Chidamide and PD-1 Inhibitor Plus Anlotinib for HER2-low Breast Cancer That Has Spread or Cannot be Surgically Removed

A Phase 2, Single Arm Study Investigating the Use of Chidamide and PD-1 Antibody Combination With Anlotinib in HER2-low, Unresectable and/or Metastatic Breast Cancer

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

Study Overview

• Status: Not yet recruiting
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: Tucidinostat (chidamide), PD-1 inhibitor (tislelizumab), anlotinib

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Tucidinostat (chidamide), PD-1 inhibitor (tislelizumab), Anlotinib	Drug: Tucidinostat (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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival(PFS)	Time from treatment until disease progression or death	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate（ORR）	Objective Response Rate（ORR）by RECIST 1.1,the total proportion of patients with complete response（CR）, partial response（PR）	2 years
Disease Control Rate （DCR）	the total proportion of patients with complete response（CR）, partial response（PR）and stable disease（SD）	2 years
Clinical Benefit Rate (CBR)	the total proportion of patients with Partial Response (PR), Complete Response (CR) or Stable Disease (SD) ≥6 months	2 years
Overall survival (OS)	Time from treatment until death from any cause	2 years

Collaborators and Investigators

• Sponsor: Guangdong Provincial People's Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): September 1, 2024
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: August 7, 2024
• First Submitted That Met QC Criteria: August 7, 2024
• First Posted (Actual): August 9, 2024

Study Record Updates

• Last Update Posted (Actual): August 9, 2024
• Last Update Submitted That Met QC Criteria: August 7, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Tislelizumab
• Other Study ID Numbers: CSIIT-C56

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No