A Phase Ⅱ Study of Anlotinib Combined With Tislelizumab and AT in the Neoadjuvant Treatment of Triple-negative Breast Cancer

NCT04914390 | Unknown Phase 2

• 1 other identifier: ALTERBC008
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief Summary

This is a prospective, single-arm and open-label phase II study, evaluating the efficacy and safety of anlotinib combined with tislelizumab and AT regimen as neoadjuvant treatment for triple-negative breast cancer. Participants will undergo/receive PDL1 testing after enrollment. All patients will be receive 6 cycles of low-dose anlotinib combined with tislelizumab and AT（Doxorubicin or Epirubicin+albumin-bound paclitaxel）regimen, followed by surgery.

Conditions

Triple-negative Breast Cancer

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 21-24 weeks

Secondary Outcomes (6)

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

  Up to approximately 3 years

• pCR rate using an alternative definition, ypT0 ypN0 (i.e., no invasive or noninvasive residual in breast or nodes) at the time of definitive surgery

  up to approximately 21-24 weeks

• pCR rate using an alternative definition, ypT0/Tis (i.e., absence of invasive cancer in the breast irrespective of ductal carcinoma in situ or nodal involvement) at the time of definitive surgery

  up to approximately 21-24 weeks

• invasive disease-free survival(IDFS)

  up to approximately 3 years

• Overall survival (OS)

  up to approximately 5 years

Study Arms (1)

Tislelizumab + Anlotinib + Chemotherapy

EXPERIMENTAL

Participants receive Tislelizumab every 3 weeks (Q3W) + Anlotinib d1-14 (Q3W) + AT regimen (Q3W) x 6 cycles as neoadjuvant therapy prior to surgery.

Drug: AT regimen; Drug: Tislelizumab; Drug: Anlotinib

Interventions

AT regimen DRUG

Doxorubin 60mg/㎡ d1 or Epirubicin 75mg/㎡ d1 and Nab-paclitaxel 260mg/㎡ d1 of Cycles 1-6 (Q3W) of the neoadjuvant phase of the study; IV injection.

Also known as: Anthracycline/Nab-paclitaxel

Tislelizumab + Anlotinib + Chemotherapy

Tislelizumab DRUG

200mg on d1 of Cycles 1-6 (Q3W) of the neoadjuvant phase of the study; IV injection.

Also known as: BGB-A317

Tislelizumab + Anlotinib + Chemotherapy

Anlotinib DRUG

8mg on d1-14 of Cycles 1-5 (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.

Also known as: AL3818

Tislelizumab + Anlotinib + Chemotherapy

Eligibility Criteria

• Age: 18 Years - 75 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.
• Age 18-75 years, female patients
• ECOG performance status ≤1
• 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
• Demonstrates adequate organ function:
• Patients did not receive blood, platelet transfusion or growth factor support treatment within 14 days before blood sample collection in the screening period, and needed to meet:
• Hemoglobin（HB）\>= 9g / dL;
• The absolute value of neutrophil（ANC）\>= 1.5 x 10\^9/L;
• Platelets（PLT）\>= 100 x 10\^9/L;
• The biochemical inspection must meet the following indicators:
• Serum creatinine（Cr）\<= 1.5 ULN, or creatinine clearance（CCr）\>= 60mL / min;
• Total bilirubin（TBIL）\<= 1.5 ULN, Or total bilirubin\>1.0 ULN but direct bilirubin \<= 1.0 ULN;
• AST and ALT \<= 2.5 ULN.
• Female participants of childbearing potential must be willing to use an adequate method of contraception for the course of the study through \>= 120 days after the last dose of study treatment, and have a negative serum pregnancy test \<= 7 days before the first administration of the study drug.

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.
• Patients who are known to be allergic to Tislelizumab, Anlotinib, nab-paclitaxel or Anthracyclines;
• Has multiple factors affecting oral medication. Such as inability to swallow, chronic diarrhea and intestinal obstruction;
• Patients with any severe and/or uncontrolled disease, including:
• Patients whose blood pressure control is not ideal (systolic pressure \>= 150 mmHg, diastolic pressure \>= 100 mmHg);
• Having grade I or above myocardial ischemia or infarction, arrhythmia (including QTc \>= 450ms(male) or QTc \>= 470ms(female) and grade \>= 2 congestive heart failure (New York Heart Association (NYHA) classification);
• Active or uncontrolled severe infection;
• Antiviral treatment for cirrhosis, decompensated liver disease, active hepatitis or chronic hepatitis;
• Renal failure requires hemodialysis or peritoneal dialysis;
• A history of immunodeficiency, including HIV positive or other acquired or congenital immunodeficiency diseases, or a History of organ transplantation;
• Poor control of diabetes mellitus (FBG) \> 10mmol/L;
• Urine routine indicated urinary protein \>= ++, and confirmed 24-hour quantitative urinary protein \> 1.0g;
• Patients with epileptic seizures requiring treatment;

Sponsors & Collaborators

• Sichuan Provincial People's Hospital: lead

Study Sites (1)

Department of breast surgery, Sichuan Provincial People's Hospital

Chengdu, Sichuan, 610031, China

RECRUITING

MeSH Terms

Conditions

Triple Negative Breast Neoplasms

Interventions

tislelizumab; anlotinib

Condition Hierarchy (Ancestors)

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

Study Officials

• Jing Luo, Prof.

  Sichuan Provincial People's Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jing Luo, Prof.

CONTACT

86-18981838521; luckyluojingyu@163.com

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: Prof.

Study Record Dates

• First Submitted: May 31, 2021
• First Posted: June 4, 2021
• Study Start: September 15, 2023
• Primary Completion: March 31, 2025
• Study Completion: September 30, 2025
• Last Updated: January 22, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)