The Efficacy and Safety of Sintilimab Plus Anlotinib Combined With Chemotherapy as Neoadjuvant Therapy in TNBC

An Open-label Phase II Trial Evaluating the Efficacy and Safety of Sintilimab Plus Anlotinib Combined With Chemotherapy as Neoadjuvant Therapy in Early-stage Triple-negative Breast Cancer（NeoSACT）

The purpose of this study is to evaluate the efficacy and safety of Sintilimab plus anlotinib combined with chemotherapy as neoadjuvant therapy in participants who have triple negative breast cancer (TNBC). After a screening phase of approximately 28 days, each participant will receive neoadjuvant study treatment (Sintilimab + anlotinib + chemotherapy) based on schedule for approximately 24 weeks (8 cycles). Each participant will then undergo definitive surgery 4-6 weeks after conclusion of the last cycle of the neoadjuvant study treatment. Following adjuvant study treatment, each participant will be monitored for safety, survival and disease recurrence. The primary outcome measure is pathological complete response (pCR) rate using the definition of ypT0/Tis ypN0.

Inclusion Criteria:

• Has newly diagnosed, locally advanced TNBC, as defined by the most recent American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines.
• Has previously untreated locally advanced non-metastatic (M0) TNBC defined as the following combined primary tumor (T) and regional lymph node (N) staging per current American Joint Committee of Cancer (AJCC) staging criteria for breast cancer as assessed by the investigator based on radiological and/or clinical assessment:

T1c, N1-N2 T2, N0-N2 T3, N0-N2 T4a-d, N0-N2

• Provides a core needle biopsy consisting of at least 2 separate tumor cores from the primary tumor at screening to the central laboratory.
• Has Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 performed within 10 days of treatment initiation.
• Demonstrates adequate organ function.
• Female participants of childbearing potential must be willing to use an adequate method of contraception for the course of the study through 12 months after the last dose of study treatment for participants who have received cyclophosphamide, and 6 months after the last dose of study treatment for participants who did not.

Exclusion Criteria:

• Has a history of invasive malignancy ≤5 years prior to signing informed consent except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer.
• Has received prior chemotherapy, targeted therapy, and radiation therapy within the past 12 months.
• Has received prior therapy with an anti-programmed cell death protein 1 (anti-PD-1), anti-programmed death - ligand 1 (anti-PD-L1), or antiangiogenic drug therapy.
• Is currently participating in or has participated in an interventional clinical study with an investigational compound or device within 4 weeks of the first dose of treatment in this current study.
• Has received a live vaccine within 30 days of the first dose of study treatment.
• Has an active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs).
• Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy (i.e., dosing exceeding 10 mg daily of prednisone or equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study treatment.
• Has a known history of Human Immunodeficiency Virus (HIV).
• Has known active Hepatitis B or Hepatitis C.
• Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis.
• Has an active infection requiring systemic therapy.
• Has significant cardiovascular disease, such as: history of myocardial infarction, acute coronary syndrome or coronary angioplasty/stenting/bypass grafting within the last 6 months OR congestive heart failure (CHF) New York Heart Association (NYHA) Class II-IV or history of CHF NYHA Class III or IV.
• Is pregnant or breastfeeding, or expecting to conceive children within the projected duration of the study, starting with the screening visit through 12 months after the last dose of study treatment for participants who have received cyclophosphamide, and for 6 months after the last dose of study treatment for participants who have not.
• Has a known hypersensitivity to the components of the study treatment or its analogs.
• Has a known history of active tuberculosis (TB, Bacillus Tuberculosis).