AK105 Plus Anlotinib Hydrochloride Combined With Albumin Paclitaxel as a First-line Therapy in Patients With Advanced Triple-negative Breast Cancer: a Single-arm, Multicentre, Prospective, Phase II Clinical Trial.

• Status: Not yet recruiting
• Trial end date: 2024-03-01
• Target enrollment: 0
• Participant gender: Female

Summary

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Liaoning Tumor Hospital & Institute
• Collaborators: Anshan Tumor Hospital; Chaoyang Central Hospital; Fukuang General Hospital of Liaoning health industry group; Huludao central hospital
• Treatments: Paclitaxel

Criteria

Inclusion Criteria:

• Female aged 18-75 years old.

• ECOG 0 or 1 point.

• Advanced triple-negative invasive breast cancer confirmed by histopathological examination, and meet the following conditions at the same time: 1) 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, preferentially based on the pathology of metastases , If the pathology of the metastasis is unavailable, the pathology of the original tumor shall be used as the basis; 2) Tumor staging: locally advanced or recurrent/metastatic breast cancer; locally advanced breast cancer must be confirmed by the investigator that it cannot be resected by radical surgery; patients in the recurrent and metastatic stage have not received systemic anti-tumor treatment for recurrent and metastatic lesions in the past.

• 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 (extracranial) 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: 1) Routine blood test (without blood transfusion within 14 days): a. Hemoglobin (HB) ≥90 g/L; b. Neutrophil count (ANC) ≥1.5×109/L; c. Platelet count (PLT) ≥100×109/L; 2) Biochemical test: a. Total bilirubin≤1.5×ULN (upper limit of normal); b. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5×ULN; if there is liver metastasis, ALT and AST ≤ 5×ULN; c. Serum creatinine (Cr) ≤1.5ULN or creatinine clearance ≥60mL/min (Cockcroft-Gault formula).

• Female patients of childbearing age must undergo a serum pregnancy test within 3 days before the first medication, and the result must be negative. Female patients of childbearing age must agree to use high-efficiency methods of contraception during the study period and within 180 days after the last administration of the study drug.

• Volunteer to participate in this study, sign an informed consent form, and have good compliance.

Exclusion Criteria:

• Female subjects who are pregnant, lactating or planning to become pregnant during the study period.

• Patients who are known to be allergic to any of the drugs in the study.

• Patients who have previously received PD-1/PD-L1 antibody, CTLA-4 antibody, or anti-vascular targeted therapy.

• Patients with central nervous system (CNS) metastases (or obvious symptoms) who have been judged to have rapid progress of metastases.

• Concomitant disease/medical history: 1) Patients with any known or suspected autoimmune diseases, except: autoimmune thyroiditis and type I diabetes patients with stable blood sugar control; 2) Patients with hypertension who cannot be well controlled by a single antihypertensive drug treatment (systolic blood pressure ≥150 mmHg, diastolic blood pressure ≥90 mmHg); 3) Peripheral neuropathy ≥ Grade 2; 4) Persons with a history of unstable angina; patients newly diagnosed with angina within 3 months before screening or with myocardial infarction within 6 months before screening; arrhythmia (including QTcF: male ≥450 ms) need long-term antiarrhythmic use Drugs and New York Heart Association grade ≥ Grade II cardiac insufficiency; 5) Active or uncontrolled serious infection (≥NCI CTCAE V5.0 Grade 2 infection); 6) Have a history of immunodeficiency, including HIV positive or other acquired or congenital immunodeficiency diseases, or a history of organ transplantation; 7) Patients with active hepatitis B or C; 8) Previously suffering from interstitial lung disease and non-infectious pneumonia requiring steroid treatment; 9) Have a history of active tuberculosis; 10) Urine routines suggest that urine protein is ≥++, and the 24-hour urine protein quantitative is confirmed to be greater than 1.0g; 11) Suffered from other malignant tumors within 5 years before enrollment, except for malignant tumors that have been cured or have stable disease; 12) Unreduced toxicity that is higher than NCI CTCAE V5.0 Grade 2 or above due to any previous treatment, but does not include hair loss; 13) Those who have multiple factors that affect oral medications (such as inability to swallow, gastrointestinal resection, chronic diarrhea and intestinal obstruction, etc.); 14) Abnormal coagulation function (PT>16s, APTT>43s, TT>21s, Fbg<2g/L), those with bleeding tendency (14 days before enrollment must meet: prothrombin without anticoagulant Time International Normalized Ratio (INR) is within the normal range); patients treated with anticoagulants or vitamin K antagonists such as warfarin, heparin or their analogs; under the premise of INR ≤ 1.5, use is allowed for prevention purposes Low-dose warfarin (1 mg orally, once a day) or low-dose aspirin (do not exceed 100 mg per day); 15) Patients who received major surgical treatment, open biopsy or obvious traumatic injury within 4 weeks before enrollment; 16) Patients whose imaging shows that the tumor has invaded the periphery of important blood vessels or the investigator judges that the tumor is very likely to invade important blood vessels and cause fatal hemorrhage during the follow-up study; 17) Patients who have seizures and need treatment; 18) Regardless of the severity, patients with any bleeding constitution or medical history; patients with any bleeding or bleeding event ≥ NCI CTCAE V5.0 grade 3 within 4 weeks before enrollment, and unhealed wounds, ulcers or fractures; 19) Those who have had arterial/venous thrombotic events before enrollment or within 6 months, such as cerebrovascular accidents (including temporary ischemic attacks), deep vein thrombosis and pulmonary embolism; 20) The history of live attenuated vaccine vaccination within 28 days before the first study medication or the expected live attenuated vaccine vaccination during the study period; 21) Uncontrollable moderate to large amounts of pleural effusion, abdominal effusion or pericardial effusion that require repeated drainage; 22) Other uncontrollable systemic diseases (such as diabetes, etc.);

• There are other serious physical or mental diseases or laboratory abnormalities that may increase the risk of participating in the research or interfere with the results of the research, as well as patients who the researcher thinks are not suitable for participating in this research.

• Patients who have participated in clinical trials of other anti-tumor drugs within four weeks.