Combination Therapy With Entinostat and Pembrolizumab in Relapsed and Refractory Lymphomas

Inclusion Criteria:

- Patient is ≥ 18 years of age at the time of signing Informed Consent

- Patient has histologically confirmed diagnosis of follicular lymphoma or Hodgkin
lymphoma

- Hodgkin lymphoma patients must have received at least 2 prior regimens and received,
declined, or be ineligible for autologous transplant

- Follicular lymphoma patients must have received at least 3 prior lines of therapy;
patients are eligible regardless of whether they have received an autologous
transplant.

- Prior HDAC inhibitor and/or anti-PD1, anti-PDL1, anti-PD-L2, anti-CD137 or
anti-cytotoxic T- lymphocyte associated antigen 4 (CTLA-4) antibody allowed as long
patient received clinical benefit from it, best response was not progressive disease
and it was not the most recent treatment

- Patients who have undergone an allogeneic HSCT within the last 5 yrs are eligible for
enrollment if they have no signs or symptoms of active GvHD and are off all immune
suppressive medications.

- Patient has at least one measurable nodal lesion (≥ 2.0 cm)

- Patient has an Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1

- Patient has adequate bone marrow and organ function by:

- Absolute neutrophil count (ANC) ≥ 1.0 x 10^9/L

- Platelets ≥75 x 10^9/L

- Hemoglobin (Hgb) ≥ 9.0 g/dL

- Serum Creatinine ≤ 1.5 x upper limit of normal (ULN)

- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 1.5 x ULN
(or

≤3 x ULN if liver involved with disease

- Total serum bilirubin ≤ 1.5 x ULN ( ≤ 3 x ULN with direct bilirubin within normal
range in patients with documented hepatic involvement, well documented Gilbert‟s
Syndrome)

- International Normalized Ratio (INR) or Prothrombin

- Time (PT) ≤1.5×ULN unless patient is receiving anticoagulant therapy as long as
PT or PTT is within therapeutic range of intended use of anticoagulants

- Activated Partial Thromboplastin Time (aPTT) ≤1.5×ULN unless patient is receiving
anticoagulant therapy as long as PT or PTT is within therapeutic range of
intended use of anticoagulants

- Female subject of childbearing potential should have a negative urine or serum
pregnancy within 72 hours prior to receiving the first dose of study medication. If
the urine test is positive or cannot be confirmed as negative, a serum pregnancy test
will be required.

- Female subjects of childbearing potential must be willing to use an adequate method of
contraception as outlined in Contraception, for the course of the study through 120
days after the last dose of study medication. Note: Abstinence is acceptable if this
is the usual lifestyle and preferred contraception for the subject.

- Male subjects of childbearing potential (Section 9.8.2) must agree to use an adequate
method of contraception as outlined in Section 9.8.2- Contraception, starting with the
first dose of study therapy through 120 days after the last dose of study therapy.

Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception
for the subject.

Exclusion Criteria:

- Diagnosed or treated for malignancy other than the indication under study except for

- Malignancy treated with curative intent and with no known active disease present
for

≥ 3 years before the first dose of study treatment

- Adequately treated non-melanoma skin cancer or lentigo maligna without evidence
of disease

- Adequately treated cervical carcinoma in situ without evidence of disease

- History of Human Immunodeficiency Virus (HIV)

- Active Hepatitis B or C infection

- History of active TB (Bacillus Tuberculosis)

- Concurrent enrollment in another therapeutic investigational clinical study or has
participated in a study of an investigational agent and received study therapy or used
a n investigational device within 4 weeks of the first dose of study drug

- Prior anti-tumor therapy within 2 weeks

- Known CNS lymphoma involvement

- Any uncontrolled active systemic infection or any life-threatening illness, medical
condition, or organ system dysfunction which, in the investigator‟s opinion, could
compromise the subject‟s safety, interfere with the absorption or metabolism of
entinostat capsules, or put the study outcomes at undue risk.

- Any history of (non-infectious) pneumonitis that required steroids, evidence of
interstitial lung disease or active, non- infectious pneumonitis

- 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 msec.

- History of Torsades de pointes, ventricular tachycardia, or ventricular fibrillation

- Uncontrolled heart failure or hypertension or uncontrolled diabetes mellitus

- Any active autoimmune disease or a documented history of autoimmune disease
(excluded/exception to the rule: subjects with vitiligo or resolved childhood
asthma/atopy, type I diabetes mellitus, subjects with hypothyroidisms stable on
hormone replacement, Sjorgen‟s syndrome, psoriasis not requiring systemic treatment,
or conditions not expected to recur in the absence of an external trigger).

- Any syndrome that requires systemic treatment with either corticosteroids (> 10 mg
daily prednisone equivalents) or other immunosuppressive medications within 7 days of
study drug administration. Of note: Inhaled or topical steroids, and adrenal
replacement doses > 10 mg daily prednisone equivalents, are permitted in the absence
of active autoimmune disease.

- A woman who is pregnant or breast feeding

- Has received a live vaccine within 30 days of planned start of study therapy. Note:
Seasonal influenza vaccines for injection are generally inactivated flu vaccines and
are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live
attenuated vaccines, and are not allowed

- 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, 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

- Allergy to benzamide or inactive components of entinostat