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.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
89
An orally available histone deacetylases inhibitor (HDAC).
A humanized, engineered monoclonal antibody of IgG1 isotype against the protein programmed cell death ligand 1 (PD-L1).
A pill containing no active drug ingredient
Phase 1b: Participants Experiencing DLT
Phase 1b employed a classical 3+3 design, with the determination of DLT based on entinostat in combination with atezolizumab within the first cycle of treatment (that is, between Day 1 to Day 21 of Cycle 1). Six participants were required to be treated in a dose level for it to be considered MTD or the Recommended Phase 2 Dose (RP2D). A DLT was defined as the occurrence of specific events, defined in the protocol, that were considered by the investigator to be at least possibly related to study drug using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events version 4.03.The DLT assessment window (Cycle 1) was the time period between Cycle 1 Day 1 until Cycle 2 Day 1 (expected to be 21 days after Cycle 1 Day 1).
Time frame: Up to 21 days after Cycle 1 Day 1
Phase 1b: Determination of the RP2D
Phase 1b employed a classical 3+3 design, with the determination of the RP2D based on entinostat in combination with atezolizumab within the first cycle of treatment (that is, between Day 1 to Day 21 of Cycle 1). The RP2D was defined as equal to or less than the preliminary maximum tolerated dose (MTD) and was determined in discussion with the sponsor, the study medical monitor, and dose determination phase investigators. The MTD was defined as the highest dose level at which \<33% of 6 participants experience DLT.
Time frame: Up to 21 days after Cycle 1 Day 1
Phase 2 Expansion: Duration of Progression-free Survival (PFS) Using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
The duration of PFS, assessed using RECIST 1.1, was used to evaluate the efficacy of entinostat at the RP2D in combination with atezolizumab in participants with advanced triple negative breast cancer (aTNBC). It was defined as the number of months from randomization to the earlier of progressive disease or death due to any cause. One month was considered 30.4375 days. PFS (months) = (Date of Progression or Censoring - Date of Randomization + 1)/30.4375.
Time frame: Up to 1 year
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
UAB Comprehensive Cancer Center
Birmingham, Alabama, United States
CBCC Global Research at Comprehensive Blood and Cancer Center
Bakersfield, California, United States
St. Jude Medical Center
Fullerton, California, United States
Los Angeles Hematology Oncology Medical Group
Glendale, California, United States
Torrance Memorial Cancer Care Associates
Redondo Beach, California, United States
SLO Oncology and Hematology Health Center
San Luis Obispo, California, United States
Central Coast Medical Oncology Group
Santa Maria, California, United States
UCLA Hematology/Oncology - Santa Monica
Santa Monica, California, United States
Saint Mary's Regional Cancer Center
Grand Junction, Colorado, United States
Office of Human Research
Hollywood, Florida, United States
...and 19 more locations
Phase 2 Expansion: Duration of PFS Using Immune Response RECIST (irRECIST)
The duration of PFS, assessed using irRECIST, was used to evaluate the efficacy of entinostat at the RP2D in combination with atezolizumab in participants with aTNBC. It was defined as the number of months from randomization to the earlier of progressive disease or death due to any cause. One month was considered 30.4375 days. PFS (months) = (Date of Progression or Censoring - Date of Randomization + 1)/30.4375.
Time frame: Up to 1 year
Phase 2 Expansion: Overall Response Rate (ORR) Using RECIST 1.1 and irRECIST
ORR was defined as the crude percentage of participants achieving a best overall response of complete response (CR) or partial response (PR) assessed using RECIST 1.1 and irRECIST. ORR calculated as: (number of participants with best overall response as CR or PR)/total number of participants. The overall response was determined locally by the investigator at each scheduled assessment.
Time frame: Up to 1 year
Phase 2 Expansion: Clinical Benefit Rate (CBR) Using RECIST 1.1 and irRECIST
CBR was estimated based on the crude percentage of participants in each treatment arm whose best overall response during the course of study treatment was CR, PR, or stable disease (SD) lasting for at least 24 weeks (measured from the date of randomization to the last date where SD was reported).
Time frame: Up to 1 year
Phase 2 Expansion: Overall Survival (OS)
OS was defined as the number of months from randomization to date of death from any cause. Participants who were alive or lost to follow-up as of a data analysis cutoff date were right-censored. One month was considered 30.4375 days. OS (months) = (Date of Death/Censoring - Date of Randomization + 1)/30.4375
Time frame: Up to 5 years
Phase 2 Expansion: Duration of Response (DOR)
DOR was defined as the number of months from the date where a CR/PR (based on RECIST 1.1) or immune response CR (irCR)/immune response PR (irPR) was firstly observed, to the first date that recurrent or progressive disease was documented.
Time frame: Up to 2 years
Phase 2 Expansion: Time To Response (TTR)
TTR was defined for the subset of participants that achieved best overall response of confirmed CR/PR or confirmed irCR/irPR as the number of months from date of randomization to date of the initial documented response of CR/PR (based on RECIST 1.1) or irCR/irPR (based on irRECIST).
Time frame: Up to 2 years