A Prospective, Open, Single-arm, Phase Ⅱ Clinical Study of Anlotinib Combined With Tislelizumab and AT in the Neoadjuvant Treatment of Triple-negative Breast Cancer
Overview
- Phase
- Phase 2
- Intervention
- AT regimen
- Conditions
- Triple-negative Breast Cancer
- Sponsor
- Sichuan Provincial People's Hospital
- Enrollment
- 32
- Locations
- 1
- Primary Endpoint
- 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
- Status
- Recruiting
- Last Updated
- 2 years ago
Overview
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.
Investigators
Luojing
Prof.
Sichuan Provincial People's Hospital
Eligibility Criteria
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.
- •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:
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.
- •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;
Arms & Interventions
Tislelizumab + Anlotinib + Chemotherapy
Participants receive Tislelizumab every 3 weeks (Q3W) + Anlotinib d1-14 (Q3W) + AT regimen (Q3W) x 6 cycles as neoadjuvant therapy prior to surgery.
Intervention: AT regimen
Tislelizumab + Anlotinib + Chemotherapy
Participants receive Tislelizumab every 3 weeks (Q3W) + Anlotinib d1-14 (Q3W) + AT regimen (Q3W) x 6 cycles as neoadjuvant therapy prior to surgery.
Intervention: Tislelizumab
Tislelizumab + Anlotinib + Chemotherapy
Participants receive Tislelizumab every 3 weeks (Q3W) + Anlotinib d1-14 (Q3W) + AT regimen (Q3W) x 6 cycles as neoadjuvant therapy prior to surgery.
Intervention: Anlotinib
Outcomes
Primary Outcomes
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
Time Frame: up to approximately 21-24 weeks
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.
Secondary Outcomes
- invasive disease-free survival(IDFS)(up to approximately 3 years)
- Overall survival (OS)(up to approximately 5 years)
- Percentage of participants who experience an adverse event (AE)(up to approximately 60 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)
- 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)