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

NCT04877821 | Completed Phase 2

• 1 other identifier: 2021-19
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Triple Negative Breast Cancer

Keywords

TNBC; neoadjuvant; immunotherapy; anti-angiogenesis

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• Residual cancer burden (RCB)

  Up to approximately 30-32 weeks

• Event-free Survival (EFS) as assessed by Investigator

  Up to approximately 3 years

• Overall survival (OS)

  Up to approximately 5 years

• Immune response biomarkers

  Up to approximately 60 weeks

• Percentage of participants who experience an adverse event (AE)

  Up to approximately 60 weeks

Other Outcomes (4)

• European Orgnisation for Research and Treatment of Cancer (EORTC) Quality of Life Core 30 Questionnaire (QLQ-C30) score

  Up to approximately 48-52 weeks

• EORTC Breast Cancer-Specific QoL Questionnaire (QLQ-BR42) score

  Up to approximately 48-52 weeks

• Patient Health Questionnaire-9 (PHQ-9)

  Up to approximately 48-52 weeks

Study Arms (1)

Sintilimab + Anlotinib + Chemotherapy

EXPERIMENTAL

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; Drug: Anlotinib; Drug: Nab paclitaxel; Drug: Carboplatin; Drug: Epirubicin; Drug: Cyclophosphamide

Interventions

Sintilimab DRUG

200mg on days 1 (Q3W) of the neoadjuvant and adjuvant phase of the study; IV injection.

Sintilimab + Anlotinib + Chemotherapy

Anlotinib DRUG

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.

Sintilimab + Anlotinib + Chemotherapy

Nab paclitaxel DRUG

100 mg/m² on day 1, 8 and 15 of Cycles 1-4 (Q3W) of the neoadjuvant phase of the study; IV injection.

Sintilimab + Anlotinib + Chemotherapy

Carboplatin DRUG

AUC 5 on days 1 of Cycles 1-4 (Q3W) of the neoadjuvant phase of the study; IV injection.

Sintilimab + Anlotinib + Chemotherapy

Epirubicin DRUG

90 mg/m² on day of Cycles 5-8 (Q3W) of the neoadjuvant phase of the study; IV injection.

Sintilimab + Anlotinib + Chemotherapy

Cyclophosphamide DRUG

600 mg/m² on day of Cycles 5-8 (Q3W) of the neoadjuvant phase of the study; IV injection.

Sintilimab + Anlotinib + Chemotherapy

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• Guangdong Provincial People's Hospital: lead

Study Sites (1)

NeoSACT

Guangzhou, Guangdong, 510080, China

Location

Related Publications (1)

• 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.

  PMID: 40541191 DERIVED

MeSH Terms

Conditions

Triple Negative Breast Neoplasms

Interventions

sintilimab; anlotinib; Taxes; Carboplatin; Epirubicin; Cyclophosphamide

Condition Hierarchy (Ancestors)

Breast Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Economics; Health Care Economics and Organizations; Coordination Complexes; Organic Chemicals; Doxorubicin; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Professor

Model Details: Patient enrollment followed a Simon two-stage design.The Simon design required 11 patients for the first stage and called for termination at stage 1 if there were less than 5 responders (Pathological complete response, pCR) among 11 patients. Otherwise, if seven or more responders were identified in up to 11 patients, additional 20 patients would be enrolled. Treatment was considered of clinical interest if, at the end of the second stage, there were more than 16 responders among 31 patient.

Study Record Dates

• First Submitted: April 30, 2021
• First Posted: May 7, 2021
• Study Start: September 15, 2021
• Primary Completion: August 31, 2023
• Study Completion: March 10, 2026
• Last Updated: April 2, 2026

Record last verified: 2026-03

Locations

CN (1)