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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Breast Neoplasm Female
• Intervention / Treatment: Drug: AK105; Drug: Anlotinib hydrochloride; Drug: Albumin Paclitaxel

• Study Type: Interventional
• Enrollment (Anticipated): 42
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Tao Sun, Doctor; Phone Number: 0086-18624005672; Email: lnszl2021@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Female aged 18-75 years old.
• ECOG 0 or 1 point.

• Advanced triple-negative invasive breast cancer :

  1. The pathological classification is triple negative, specifically:

     1. ER negative: IHC<1%.
     2. PR negative: IHC<1%.
     3. HER2 negative: IHC-/+ or IHC++ but FISH/CISH is negative.
  2. 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:

  1. Routine blood test:

     1. Hemoglobin (HB) ≥90 g/L.
     2. Neutrophil count (ANC) ≥1.5×109/L.
     3. Platelet count (PLT) ≥100×109/L.

  2. Biochemical test:

     1. Total bilirubin≤1.5×ULN (upper limit of normal).
     2. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5×ULN; if there is liver metastasis, ALT and AST ≤ 5×ULN.
     3. 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:

  1. Patients with any known or suspected autoimmune diseases.
  2. Hypertension.
  3. Peripheral neuropathy ≥ Grade 2.
  4. Persons with a history of unstable angina or arrhythmia.
  5. Active or uncontrolled serious infection .
  6. History of immunodeficiency.
  7. Active hepatitis B or C.
  8. interstitial lung disease or non-infectious pneumonia.
  9. Active tuberculosis.
  10. Urine protein is ≥++, and 24-hour urine protein quantitative is >1.0g.
  11. Suffered from other malignant tumors within 5 years before enrollment.
  12. Unreduced toxicity .
  13. Multiple factors that affect oral medications.
  14. Abnormal coagulation function.
  15. Major surgical treatment, open biopsy or traumatic injury within 4 weeks.
  16. Tumor has invaded the periphery of important blood vessels.
  17. Patients who have seizures.
  18. Bleeding constitution or medical history.
  19. Arterial/venous thrombotic events before enrollment or within 6 months.
  20. Live attenuated vaccine vaccination within 28 days before the study.
  21. Uncontrollable pleural, abdominal or pericardial effusion.
  22. 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AK105+Anlotinib Hydrochloride+Albumin Paclitaxel; 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; AK105: 100mg per bottle, 200mg IV Day 1, cycled every 21 days; Other Names: Penpulimab; Drug: Anlotinib hydrochloride; Anlotinib Hydrochloride: 12mg per capsule, 12 mg PO once daily on Days 1-14, cycled every 21 days; Drug: Albumin Paclitaxel; Albumin paclitaxel: 100mg per bottle, 125mg/m2 IV Days 1, 8, cycled every 21 days

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Liaoning Tumor Hospital & Institute
• Collaborators: Huludao central hospital; Anshan Tumor Hospital; Chaoyang Central Hospital; Fukuang General Hospital of Liaoning health industry group
• Investigators: Principal Investigator: Tao Sun, Doctor, Liaoning Tumor Hospital & Institute

Study record dates

Study Major Dates

• Study Start (Anticipated): July 1, 2022
• Primary Completion (Anticipated): March 1, 2024
• Study Completion (Anticipated): March 1, 2024

Study Registration Dates

• First Submitted: February 8, 2022
• First Submitted That Met QC Criteria: February 8, 2022
• First Posted (Actual): February 17, 2022

Study Record Updates

• Last Update Posted (Actual): July 12, 2022
• Last Update Submitted That Met QC Criteria: July 11, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Triple Negative Breast Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Paclitaxel
• Other Study ID Numbers: ALTER-BC-003

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No