AK105 Plus Anlotinib Hydrochloride Combined With Albumin Paclitaxel as a First-line Therapy in Patients With Advanced Triple-negative Breast Cancer

Study Overview
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Brief Summary
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This trial used a multicentre, single-arm design in which patients were treated with AK105 plus Anlotinib Hydrochloride combined with albumin paclitaxel. Patients included in this trial were advanced breast cancer with hormone receptor negative and Her2 negative. The primary endpoint is ORR, and the secondary endpoint is DCR, PFS, OS and safety.

Official Title
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AK105 Plus Anlotinib Hydrochloride Combined With Albumin Paclitaxel as a First-line Therapy in Patients With Advanced Triple-negative Breast Cancer

Conditions
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Breast Neoplasm Female

Intervention / Treatment
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* Drug: AK105
* Drug: Anlotinib hydrochloride
* Drug: Albumin Paclitaxel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Female aged 18-75 years old. ECOG 0 or 1 point. Advanced triple-negative invasive breast cancer : The pathological classification is triple negative, specifically: ER negative: IHC<1%. PR negative: IHC<1%. HER2 negative: IHC-/+ or IHC++ but FISH/CISH is negative. Tumor staging: locally advanced or recurrent/metastatic breast cancer. If the last chemotherapy drug in the previous adjuvant/neoadjuvant treatment stage is paclitaxel, paclitaxel liposome, paclitaxel albumin or docetaxel, it will take ≥6 months from the end of treatment to enrollment. At least one objectively measurable lesion according to the RECIST 1.1 . The main organs are functioning well, and the blood test results within 14 days before enrollment should meet the following requirements: Routine blood test: Hemoglobin (HB) ≥90 g/L. Neutrophil count (ANC) ≥1.5×109/L. Platelet count (PLT) ≥100×109/L. Biochemical test: Total bilirubin≤1.5×ULN (upper limit of normal). Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5×ULN; if there is liver metastasis, ALT and AST ≤ 5×ULN. Serum creatinine (Cr) ≤1.5 ULN or creatinine clearance ≥60mL/min. Must not be regnant. Volunteer to participate in this study and sign an informed consent form. Exclusion Criteria: Pregnant, lactating or planning to become pregnant during the study period. Allergic to any of the drugs in the study. Previously received PD-1/PD-L1 antibody, CTLA-4 antibody, or anti-vascular targeted therapy. Central nervous system (CNS) metastases. Concomitant disease/medical history: Patients with any known or suspected autoimmune diseases. Hypertension. Peripheral neuropathy ≥ Grade 2. Persons with a history of unstable angina or arrhythmia. Active or uncontrolled serious infection . History of immunodeficiency. Active hepatitis B or C. interstitial lung disease or non-infectious pneumonia. Active tuberculosis. Urine protein is ≥++, and 24-hour urine protein quantitative is >1.0g. Suffered from other malignant tumors within 5 years before enrollment. Unreduced toxicity . Multiple factors that affect oral medications. Abnormal coagulation function. Major surgical treatment, open biopsy or traumatic injury within 4 weeks. Tumor has invaded the periphery of important blood vessels. Patients who have seizures. Bleeding constitution or medical history. Arterial/venous thrombotic events before enrollment or within 6 months. Live attenuated vaccine vaccination within 28 days before the study. Uncontrollable pleural, abdominal or pericardial effusion. Other uncontrollable systemic diseases. Other serious physical or mental diseases or laboratory abnormalities. Patients who the researcher thinks are not suitable for this research. Participated in clinical trials of other anti-tumor drugs within four weeks.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AK105+Anlotinib Hydrochloride+Albumin Paclitaxel<br>AK105 200mg IV Day 1 Anlotinib Hydrochloride 12mg PO once daily on Days 1-14 Albumin paclitaxel 125mg/m2 IV Days 1, 8 Cycled every 21 days until disease progression, death or toxicity is intolerable (for subjects who can continue to tolerate the treatment, albumin paclitaxel lasts for at least 6 cycles) | Drug: AK105<br>* AK105: 100mg per bottle, 200mg IV Day 1, cycled every 21 days<br>* Other names: Penpulimab;Drug: Anlotinib hydrochloride<br>* Anlotinib Hydrochloride: 12mg per capsule, 12 mg PO once daily on Days 1-14, cycled every 21 days<br>Drug: Albumin Paclitaxel<br>* Albumin paclitaxel: 100mg per bottle, 125mg/m2 IV Days 1, 8, cycled every 21 days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate (ORR) | Overall response rate (ORR) is defined as the proportion of patients with the best overall response of complete response (CR) or partial response (PR) according to RECIST 1.1. | Up to approximately 10 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease Control Rate (DCR) | DCR: Disease Control Rate, defined as the proportion of patients with the best overall response of complete response (CR) , partial response (PR) or stable disease (SD) according to RECIST 1.1. | Up to approximately 10 months | 
| Progression Free Survival (PFS) | PFS is defined as the time from the date of randomization to the date of the first documented progression or death due to any cause. | Up to approximately 10 months | 
| Overall Survival (OS) | OS: Time from date of randomization to the date of death from any cause. | Up to approximately 18 months |