Breast Cancer
Conditions
Brief summary
This Phase II study was designed to assess the efficacy and safety of the combination of PD-1 inhibitor, Tucidinostat (chidamide), a histone deacetylase inhibitor, and anlotinib in advanced breast cancer. Participants must have HER2-low and PD-L1 positive （CPS≥1）breast cancer that has been treated before. Participants' cancer: Cannot be removed by an operation Has spread to other parts of the body
Interventions
DRUGTucidinostat (chidamide), PD-1 inhibitor (tislelizumab), anlotinib
Tucidinostat (chidamide)，30mg, po., biw PD-1 inhibitor (tislelizumab), 200mg, ivgtt. d1, q3w anlotinib, 12mg, po., d1-14, q3w
Sponsors
Guangdong Provincial People's Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Has pathologically documented breast cancer that: * Is unresectable or metastatic * Has low-HER2 expression defined as IHC 2+/ISH- or IHC 1+ (ISH- or untested) * Is HR-positive * Has progressed on, and would no longer benefit from, endocrine therapy * Has been treated with 0 to 1 prior lines of chemotherapy in the recurrent or metastatic setting * Was never previously HER2-positive (ICH 3+ or ISH+) on prior pathology testing (per American Society of Clinical Oncology-College of American Pathologists \[ASCO-CAP\] guidelines) * PD-L1 positive （CPS≥1） 2. Has documented radiologic progression (during or after most recent treatment) 3. Has adequate archival tumor samples available or is wiling to provide fresh biopsies prior to randomization for: * assessment of HER2 status * assessment of post-treatment status 4. Has at least 1 measurable lesion per Response Evaluation Criteria In Solid Tumors 1.1 5. Has protocol-defined adequate cardiac, bone marrow, renal, hepatic and blood clotting functions 6. Male and female participants of reproductive/childbearing potential, agrees to follow instructions for method(s) of contraception and agrees to avoid preserving ova or sperm for at least 4.5 months after treatment (or longer, per locally approved labels)
Exclusion criteria
1. Allergies to any monoclonal antibody or tucidinostat preparation have been known, and hypersensitivity reactions of more than 3 levels have occurred 2. Previously received histone deacetylase inhibitors,or immune checkpoint inhibitor, or angiogenesis inhibitors. 3. Subjects with any active, known or suspected autoimmune disease or history of autoimmune disease. 4. Known active CNS metastases and/or carcinomatous meningitis. 5. Received a live vaccine within 4 weeks of the first dose of study medication. 6. Major surgery received or severe traumatic injury, fracture, or ulcer occurred within 4 weeks of the first dose of study medication. 7. Pregnant or lactating female. 8. Uncontrolled clinically significant systemic diseases, including active infection, unstable angina, angina occurred within 3 months,≥ NYHA II congestive heart failure, myocardial infarction occurred within 6 months, severe arrhythmia, liver, kidney, or metabolic disease. 9. Participate in other clinical trials currently or within 4 weeks prior to enrollment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free survival(PFS) | 2 years | Time from treatment until disease progression or death |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate（ORR） | 2 years | Objective Response Rate（ORR）by RECIST 1.1,the total proportion of patients with complete response（CR）, partial response（PR） |
| Clinical Benefit Rate (CBR) | 2 years | the total proportion of patients with Partial Response (PR), Complete Response (CR) or Stable Disease (SD) ≥6 months |
| Disease Control Rate （DCR） | 2 years | the total proportion of patients with complete response（CR）, partial response（PR）and stable disease（SD） |
| Overall survival (OS) | 2 years | Time from treatment until death from any cause |
Outcome results
None listed