: Treatment
Allocation: Non-randomized
Intervention model: Parallel assignment
Masking: None (open label)
Enrollment: 191 participants (actual)

Study arms

Experimental
Phase 1b (Dose Escalation): Entinostat 3 mg Weekly + Pembrolizumab
Participants with NSCLC will receive entinostat 3 mg administered orally weekly (Days 1, 8, and 15 of each 21-day cycle) along with pembrolizumab 200 mg via intravenous (IV) infusion once every 3 weeks (Day 1 of each 21-day cycle).
Drug: entinostat · Drug: pembrolizumab
Experimental
Phase 1b (Dose Escalation): Entinostat 5 mg Weekly + Pembrolizumab
Participants with NSCLC will receive entinostat 5 mg administered orally weekly (Days 1, 8, and 15 of each 21-day cycle) along with pembrolizumab 200 mg via IV infusion once every 3 weeks (Day 1 of each 21-day cycle).
Drug: entinostat · Drug: pembrolizumab
Experimental
Phase 1b (Dose Confirmation): Entinostat 5 mg Weekly + Pembrolizumab
Participants with NSCLC will receive entinostat 5 mg administered orally weekly (Days 1, 8, and 15 of each 21-day cycle) along with pembrolizumab 200 mg via IV infusion once every 3 weeks (Day 1 of each 21-day cycle).
Drug: entinostat · Drug: pembrolizumab
Experimental
Phase 2, Cohort 1: Entinostat 5 mg Weekly + Pembrolizumab
Participants with NSCLC with squamous cell or adenocarcinoma histology who had not been treated with a programmed cell death receptor-1 (PD-1)- or programmed cell death ligand-1 (PD-L1)-blocking antibody, will receive entinostat 5 mg administered orally weekly (Days 1, 8, and 15 of each 21-day cycle) along with pembrolizumab 200 mg via IV infusion once every 3 weeks (Day 1 of each 21-day cycle).
Drug: entinostat · Drug: pembrolizumab
Experimental
Phase 2, Cohort 2: Entinostat 5 mg Weekly + Pembrolizumab
Participants with NSCLC (any histology) who has previously been treated with and unequivocally progressed on either a PD-1- or PD-L1-blocking antibody, will receive entinostat 5 mg administered orally weekly (Days 1, 8, and 15 of each 21-day cycle) along with pembrolizumab 200 mg via IV infusion once every 3 weeks (Day 1 of each 21-day cycle).
Drug: entinostat · Drug: pembrolizumab
Experimental
Phase 2, Cohort 3: Entinostat 5 mg Weekly + Pembrolizumab
Participants with melanoma who has previously been treated with and unequivocally progressed on either a PD-1- or PD-L1-blocking antibody, will receive entinostat 5 mg administered orally weekly (Days 1, 8, and 15 of each 21-day cycle) along with pembrolizumab 200 mg via IV infusion once every 3 weeks (Day 1 of each 21-day cycle).
Drug: entinostat · Drug: pembrolizumab
Experimental
Phase 2, Cohort 4: Entinostat 5 mg Weekly + Pembrolizumab
Participants with CRC (mismatch repair-proficient) who had not been previously treated with a PD-1- or PD-L1-blocking antibody, received entinostat 5 mg administered orally weekly (Days 1, 8, and 15 of each 21-day cycle) along with pembrolizumab 200 mg via IV infusion once every 3 weeks (Day 1 of each 21-day cycle).
Drug: entinostat · Drug: pembrolizumab

Interventions

Drugentinostat
An orally available histone deacetylases inhibitor (HDACs)
Also known as: SNDX-275, MS-275
Drugpembrolizumab
A selective humanized monoclonal antibody (mAb)
Also known as: Keytruda, MK-3475, SCH 900475

What researchers measure

Primary outcomes

Phase 2: Objective Response Rate (ORR), as Assessed Using Immune Response RECIST (irRECIST)
The ORR was defined as the percentage of participants with confirmed complete response (CR) or partial response (PR). CR: Complete disappearance of all lesions (whether measurable or not) and no new lesions. All measurable lymph nodes also must have a reduction in short axis to \<10 millimeters (mm). PR: Sum of the diameters (longest for non-nodal lesions, shortest for nodal lesions) of target and new measurable lesions decreases ≥30%. For purposes of analysis, 1 month was considered to be 30.4375 days.
Time frame: From date of randomization to date of progression (up to 765 days)

Secondary outcomes

Phase 2: Clinical Benefit Rate (CBR), as Assessed Using irRECIST
The CBR was defined as the percentage of participants with a confirmed CR, PR, or stable disease (SD) lasting for at least 6 months. CR: Complete disappearance of all lesions (whether measurable or not) and no new lesions. All measurable lymph nodes also must have a reduction in short axis to \<10 mm. PR: Sum of the diameters (longest for non-nodal lesions, shortest for nodal lesions) of target and new measurable lesions decreases ≥30%. SD: Sum of the diameters (longest for nonnodal lesions, shortest for nodal lesions) of target and new measurable lesions neither CR, PR, (compared to baseline) or progressive disease (PD) (compared to nadir).
Time frame: 6 months
Phase 2: CBR, as Assessed Using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
The CBR was defined as the percentage of participants with a confirmed CR, PR, or SD lasting for at least 6 months. CR: Disappearance of all target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Disappearance of all non-target lesions and normalisation of tumour marker level. All lymph nodes must be non-pathological in size (\<10 mm short axis). PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.
Time frame: 6 months
Phase 2: Progression Free Survival (PFS), as Assessed Using irRECIST
PFS was defined as the number of months from randomization to PD or death due to any cause, whichever occurred first. PD: Sum of the diameters (longest for non-nodal lesions, shortest for nodal lesions) of target and new measurable lesions increases ≥20% (compared to nadir), confirmed by a repeat, consecutive observation at least 4 weeks from the date first documented. Number of participants without evidence of progression or death at Month 6 are reported.
Time frame: 6 months
Phase 2: PFS, as Assessed Using RECIST 1.1
PFS was defined as the number of months from randomization to PD or death due to any cause, whichever occurred first. PD: At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm; the appearance of one or more new lesions; and unequivocal progression of existing non-target lesions. Number of participants without evidence of progression or death at Month 6 are reported.
Time frame: 6 months
Phase 2: PFS Duration, as Determined by the Local Investigator Using irRECIST
PFS was defined as the number of months from randomization to PD or death due to any cause, whichever occurred first. PD: Sum of the diameters (longest for non-nodal lesions, shortest for nodal lesions) of target and new measurable lesions increases ≥20% (compared to nadir), confirmed by a repeat, consecutive observation at least 4 weeks from the date first documented. For purposes of analysis, 1 month was considered to be 30.4375 days.
Time frame: From date of randomization to PD or death due to any cause (up to 765 days)
Phase 2: PFS Duration, as Determined by the Local Investigator Using RECIST 1.1
PFS was defined as the number of months from randomization to PD or death due to any cause, whichever occurred first. PD: Sum of the diameters (longest for non-nodal lesions, shortest for nodal lesions) of target and new measurable lesions increases ≥20% (compared to nadir), confirmed by a repeat, consecutive observation at least 4 weeks from the date first documented. For purposes of analysis, 1 month was considered to be 30.4375 days.
Time frame: From date of randomization to PD or death due to any cause (up to 765 days)
Phase 2: Overall Survival
Overall survival was defined as the number of months from randomization to the date of death (due to any cause). For purposes of analysis, 1 month was considered to be 30.4375 days.
Time frame: From date of randomization to the date of death (up to 765 days)
Phase 2: Duration of Response, as Assessed Using irRECIST
Duration of response was defined as number of months from start date of CR or PR (whichever occurred first) and subsequently confirmed, to the first date that recurrent or progressive disease was documented. CR: Disappearance of all target lesions and any pathological lymph nodes (target or non-target) must have reduction in short axis to \<10 mm. Disappearance of all non-target lesions and normalisation of tumour marker level. All lymph nodes must be non-pathological in size (\<10 mm short axis). PR: At least a 30% decrease in sum of diameters of target lesions, taking as reference the baseline sum diameters. PD: At least a 20% increase in sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, sum must also demonstrate an absolute increase of ≥5 mm; appearance of one or more new lesions; and unequivocal progression of existing non-target lesions. For purposes of analysis, 1 month was considered to be 30.4375 days.
Time frame: From start date of CR or PR to date of progression (up to 765 days)
Phase 2: Duration of Response, as Assessed Using RECIST 1.1
Duration of response was defined as number of months from start date of CR or PR (whichever occurred first) and subsequently confirmed, to the first date that recurrent or progressive disease was documented. CR: Disappearance of all target lesions and any pathological lymph nodes (target or non-target) must have reduction in short axis to \<10 mm. Disappearance of all non-target lesions and normalisation of tumour marker level. All lymph nodes must be non-pathological in size (\<10 mm short axis). PR: At least a 30% decrease in sum of diameters of target lesions, taking as reference the baseline sum diameters. PD: At least a 20% increase in sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, sum must also demonstrate an absolute increase of ≥5 mm; appearance of one or more new lesions; and unequivocal progression of existing non-target lesions. For purposes of analysis, 1 month was considered to be 30.4375 days.
Time frame: From start date of CR or PR to date of progression (up to 765 days)
Phase 2: Time to Response, as Assessed Using irRECIST
Time to response was defined as the number of months from the randomization date to the first date the participant achieved a PR or CR (whichever response occurred first and was subsequently confirmed). CR: Disappearance of all target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Disappearance of all non-target lesions and normalisation of tumour marker level. All lymph nodes must be non-pathological in size (\<10 mm short axis). PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. For purposes of analysis, 1 month was considered to be 30.4375 days.
Time frame: From the date of randomization to date of PR or CR (up to 765 days)
Phase 2: Time to Response, as Assessed Using RECIST 1.1
Time to response was defined as the number of months from the randomization date to the first date the participant achieved a PR or CR (whichever response occurred first and was subsequently confirmed). CR: Disappearance of all target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Disappearance of all non-target lesions and normalisation of tumour marker level. All lymph nodes must be non-pathological in size (\<10 mm short axis). PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. For purposes of analysis, 1 month was considered to be 30.4375 days.
Time frame: From the date of randomization to date of PR or CR (up to 765 days)
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), AEs Resulting in the Permanent Discontinuation of Study Drug, and Death
An adverse event (AE) was defined as any untoward medical occurrence that develops or worsens in severity during the conduct of a clinical study and does not necessarily have a causal relationship to the study drug. SAEs included death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, or an important medical event that jeopardized the participant and required medical intervention to prevent 1 of the outcomes listed in this definition. TEAEs were defined as AEs that started on or after the first administration of study drug and within 30 days of the last administration of any study treatment. A summary of serious and non-serious AEs regardless of causality is located in 'Reported Adverse Events module'. For purposes of analysis, 1 month was considered to be 30.4375 days.
Time frame: From first dose of study drug up to 765 days
Phase 1b: Number of Participants With at Least One Dose Limiting Toxicities (DLTs)
A DLT was defined as the occurrence of any protocol-specified event in the first cycle of treatment (Day 1 through Day 21) of entinostat in combination with avelumab that were considered by the investigator to be at least possibly related to study drug.
Time frame: Day 1 through Day 21 (Cycle 1)
Phase 1b: Recommended Phase 2 Dose (RP2D)
The RP2D was determined in discussion with the Sponsor, Medical Monitor, and Dose Determination Phase Investigators. Additionally, observations related to immune correlates, and any cumulative toxicity observed after multiple cycles might be included in the rationale supporting the RP2D. The RP2D could be equal to or less than the preliminary maximum tolerated dose (MTD). The MTD was defined as the highest dose level at which \<33% of 6 participants experienced DLT.
Time frame: Day 1 through Day 21 (Cycle 1)

Results

Posted Mar 20, 2025

Participant flow

The study was conducted in 2 phases, a Dose Escalation/Confirmation Phase (Phase 1b) and an Expansion Phase (Phase 2).

Dose Escalation/Confirmation (Phase 1b)

Participant flow — Dose Escalation/Confirmation (Phase 1b)
Milestone	Phase 1b (Dose Escalation): Entinostat 3 mg Weekly + Pembrolizumab	Phase 1b (Dose Escalation): Entinostat 5 mg Weekly + Pembrolizumab	Phase 1b (Dose Confirmation): Entinostat 5 mg Weekly + Pembrolizumab
Started	6	7	9
Received at least 1 dose of study drug	6	7	9
Completed	2	7	9
Not completed	4	0	0
Withdrew: Death	4	0	0

Expansion (Phase 2)

Participant flow — Expansion (Phase 2)
Milestone	Phase 2, Cohort 1: Entinostat 5 mg Weekly + Pembrolizumab	Phase 2, Cohort 2: Entinostat 5 mg Weekly + Pembrolizumab	Phase 2, Cohort 3: Entinostat 5 mg Weekly + Pembrolizumab	Phase 2, Cohort 4: Entinostat 5 mg Weekly + Pembrolizumab
Started	18	76	53	38
Received at least 1 dose of study drug	18	76	53	38
Completed	5	11	17	10
Not completed	13	65	36	28
Withdrew: Death	6	37	29	24
Withdrew: Withdrawal by subject	7	25	4	2
Withdrew: Lost to follow-up	0	3	3	2

Outcome measures

PrimaryPhase 2: Objective Response Rate (ORR), as Assessed Using Immune Response RECIST (irRECIST)

The ORR was defined as the percentage of participants with confirmed complete response (CR) or partial response (PR). CR: Complete disappearance of all lesions (whether measurable or not) and no new lesions. All measurable lymph nodes also must have a reduction in short axis to \<10 millimeters (mm). PR: Sum of the diameters (longest for non-nodal lesions, shortest for nodal lesions) of target and new measurable lesions decreases ≥30%. For purposes of analysis, 1 month was considered to be 30.4375 days.

Time frame:: From date of randomization to date of progression (up to 765 days)
Reported as:: Number · percentage of participants

Phase 2: Objective Response Rate (ORR), as Assessed Using Immune Response RECIST (irRECIST)
percentage of participants	Phase 2, Cohort 1: Entinostat 5 mg Weekly + Pembrolizumab	Phase 2, Cohort 2: Entinostat 5 mg Weekly + Pembrolizumab	Phase 2, Cohort 3: Entinostat 5 mg Weekly + Pembrolizumab	Phase 2, Cohort 4: Entinostat 5 mg Weekly + Pembrolizumab
Phase 2: Objective Response Rate (ORR), as Assessed Using Immune Response RECIST (irRECIST)	22.2 (6.4 to 47.6)	9.2 (3.8 to 18.1)	18.9 (9.4 to 32.0)	5.4 (0.7 to 18.2)

SecondaryPhase 2: Clinical Benefit Rate (CBR), as Assessed Using irRECIST

The CBR was defined as the percentage of participants with a confirmed CR, PR, or stable disease (SD) lasting for at least 6 months. CR: Complete disappearance of all lesions (whether measurable or not) and no new lesions. All measurable lymph nodes also must have a reduction in short axis to \<10 mm. PR: Sum of the diameters (longest for non-nodal lesions, shortest for nodal lesions) of target and new measurable lesions decreases ≥30%. SD: Sum of the diameters (longest for nonnodal lesions, shortest for nodal lesions) of target and new measurable lesions neither CR, PR, (compared to baseline) or progressive disease (PD) (compared to nadir).

Time frame:: 6 months
Reported as:: Number · percentage of participants

Phase 2: Clinical Benefit Rate (CBR), as Assessed Using irRECIST
percentage of participants	Phase 2, Cohort 1: Entinostat 5 mg Weekly + Pembrolizumab	Phase 2, Cohort 2: Entinostat 5 mg Weekly + Pembrolizumab	Phase 2, Cohort 3: Entinostat 5 mg Weekly + Pembrolizumab	Phase 2, Cohort 4: Entinostat 5 mg Weekly + Pembrolizumab
Phase 2: Clinical Benefit Rate (CBR), as Assessed Using irRECIST	33.3 (13.3 to 59.0)	14.5 (7.5 to 24.4)	35.8 (23.1 to 50.2)	8.1 (1.7 to 21.9)

SecondaryPhase 2: CBR, as Assessed Using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)

The CBR was defined as the percentage of participants with a confirmed CR, PR, or SD lasting for at least 6 months. CR: Disappearance of all target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Disappearance of all non-target lesions and normalisation of tumour marker level. All lymph nodes must be non-pathological in size (\<10 mm short axis). PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.

Time frame:: 6 months
Reported as:: Number · percentage of participants

Phase 2: CBR, as Assessed Using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
percentage of participants	Phase 2, Cohort 1: Entinostat 5 mg Weekly + Pembrolizumab	Phase 2, Cohort 2: Entinostat 5 mg Weekly + Pembrolizumab	Phase 2, Cohort 3: Entinostat 5 mg Weekly + Pembrolizumab	Phase 2, Cohort 4: Entinostat 5 mg Weekly + Pembrolizumab
Phase 2: CBR, as Assessed Using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)	22.2 (6.4 to 47.6)	14.5 (7.5 to 24.4)	30.2 (18.3 to 44.3)	2.7 (0.1 to 14.2)

SecondaryPhase 2: Progression Free Survival (PFS), as Assessed Using irRECIST

PFS was defined as the number of months from randomization to PD or death due to any cause, whichever occurred first. PD: Sum of the diameters (longest for non-nodal lesions, shortest for nodal lesions) of target and new measurable lesions increases ≥20% (compared to nadir), confirmed by a repeat, consecutive observation at least 4 weeks from the date first documented. Number of participants without evidence of progression or death at Month 6 are reported.

Time frame:: 6 months
Reported as:: Count of participants · Participants

Phase 2: Progression Free Survival (PFS), as Assessed Using irRECIST
Participants	Phase 2, Cohort 1: Entinostat 5 mg Weekly + Pembrolizumab	Phase 2, Cohort 2: Entinostat 5 mg Weekly + Pembrolizumab	Phase 2, Cohort 3: Entinostat 5 mg Weekly + Pembrolizumab	Phase 2, Cohort 4: Entinostat 5 mg Weekly + Pembrolizumab
Phase 2: Progression Free Survival (PFS), as Assessed Using irRECIST	3	17	20	3

SecondaryPhase 2: PFS, as Assessed Using RECIST 1.1

PFS was defined as the number of months from randomization to PD or death due to any cause, whichever occurred first. PD: At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm; the appearance of one or more new lesions; and unequivocal progression of existing non-target lesions. Number of participants without evidence of progression or death at Month 6 are reported.

Time frame:: 6 months
Reported as:: Count of participants · Participants

Phase 2: PFS, as Assessed Using RECIST 1.1
Participants	Phase 2, Cohort 1: Entinostat 5 mg Weekly + Pembrolizumab	Phase 2, Cohort 2: Entinostat 5 mg Weekly + Pembrolizumab	Phase 2, Cohort 3: Entinostat 5 mg Weekly + Pembrolizumab	Phase 2, Cohort 4: Entinostat 5 mg Weekly + Pembrolizumab
Phase 2: PFS, as Assessed Using RECIST 1.1	3	17	17	2

SecondaryPhase 2: PFS Duration, as Determined by the Local Investigator Using irRECIST

PFS was defined as the number of months from randomization to PD or death due to any cause, whichever occurred first. PD: Sum of the diameters (longest for non-nodal lesions, shortest for nodal lesions) of target and new measurable lesions increases ≥20% (compared to nadir), confirmed by a repeat, consecutive observation at least 4 weeks from the date first documented. For purposes of analysis, 1 month was considered to be 30.4375 days.

Time frame:: From date of randomization to PD or death due to any cause (up to 765 days)
Reported as:: Median · months

Phase 2: PFS Duration, as Determined by the Local Investigator Using irRECIST
months	Phase 2, Cohort 1: Entinostat 5 mg Weekly + Pembrolizumab	Phase 2, Cohort 2: Entinostat 5 mg Weekly + Pembrolizumab	Phase 2, Cohort 3: Entinostat 5 mg Weekly + Pembrolizumab	Phase 2, Cohort 4: Entinostat 5 mg Weekly + Pembrolizumab
Phase 2: PFS Duration, as Determined by the Local Investigator Using irRECIST	2.76 (1.18 to 4.07)	2.83 (1.51 to 4.14)	4.40 (2.79 to 6.97)	1.91 (1.38 to 2.79)

SecondaryPhase 2: PFS Duration, as Determined by the Local Investigator Using RECIST 1.1

PFS was defined as the number of months from randomization to PD or death due to any cause, whichever occurred first. PD: Sum of the diameters (longest for non-nodal lesions, shortest for nodal lesions) of target and new measurable lesions increases ≥20% (compared to nadir), confirmed by a repeat, consecutive observation at least 4 weeks from the date first documented. For purposes of analysis, 1 month was considered to be 30.4375 days.

Time frame:: From date of randomization to PD or death due to any cause (up to 765 days)
Reported as:: Median · months

Phase 2: PFS Duration, as Determined by the Local Investigator Using RECIST 1.1
months	Phase 2, Cohort 1: Entinostat 5 mg Weekly + Pembrolizumab	Phase 2, Cohort 2: Entinostat 5 mg Weekly + Pembrolizumab	Phase 2, Cohort 3: Entinostat 5 mg Weekly + Pembrolizumab	Phase 2, Cohort 4: Entinostat 5 mg Weekly + Pembrolizumab
Phase 2: PFS Duration, as Determined by the Local Investigator Using RECIST 1.1	2.76 (1.18 to 4.07)	2.69 (1.48 to 4.07)	2.96 (1.45 to 6.24)	1.91 (1.38 to 2.79)

SecondaryPhase 2: Overall Survival

Overall survival was defined as the number of months from randomization to the date of death (due to any cause). For purposes of analysis, 1 month was considered to be 30.4375 days.

Time frame:: From date of randomization to the date of death (up to 765 days)
Reported as:: Median · months

Phase 2: Overall Survival
months	Phase 2, Cohort 1: Entinostat 5 mg Weekly + Pembrolizumab	Phase 2, Cohort 2: Entinostat 5 mg Weekly + Pembrolizumab	Phase 2, Cohort 3: Entinostat 5 mg Weekly + Pembrolizumab	Phase 2, Cohort 4: Entinostat 5 mg Weekly + Pembrolizumab
Phase 2: Overall Survival	25.20 (3.58 to NA)	11.73 (7.56 to 13.37)	12.52 (8.51 to 28.25)	9.79 (6.11 to 14.36)

SecondaryPhase 2: Duration of Response, as Assessed Using irRECIST

Duration of response was defined as number of months from start date of CR or PR (whichever occurred first) and subsequently confirmed, to the first date that recurrent or progressive disease was documented. CR: Disappearance of all target lesions and any pathological lymph nodes (target or non-target) must have reduction in short axis to \<10 mm. Disappearance of all non-target lesions and normalisation of tumour marker level. All lymph nodes must be non-pathological in size (\<10 mm short axis). PR: At least a 30% decrease in sum of diameters of target lesions, taking as reference the baseline sum diameters. PD: At least a 20% increase in sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, sum must also demonstrate an absolute increase of ≥5 mm; appearance of one or more new lesions; and unequivocal progression of existing non-target lesions. For purposes of analysis, 1 month was considered to be 30.4375 days.

Time frame:: From start date of CR or PR to date of progression (up to 765 days)
Reported as:: Median · months

Phase 2: Duration of Response, as Assessed Using irRECIST
months	Phase 2, Cohort 1: Entinostat 5 mg Weekly + Pembrolizumab	Phase 2, Cohort 2: Entinostat 5 mg Weekly + Pembrolizumab	Phase 2, Cohort 3: Entinostat 5 mg Weekly + Pembrolizumab	Phase 2, Cohort 4: Entinostat 5 mg Weekly + Pembrolizumab
Phase 2: Duration of Response, as Assessed Using irRECIST	15.61 (1.18 to NA)	10.10 (3.94 to NA)	25.49 (4.60 to 25.49)	7.33 (NA to NA)

SecondaryPhase 2: Duration of Response, as Assessed Using RECIST 1.1

Time frame:: From start date of CR or PR to date of progression (up to 765 days)
Reported as:: Median · months

Phase 2: Duration of Response, as Assessed Using RECIST 1.1
months	Phase 2, Cohort 1: Entinostat 5 mg Weekly + Pembrolizumab	Phase 2, Cohort 2: Entinostat 5 mg Weekly + Pembrolizumab	Phase 2, Cohort 3: Entinostat 5 mg Weekly + Pembrolizumab	Phase 2, Cohort 4: Entinostat 5 mg Weekly + Pembrolizumab
Phase 2: Duration of Response, as Assessed Using RECIST 1.1	NA (NA to NA)	10.14 (3.94 to NA)	25.49 (NA to NA)	—

SecondaryPhase 2: Time to Response, as Assessed Using irRECIST

Time to response was defined as the number of months from the randomization date to the first date the participant achieved a PR or CR (whichever response occurred first and was subsequently confirmed). CR: Disappearance of all target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Disappearance of all non-target lesions and normalisation of tumour marker level. All lymph nodes must be non-pathological in size (\<10 mm short axis). PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. For purposes of analysis, 1 month was considered to be 30.4375 days.

Time frame:: From the date of randomization to date of PR or CR (up to 765 days)
Reported as:: Median · months

Phase 2: Time to Response, as Assessed Using irRECIST
months	Phase 2, Cohort 1: Entinostat 5 mg Weekly + Pembrolizumab	Phase 2, Cohort 2: Entinostat 5 mg Weekly + Pembrolizumab	Phase 2, Cohort 3: Entinostat 5 mg Weekly + Pembrolizumab	Phase 2, Cohort 4: Entinostat 5 mg Weekly + Pembrolizumab
Phase 2: Time to Response, as Assessed Using irRECIST	4.30 (2.69 to 9.63)	2.83 (2.69 to 5.49)	1.95 (1.18 to 2.79)	4.17 (2.79 to 5.55)

SecondaryPhase 2: Time to Response, as Assessed Using RECIST 1.1

Time frame:: From the date of randomization to date of PR or CR (up to 765 days)
Reported as:: Median · months

Phase 2: Time to Response, as Assessed Using RECIST 1.1
months	Phase 2, Cohort 1: Entinostat 5 mg Weekly + Pembrolizumab	Phase 2, Cohort 2: Entinostat 5 mg Weekly + Pembrolizumab	Phase 2, Cohort 3: Entinostat 5 mg Weekly + Pembrolizumab	Phase 2, Cohort 4: Entinostat 5 mg Weekly + Pembrolizumab
Phase 2: Time to Response, as Assessed Using RECIST 1.1	4.29 (2.69 to 5.88)	2.83 (2.69 to 5.49)	1.95 (1.18 to 2.79)	—

SecondaryNumber of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), AEs Resulting in the Permanent Discontinuation of Study Drug, and Death

An adverse event (AE) was defined as any untoward medical occurrence that develops or worsens in severity during the conduct of a clinical study and does not necessarily have a causal relationship to the study drug. SAEs included death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, or an important medical event that jeopardized the participant and required medical intervention to prevent 1 of the outcomes listed in this definition. TEAEs were defined as AEs that started on or after the first administration of study drug and within 30 days of the last administration of any study treatment. A summary of serious and non-serious AEs regardless of causality is located in 'Reported Adverse Events module'. For purposes of analysis, 1 month was considered to be 30.4375 days.

Time frame:: From first dose of study drug up to 765 days
Reported as:: Count of participants · Participants

Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), AEs Resulting in the Permanent Discontinuation of Study Drug, and Death
Participants	Phase 1b (Dose Escalation): Entinostat 3 mg Weekly + Pembrolizumab	Phase 1b (Dose Escalation): Entinostat 5 mg Weekly + Pembrolizumab	Phase 1b (Dose Confirmation): Entinostat 5 mg Weekly + Pembrolizumab	Phase 2, Cohort 1: Entinostat 5 mg Weekly + Pembrolizumab	Phase 2, Cohort 2: Entinostat 5 mg Weekly + Pembrolizumab	Phase 2, Cohort 3: Entinostat 5 mg Weekly + Pembrolizumab	Phase 2, Cohort 4: Entinostat 5 mg Weekly + Pembrolizumab
TEAEs	6	7	9	18	75	53	37
SAEs	4	4	2	10	33	24	14
AEs Resulting in the Permanent Discontinuation of Study Drug	1	2	1	7	19	8	7
AEs Resulting in Death	1	0	1	3	3	2	1

SecondaryPhase 1b: Number of Participants With at Least One Dose Limiting Toxicities (DLTs)

A DLT was defined as the occurrence of any protocol-specified event in the first cycle of treatment (Day 1 through Day 21) of entinostat in combination with avelumab that were considered by the investigator to be at least possibly related to study drug.

Time frame:: Day 1 through Day 21 (Cycle 1)
Reported as:: Count of participants · Participants

Phase 1b: Number of Participants With at Least One Dose Limiting Toxicities (DLTs)
Participants	Phase 1b (Dose Escalation): Entinostat 3 mg Weekly + Pembrolizumab	Phase 1b (Dose Escalation): Entinostat 5 mg Weekly + Pembrolizumab	Phase 1b (Dose Confirmation): Entinostat 5 mg Weekly + Pembrolizumab
Phase 1b: Number of Participants With at Least One Dose Limiting Toxicities (DLTs)	0	1	0

SecondaryPhase 1b: Recommended Phase 2 Dose (RP2D)

The RP2D was determined in discussion with the Sponsor, Medical Monitor, and Dose Determination Phase Investigators. Additionally, observations related to immune correlates, and any cumulative toxicity observed after multiple cycles might be included in the rationale supporting the RP2D. The RP2D could be equal to or less than the preliminary maximum tolerated dose (MTD). The MTD was defined as the highest dose level at which \<33% of 6 participants experienced DLT.

Time frame:: Day 1 through Day 21 (Cycle 1)
Reported as:: Number · mg

Phase 1b: Recommended Phase 2 Dose (RP2D)
mg	Phase 1b: Entinostat 3 mg or 5 mg Weekly + Pembrolizumab
Phase 1b: Recommended Phase 2 Dose (RP2D)	5

Adverse events

Collected over From first dose of study drug up to 765 days. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Phase 1b (Dose Escalation): Entinostat 3 mg Weekly + Pembrolizumab	6/6 (100%)	4/6 (66.7%)	6/6 (100%)
Phase 1b (Dose Escalation): Entinostat 5 mg Weekly + Pembrolizumab	0/7 (0%)	4/7 (57.1%)	7/7 (100%)
Phase 1b (Dose Confirmation): Entinostat 5 mg Weekly + Pembrolizumab	1/9 (11.1%)	2/9 (22.2%)	9/9 (100%)
Phase 2, Cohort 1: Entinostat 5 mg Weekly + Pembrolizumab	8/18 (44.4%)	10/18 (55.6%)	18/18 (100%)
Phase 2, Cohort 2: Entinostat 5 mg Weekly + Pembrolizumab	41/76 (53.9%)	33/76 (43.4%)	75/76 (98.7%)
Phase 2, Cohort 3: Entinostat 5 mg Weekly + Pembrolizumab	31/53 (58.5%)	24/53 (45.3%)	52/53 (98.1%)
Phase 2, Cohort 4: Entinostat 5 mg Weekly + Pembrolizumab	25/38 (65.8%)	14/38 (36.8%)	37/38 (97.4%)

Most frequent serious events

Showing 10 of 95

Most frequent serious events
Event	Phase 1b (Dose Escalation): Entinostat 3 mg Weekly + Pembrolizumab	Phase 1b (Dose Escalation): Entinostat 5 mg Weekly + Pembrolizumab	Phase 1b (Dose Confirmation): Entinostat 5 mg Weekly + Pembrolizumab	Phase 2, Cohort 1: Entinostat 5 mg Weekly + Pembrolizumab	Phase 2, Cohort 2: Entinostat 5 mg Weekly + Pembrolizumab	Phase 2, Cohort 3: Entinostat 5 mg Weekly + Pembrolizumab	Phase 2, Cohort 4: Entinostat 5 mg Weekly + Pembrolizumab
Pleural effusionRespiratory, thoracic and mediastinal disorders	1/6	0/7	0/9	0/18	2/76	1/53	1/38
PneumoniaInfections and infestations	1/6	0/7	0/9	0/18	1/76	0/53	1/38
Pericardial effusionCardiac disorders	1/6	0/7	0/9	1/18	1/76	0/53	0/38
DeathGeneral disorders	1/6	0/7	0/9	0/18	0/76	0/53	0/38
Autoimmune hepatitisHepatobiliary disorders	1/6	0/7	0/9	0/18	0/76	2/53	0/38
Urinary tract obstructionRenal and urinary disorders	1/6	0/7	0/9	0/18	0/76	0/53	0/38
Pulmonary haemorrhageRespiratory, thoracic and mediastinal disorders	0/6	1/7	1/9	2/18	1/76	0/53	0/38
Atrial fibrillationCardiac disorders	0/6	1/7	0/9	1/18	1/76	2/53	0/38
AnaemiaBlood and lymphatic system disorders	0/6	1/7	0/9	1/18	3/76	1/53	1/38
HemiparesisNervous system disorders	0/6	1/7	0/9	1/18	0/76	0/53	0/38

Most frequent other events

Showing 10 of 390

Most frequent other events
Event	Phase 1b (Dose Escalation): Entinostat 3 mg Weekly + Pembrolizumab	Phase 1b (Dose Escalation): Entinostat 5 mg Weekly + Pembrolizumab	Phase 1b (Dose Confirmation): Entinostat 5 mg Weekly + Pembrolizumab	Phase 2, Cohort 1: Entinostat 5 mg Weekly + Pembrolizumab	Phase 2, Cohort 2: Entinostat 5 mg Weekly + Pembrolizumab	Phase 2, Cohort 3: Entinostat 5 mg Weekly + Pembrolizumab	Phase 2, Cohort 4: Entinostat 5 mg Weekly + Pembrolizumab
FatigueGeneral disorders	2/6	6/7	6/9	14/18	36/76	29/53	22/38
NauseaGastrointestinal disorders	2/6	1/7	3/9	5/18	21/76	30/53	9/38
Decreased appetiteMetabolism and nutrition disorders	3/6	0/7	5/9	3/18	27/76	16/53	10/38
Musculoskeletal and connective tissue disordersRespiratory, thoracic and mediastinal disorders	2/6	0/7	0/9	10/18	34/76	24/53	17/38
HypophosphataemiaMetabolism and nutrition disorders	0/6	3/7	0/9	5/18	19/76	4/53	4/38
CoughRespiratory, thoracic and mediastinal disorders	2/6	3/7	3/9	7/18	15/76	10/53	6/38
MyalgiaRespiratory, thoracic and mediastinal disorders	1/6	3/7	1/9	4/18	4/76	7/53	6/38
PruritusSkin and subcutaneous tissue disorders	1/6	3/7	1/9	4/18	6/76	12/53	4/38
DyspnoeaRespiratory, thoracic and mediastinal disorders	2/6	1/7	0/9	3/18	17/76	21/53	8/38
DiarrhoeaGastrointestinal disorders	2/6	1/7	3/9	5/18	25/76	20/53	13/38

Baseline characteristics

Safety analysis set included all participants who received at least 1 dose of either study drug, entinostat, or pembrolizumab.

Age, Customized
Age, Customized(Participants)	Phase 1b (Dose Escalation): Entinostat 3 mg Weekly + Pembrolizumab	Phase 2, Cohort 1: Entinostat 5 mg Weekly + Pembrolizumab	Phase 2, Cohort 2: Entinostat 5 mg Weekly + Pembrolizumab	Phase 2, Cohort 3: Entinostat 5 mg Weekly + Pembrolizumab	Phase 2, Cohort 4: Entinostat 5 mg Weekly + Pembrolizumab	Total
Age — 44 years and younger	0	1	1	6	6	14
Age — 45 to 64 years	1	7	35	23	24	90
Age — 65 to 74 years	5	7	25	14	6	57
Age — 75 years and older	0	3	15	10	2	30

Sex: Female, Male
Sex: Female, Male(Participants)	Phase 1b (Dose Escalation): Entinostat 3 mg Weekly + Pembrolizumab	Phase 2, Cohort 1: Entinostat 5 mg Weekly + Pembrolizumab	Phase 2, Cohort 2: Entinostat 5 mg Weekly + Pembrolizumab	Phase 2, Cohort 3: Entinostat 5 mg Weekly + Pembrolizumab	Phase 2, Cohort 4: Entinostat 5 mg Weekly + Pembrolizumab	Total
Female	1	8	36	21	14	80
Male	5	10	40	32	24	111

Race (NIH/OMB)
Race (NIH/OMB)(Participants)	Phase 1b (Dose Escalation): Entinostat 3 mg Weekly + Pembrolizumab	Phase 2, Cohort 1: Entinostat 5 mg Weekly + Pembrolizumab	Phase 2, Cohort 2: Entinostat 5 mg Weekly + Pembrolizumab	Phase 2, Cohort 3: Entinostat 5 mg Weekly + Pembrolizumab	Phase 2, Cohort 4: Entinostat 5 mg Weekly + Pembrolizumab	Total
American Indian or Alaska Native	0	0	0	0	0	0
Asian	0	2	2	1	0	5
Native Hawaiian or Other Pacific Islander	0	0	0	0	0	0
Black or African American	1	0	3	3	5	12
White	4	15	66	47	32	164
More than one race	0	0	0	0	0	0
Unknown or Not Reported	1	1	5	2	1	10

Study locations

11 sites

Yale University
New Haven, Connecticut 06519, United States
Emory University
Atlanta, Georgia 30322, United States
University of Maryland, Marlene and Stewart Greenbaum Cancer Center
Baltimore, Maryland 21201, United States
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Baltimore, Maryland 21231, United States
Dana Farber Cancer Institution
Boston, Massachusetts 02215, United States
Roswell Park Cancer Institute
Buffalo, New York 14263, United States
Memorial Sloan Kettering Cancer Center
New York, New York 10065, United States
The University of North Carolina at Chapel Hill
Chapel Hill, North Carolina 27599, United States
St Luke's University Health Network
Easton, Pennsylvania 18045, United States
Sarah Cannon Research Institute
Nashville, Tennessee 37203, United States
Vanderbilt University Medical Center
Nashville, Tennessee 37230, United States

References and documents

Publications

Simon R. Optimal two-stage designs for phase II clinical trials. Control Clin Trials. 1989 Mar;10(1):1-10. doi: 10.1016/0197-2456(89)90015-9. PubMed 2702835 ↗
Hellmann MD, Janne PA, Opyrchal M, Hafez N, Raez LE, Gabrilovich DI, Wang F, Trepel JB, Lee MJ, Yuno A, Lee S, Brouwer S, Sankoh S, Wang L, Tamang D, Schmidt EV, Meyers ML, Ramalingam SS, Shum E, Ordentlich P. Entinostat plus Pembrolizumab in Patients with Metastatic NSCLC Previously Treated with Anti-PD-(L)1 Therapy. Clin Cancer Res. 2021 Feb 15;27(4):1019-1028. doi: 10.1158/1078-0432.CCR-20-3305. Epub 2020 Nov 17. PubMed 33203644 ↗

Study documents

Study protocol · Apr 12, 2018
Statistical analysis plan · Sep 26, 2019

Documents are hosted by the registry — open the source record to download them.

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Mar 20, 2025, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT02437136
Lead sponsor: Syndax Pharmaceuticals
Collaborators: Merck Sharp & Dohme LLC
Responsible party: Sponsor
First posted: May 7, 2015
Start date: Aug 26, 2015
Primary completion: Sep 29, 2022
Completion: Sep 29, 2022
Results posted: Mar 20, 2025
Last update: Mar 20, 2025

Study contacts

Pasi A Janne, MD, PhD

principal investigator · Dana-Farber Cancer Institute

Oversight

Data monitoring committee: No

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