Clinical trial NCT02708680: Randomized Phase 2 Study of Atezolizumab and Entinostat in Patients With aTN Breast Cancer With Phase 1b Lead In
Official title: A Randomized, Placebo-controlled, Double-blind, Multicenter Phase 2 Study of Atezolizumab With or Without Entinostat in Patients With Advanced Triple Negative Breast Cancer, With a Phase 1b Lead in Phase
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Breast Cancer
Lead sponsor: Syndax Pharmaceuticals
Sponsor class: INDUSTRY
Collaborators: name: Roche Pharma AG
First posted: 2016-03-15
Enrollment: 89
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine the safety and tolerability of entinostat used in combination with atezolizumab in participants with Advanced Triple Negative Breast Cancer (aTNBC). Additionally, the purpose of the study is to assess how effective entinostat and atezolizumab are in combination in participants with aTNBC.

Detailed description: SNDX-275-0602 is a Phase 1b/2 study evaluating the combination of entinostat plus atezolizumab in participants 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 participants with aTNBC in a randomized, double-blind, placebo-controlled setting.

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.

Eligibility criteria: 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 participant has a history of treated asymptomatic CNS metastases they are eligible, provided they meet all of the following criteria: participant has measurable disease outside CNS; participant does not have metastases to midbrain, pons, medulla or spinal cord; participant is not on corticosteroids as therapy for CNS disease (anticonvulsants at a stable dose are allowed); participant has not had whole-brain radiation within 6 weeks prior to study enrollment; participant 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 participants 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 participant's participation for the full duration of the study, or is not in the best interest of the participant 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.

Primary outcomes:
measure: Phase 1b: Participants Experiencing DLT
timeFrame: Up to 21 days after Cycle 1 Day 1
measure: Phase 1b: Determination of the RP2D
timeFrame: Up to 21 days after Cycle 1 Day 1
measure: Phase 2 Expansion: Duration of Progression-free Survival (PFS) Using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
timeFrame: Up to 1 year
Secondary outcomes:
measure: Phase 2 Expansion: Duration of PFS Using Immune Response RECIST (irRECIST)
timeFrame: Up to 1 year
measure: Phase 2 Expansion: Overall Response Rate (ORR) Using RECIST 1.1 and irRECIST
timeFrame: Up to 1 year
measure: Phase 2 Expansion: Clinical Benefit Rate (CBR) Using RECIST 1.1 and irRECIST
timeFrame: Up to 1 year
measure: Phase 2 Expansion: Overall Survival (OS)
timeFrame: Up to 5 years
measure: Phase 2 Expansion: Duration of Response (DOR)
timeFrame: Up to 2 years
measure: Phase 2 Expansion: Time To Response (TTR)
timeFrame: Up to 2 years
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: UAB Comprehensive Cancer Center
state: Alabama
city: Bakersfield
country: United States
facility: CBCC Global Research at Comprehensive Blood and Cancer Center
state: California
city: Fullerton
country: United States
facility: St. Jude Medical Center
state: California
city: Glendale
country: United States
facility: Los Angeles Hematology Oncology Medical Group
state: California
city: Redondo Beach
country: United States
facility: Torrance Memorial Cancer Care Associates
state: California
city: San Luis Obispo
country: United States
facility: SLO Oncology and Hematology Health Center
state: California
city: Santa Maria
country: United States
facility: Central Coast Medical Oncology Group
state: California
city: Santa Monica
country: United States
facility: UCLA Hematology/Oncology - Santa Monica
state: California
city: Grand Junction
country: United States
facility: Saint Mary's Regional Cancer Center
state: Colorado
city: Hollywood
country: United States
facility: Office of Human Research
state: Florida
city: Orlando
country: United States
facility: Orlando Health, Inc.
state: Florida
city: Fort Wayne
country: United States
facility: Ft. Wayne Hematology and Oncology
state: Indiana
city: Fort Wayne
country: United States
facility: Ft. Wayne Medical Oncology & Hematology, Inc
state: Indiana
city: Wichita
country: United States
facility: Cancer Center of Kansas
state: Kansas
city: Saint Louis Park
country: United States
facility: Frauenshuh Cancer Center at Park Nicollet Health Service
state: Minnesota
city: Livingston
country: United States
facility: Saint Barnabas Medical Cancer Center
state: New Jersey
city: Asheville
country: United States
facility: Hope Women's Cancer Centers
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest Baptist Medical Center
state: North Carolina
city: Dallas
country: United States
facility: Texas Oncology-Baylor Charles A. Sammons Cancer Center
state: Texas
city: Batumi
country: Georgia
facility: Cancer Center of Adjara Autonomous Republic
state: Adjara
city: Kutaisi
country: Georgia
facility: Saint Nikolozi Surgery and Oncological Centre
state: Imereti
city: Kutaisi
country: Georgia
facility: Unimed Adjara - Oncology Center
state: Imereti
city: Tbilisi
country: Georgia
facility: Health House
city: Tbilisi
country: Georgia
facility: Institute of Clinical Oncology
city: Tbilisi
country: Georgia
facility: New Vision University Hospital
city: Tbilisi
country: Georgia
facility: Cancer Research Center
city: Tbilisi
country: Georgia
facility: S. Khechinashvili, University Hospital
city: Tbilisi
country: Georgia
facility: Multiprofile Clinic Consilium Medulla
city: Tbilisi
country: Georgia
facility: Research Institute of Clinical Medicine
Study officials:
affiliation: University of California, Los Angeles
name: Dennis Slamon, MD
role: PRINCIPAL_INVESTIGATOR
References: