Randomized Phase 2 Study of Atezolizumab and Entinostat in Patients With aTN Breast Cancer With Phase 1b Lead In

• Sponsor: Syndax Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02708680
• Collaborator: Roche Pharma AG (Industry)
• Enrollment: 81
• Locations: 29
• Arms: 2
• Actual Duration (Months): 58.3
• Patients Per Site: 2.8
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

The purpose of this study is to determine the safety and tolerability of entinostat used in combination with atezolizumab in patients 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 patients with aTNBC.

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer	Drug: entinostat; Drug: atezolizumab; Drug: Placebo	Phase 1/Phase 2

Detailed Description

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 81 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: May 1, 2016
• Actual Primary Completion Date: Mar 10, 2021
• Actual Study Completion Date: Mar 10, 2021

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Entinostat plus Atezolizumab Patients in this arm will receive entinostat at the RP2D in combination with atezolizumab	Drug: entinostat; An orally available histone deacetylases inhibitor (HDAC); Other Names: SNDX-275 MS-275 ; Drug: atezolizumab; A humanized, engineered monoclonal antibody of IgG1 isotype against the protein programmed cell death ligand 1 (PD-L1).; Other Names: MPDL3280A
Placebo Comparator: Placebo plus Atezolizumab Patients in this arm will receive placebo in combination with atezolizumab	Drug: atezolizumab; A humanized, engineered monoclonal antibody of IgG1 isotype against the protein programmed cell death ligand 1 (PD-L1).; Other Names: MPDL3280A ; Drug: Placebo; A pill containing no active drug ingredient

Outcome Measures

Primary Outcome Measures

1. Determination of DLT and the MTD and/or RP2D [In approximately 3 months]

   Phase 1 Dose Determination - Up to 18 patients will be enrolled in this phase of the study which employs a classical 3+3 design, with the determination of DLT and the MTD and/or RP2D based on entinostat in combination with atezolizumab in C1

2. Duration of Progression-free survival using RECIST 1.1 [In approximately 1 year]

   To perform an evaluation of the efficacy of entinostat at the RP2D in combination with atezolizumab in patients with aTNBC, as determined by the duration of progression-free survival (PFS).

Secondary Outcome Measures

1. Progression-free survival based on immune response RECIST (irRECIST) [In approximately 1 year]

   PFS status in each patient. PFS is defined as the number of months from the date of the first dose of study drug to the earliest of documented PD or death due to any cause without prior progression.

2. Overall response rate (ORR) based on RECIST 1.1 and irRECIST [In approximately 1 year]

   ORR is Complete Response + Partial Response; based on RECIST 1.1 and irRECIST

3. Clinical benefit rate (CBR) based on RECIST 1.1 and irRECIST [In approximately 1 year]

   CBR is Complete Response + Partial Response + Stable Disease for at least 24 weeks; based on RECIST 1.1 and irRECIST

4. Overall survival (OS) [In approximately 2 years]

   OS status in each patient. OS is defined as the number of months from the first dose of study drug to the date of death due to any cause.

5. Duration of response (DOR) [In approximately 2 years]

   In patients with best overall response of CR or PR; number of months from the start date of the response (and subsequently confirmed) to the first date that recurrent disease or PD is documented.

6. Time to response (TTR) [In approximately 2 years]

   In patients with best overall response of CR or PR

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	UAB Comprehensive Cancer Center	Birmingham	Alabama	United States	35201
2	CBCC Global Research at Comprehensive Blood and Cancer Center	Bakersfield	California	United States	93309
3	St. Jude Medical Center	Fullerton	California	United States	92835
4	Los Angeles Hematology Oncology Medical Group	Glendale	California	United States	91204
5	Torrance Memorial Cancer Care Associates	Redondo Beach	California	United States	90277
6	SLO Oncology and Hematology Health Center	San Luis Obispo	California	United States	93401
7	Central Coast Medical Oncology Group	Santa Maria	California	United States	93454
8	UCLA Hematology/Oncology - Santa Monica	Santa Monica	California	United States	90404
9	Saint Mary's Regional Cancer Center	Grand Junction	Colorado	United States	81501
10	Office of Human Research	Hollywood	Florida	United States	33020
11	Orlando Health, Inc.	Orlando	Florida	United States	32806
12	Ft. Wayne Hematology and Oncology	Fort Wayne	Indiana	United States	46804
13	Ft. Wayne Medical Oncology & Hematology, Inc	Fort Wayne	Indiana	United States	46845
14	Cancer Center of Kansas	Wichita	Kansas	United States	67214
15	Frauenshuh Cancer Center at Park Nicollet Health Service	Saint Louis Park	Minnesota	United States	55426
16	Saint Barnabas Medical Cancer Center	Livingston	New Jersey	United States	07039
17	Hope Women's Cancer Centers	Asheville	North Carolina	United States	28806
18	Wake Forest Baptist Medical Center	Winston-Salem	North Carolina	United States	27157
19	Texas Oncology-Baylor Charles A. Sammons Cancer Center	Dallas	Texas	United States	75201
20	Cancer Center of Adjara Autonomous Republic	Batumi	Adjara	Georgia	6010
21	Saint Nikolozi Surgery and Oncological Centre	Kutaisi	Imereti	Georgia	4600
22	Unimed Adjara - Oncology Center	Kutaisi	Imereti	Georgia	4600
23	Health House	Tbilisi		Georgia	0144
24	Institute of Clinical Oncology	Tbilisi		Georgia	0159
25	New Vision University Hospital	Tbilisi		Georgia	0159
26	Cancer Research Center	Tbilisi		Georgia	0177
27	S. Khechinashvili, University Hospital	Tbilisi		Georgia	0179
28	Multiprofile Clinic Consilium Medulla	Tbilisi		Georgia	0186
29	Research Institute of Clinical Medicine	Tbilisi		Georgia	4600

Sponsors and Collaborators

• Syndax Pharmaceuticals
• Roche Pharma AG

Investigators

• Principal Investigator: Dennis Slamon, MD, University of California, Los Angeles

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Syndax Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT02708680
• Other Study ID Numbers: SNDX-275-0602
• First Posted: Mar 15, 2016
• Last Update Posted: May 16, 2022
• Last Verified: May 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Additional relevant MeSH terms: Breast Neoplasms; Atezolizumab; Entinostat

Study Results

No Results Posted as of May 16, 2022