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

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.

Study Overview

• Status: Completed
• Conditions: Triple Negative Breast Cancer
• Intervention / Treatment: Drug: Sintilimab; Drug: Anlotinib; Drug: Nab paclitaxel; Drug: Carboplatin; Drug: Epirubicin; Drug: Cyclophosphamide

• Study Type: Interventional
• Enrollment (Actual): 29
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510080
      • NeoSACT

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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).

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: Sintilimab + Anlotinib + Chemotherapy; Experimental: Sintilimab + Anlotinib + Chemotherapy Participants receive Sintilimab every 3 weeks (Q3W) + Anlotinib d1-14 (Q3W) + (Nab paclitaxel weekly + carboplatin (Q3W) x 4 cycles followed by epirubicin + cyclophosphamide Q3W x 4 cycles) as neoadjuvant therapy prior to surgery. After surgery, the subjects will continue to receive sintilimab treatment until one year has elapsed since the start of neoadjuvant therapy (that is, they will receive sintilimab treatment at least 17 times).

Drug: Sintilimab; 200mg on days 1 (Q3W) of the neoadjuvant and adjuvant phase of the study; IV injection.; Drug: Anlotinib; 12mg on d1-14 of Cycles 1-8 (Q3W) of the neoadjuvant phase of the study; po. Arotinib is a small molecule multi-target TKI, which exerts its effect by inhibiting angiogenesis, a critical component of tumour growth and metastasis.; Drug: Nab paclitaxel; 100 mg/m² on day 1, 8 and 15 of Cycles 1-4 (Q3W) of the neoadjuvant phase of the study; IV injection.; Drug: Carboplatin; AUC 5 on days 1 of Cycles 1-4 (Q3W) of the neoadjuvant phase of the study; IV injection.; Drug: Epirubicin; 90 mg/m² on day of Cycles 5-8 (Q3W) of the neoadjuvant phase of the study; IV injection.; Drug: Cyclophosphamide; 600 mg/m² on day of Cycles 5-8 (Q3W) of the neoadjuvant phase of the study; IV injection.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pathological complete response (pCR) rate using the definition of ypT0/Tis ypN0 (i.e., no invasive residual in breast or nodes; noninvasive breast residuals allowed) at the time of definitive surgery	pCR rate (ypT0/Tis ypN0) is defined as the percentage of participants without residual invasive cancer on hematoxylin and eosin evaluation of the complete resected breast specimen and all sampled regional lymph nodes following completion of neoadjuvant systemic therapy by current American Joint Committee on Cancer (AJCC) staging criteria assessed by the local pathologist at the time of definitive surgery.	Up to approximately 30-32 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of participants who experience an adverse event (AE)	An AE is defined as any untoward medical occurrence in a participant administered study treatment which does not necessarily have to have a causal relationship with this treatment. An AE can be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of study treatment or protocol-specified procedure, whether or not considered related to study treatment or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition that is temporally associated with the use of study treatment, is also an AE.	Up to approximately 60 weeks
Event-free Survival (EFS) as assessed by Investigator	EFS is defined as the time from randomization to any of the following events: progression of disease that precludes surgery, local or distant recurrence, second primary malignancy (breast or other cancers) or death due to any cause.	Up to approximately 3 years
Residual cancer burden (RCB)	Residual cancer burden (RCB)	Up to approximately 30-32 weeks
Overall survival (OS)	OS is defined as the time from randomization to death due to any cause.	Up to approximately 5 years
Immune response biomarkers	PDL1, CD8, Tils, HRD...	Up to approximately 60 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
European Orgnisation for Research and Treatment of Cancer (EORTC) Quality of Life Core 30 Questionnaire (QLQ-C30) score	The EORTC-QLQ-C30 is a 30-item questionnaire developed to assess the quality of life of cancer patients. Individual responses are given on a 4-point scale (1=Not at All to 4=Very Much), with a lower score indicating a better outcome.	Up to approximately 48-52 weeks
EORTC Breast Cancer-Specific QoL Questionnaire (QLQ-BR42) score	The EORTC-QLQ-BR42 is a 42-item questionnaire developed to assess the quality of life of breast cancer patients. And it is now a fully validated EORTC questionnaire and can be used in conjunction with the QLQ-C30. Individual responses are given on a 4-point scale (1=Not at All to 4=Very Much), with a lower score indicating a better outcome.	Up to approximately 48-52 weeks
Patient Health Questionnaire-9 (PHQ-9)	PHQ-9 is a nine-item questionnaire for screening depression symptoms and measuring its severity rated on a scale of 0 (not at all), 1 (several days), 2 (more than half the days) or 3(nearly every day). The severity of depressive symptoms in this study will be classified into three subgroups according to the PHQ-9 score: no depression (0-4), mild depression (5-9) and moderate-to-severe depression (≥10). The cutoff score and its severity of PHQ-9 had been extensively applied to screen symptoms of depression in studies involving patients with cancer.	Up to approximately 48-52 weeks
Generalized Anxiety Disorder 7-item (GAD-7)	GAD-7 is a seven-item questionnaire for screening anxiety symptoms and measuring its severity rated on a scale of 0 (not at all), 1 (several days), 2 (more than half the days) or 3 (nearly every day). The severity of anxiety symptoms in this study will be classified into three subgroups based on the GAD-7 scores: no anxiety (0-4), mild anxiety (5-9) and moderate-to-severe anxiety(≥10).GAD-7 had shown satisfactory validity and reliability for screening anxiety symptoms with cancer.	Up to approximately 48-52 weeks

Collaborators and Investigators

• Sponsor: Guangdong Provincial People's Hospital

Publications and helpful links

General Publications

• Zhang L, Yang L, Ge Y, Zhu Z, Chen B, Yang C, Gao H, Yang M, Zhu T, Wang K. Neoadjuvant anlotinib/sintilimab plus chemotherapy in triple-negative breast cancer (NeoSACT): Phase 2 trial. Cell Rep Med. 2025 Jul 15;6(7):102193. doi: 10.1016/j.xcrm.2025.102193. Epub 2025 Jun 19.

Study record dates

Study Major Dates

• Study Start (Actual): September 15, 2021
• Primary Completion (Actual): August 31, 2023
• Study Completion (Actual): March 10, 2026

Study Registration Dates

• First Submitted: April 30, 2021
• First Submitted That Met QC Criteria: May 6, 2021
• First Posted (Actual): May 7, 2021

Study Record Updates

• Last Update Posted (Actual): April 2, 2026
• Last Update Submitted That Met QC Criteria: March 29, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: neoadjuvant; immunotherapy; TNBC; anti-angiogenesis
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Breast Neoplasms; Skin and Connective Tissue Diseases; Triple Negative Breast Neoplasms; Organic Chemicals; Hydrocarbons; Hydrocarbons, Cyclic; Carbohydrates; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Polycyclic Compounds; Glycosides; Coordination Complexes; Health Care Economics and Organizations; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Anthracyclines; Naphthacenes; Aminoglycosides; Daunorubicin; Doxorubicin; Economics; Cyclophosphamide; Carboplatin; Epirubicin; anlotinib; sintilimab; Taxes
• Other Study ID Numbers: 2021-19

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No