SNDX-275-0602 is a Phase 1b/2 study evaluating the combination of entinostat plus
atezolizumab in patients with aTNBC. The study has 2 phases: an open-label Dose Determination
Phase (Phase 1b) followed by an Expansion Phase (Phase 2). The Expansion Phase will evaluate
the efficacy and safety of entinostat when administered at the RP2D with atezolizumab in
patients with aTNBC in a randomized, double-blind, placebo-controlled setting. Up to 88
evaluable patients are anticipated if the study completes all phases of evaluation (up to 18
patients for Phase 1b, up to 70 patients for Phase 2). Up to 30 study centers in the US and
Europe may participate.
Safety will be assessed during the study by documentation of AEs, clinical laboratory tests,
physical examinations, vital sign measurements, electrocardiograms (ECGs), and Eastern
Cooperative Oncology Group (ECOG) performance status. Adverse events of special interest
(AESI) will be collected and reviewed in a manner consistent with serious adverse event
reporting procedures.
Inclusion Criteria:
1. Has histologically or cytologically confirmed triple negative breast carcinoma that is
either metastatic (stage IV of the TNM classification) or locally recurrent and not
amenable to local curative treatment.
2. Evidence of measurable, locally recurrent or metastatic disease based on imaging
studies within 28 days before the first dose of study drug.
3. Has received at least 1, but no more than 2, prior lines of systemic therapy for
locally recurrent and/or metastatic disease.
4. If patient has a history of treated asymptomatic CNS metastases they are eligible,
provided they meet all of the following criteria: Patient has measurable disease
outside CNS; Patient does not have metastases to midbrain, pons, medulla or spinal
cord; Patient is not on corticosteroids as therapy for CNS disease (anticonvulsants at
a stable dose are allowed); Patient has not had whole-brain radiation within 6 weeks
prior to study enrollment; Patient has stable CNS disease as demonstrated by at least
4 weeks of stability between the last intervention scan and the study screening scan
5. ECOG performance status of 0 or 1.
6. Has acceptable, applicable laboratory parameters.
7. Female subjects must not be pregnant; willing to use 2 methods of birth
control/abstinence if applicable through 120 days after the last dose of study drug
8. Experienced resolution of toxic effect(s) of the most recent prior anti-cancer therapy
to Grade <1 (except alopecia or neuropathy).
9. Able to understand and give written informed consent and comply with study procedures.
Exclusion Criteria:
1. Diagnosis of immunodeficiency or receiving systemic steroid therapy or any other form
of immunosuppressive therapy within 7 days prior to the first dose of study drug.
2. Active autoimmune disease including active diverticulitis, symptomatic peptic ulcer
disease, colitis, or inflammatory bowel disease that has required systemic treatment
in past 2 years
3. Previously treated with a PD-1/PD-L1-blocking antibody or a histone deacetylase
inhibitor
4. History or current evidence of any condition, therapy, or laboratory abnormality that
might confound the results of the study, interfere with the patient'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: History of immune deficiencies or autoimmune disease; Myocardial infarction or
arterial thromboembolic events within 6 months prior to screening or severe or
unstable angina, New York Heart Association (NYHA) Class III or IV disease, or a QTc
interval > 470 msec; Uncontrolled hypertension or diabetes mellitus; Another known
malignancy that is progressing or requires active treatment; Active infection
requiring systemic therapy; Known active central nervous system (CNS) metastases
and/or carcinomatous meningitis.
5. Any contraindication to oral agents or significant nausea and vomiting, malabsorption,
or significant small bowel resection that, in the opinion of the investigator, would
preclude adequate absorption.
6. Received a live vaccine within 30 days of the first dose of treatment.
7. Prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to enrollment or who
has not recovered from AEs due to mAb agents administered more than 4 weeks earlier.
8. Prior chemotherapy within 3 weeks, targeted small molecule therapy or radiation
therapy within 2 weeks prior to enrollment, or who has not recovered (i.e., ≤Grade 1
at enrollment) from AEs due to a previously administered agent.
9. Received transfusion of blood products or administration of colony stimulating factors
within 4 weeks prior to the first dose of treatment.
10. 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 study drug.
11. Currently receiving treatment with any other agent listed on the prohibited medication
list
12. If female, is pregnant, breastfeeding, or expecting to conceive starting with the
screening visit through 120 days after the last dose of study drug.
13. Known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies).
14. Known active hepatitis B or hepatitis C
15. Allergy to benzamide or inactive components of entinostat.
16. History of allergies to any active or inactive ingredients of atezolizumab.
17. Known psychiatric or substance abuse disorders that would interfere with cooperation
with the requirements of the study.
