ARX788 in HER2-positive Breast Cancer Patients With Brain Metastases

A Prospective, Single-arm, Single-center Phase II Clinical Study of Recombinant Humanized Anti-HER2 Monoclonal Antibody-AS269 Conjugate (ARX788) in the Treatment of HER2-positive Breast Cancer Patients With Brain Metastases

A Phase 2 Study of ARX788 in HER2-positive, Metastatic Breast Cancer Patients whose Disease is resistant or refractory to Tyrosine kinase inhibitors (TKI).

Study Overview

• Status: Recruiting
• Conditions: HER2-positive, Metastatic Breast Cancer
• Intervention / Treatment: Drug: ARX788

Detailed Description

This is an open-label, single arm, phase 2 study of ARX788 in HER2-positive, metastatic breast cancer patients whose disease is resistant or refractory to TKI. The ARX788 will be administered every 3 weeks (Q3W) intravenous (IV) infusion. In this study, Simon's two-stage design is used. Subjects received treatment until disease progression, intolerable toxicity, withdrawal from the study, or discontinuation judged by the investigator. Drug efficacy and safety data will be collected.

• Study Type: Interventional
• Enrollment (Anticipated): 32
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Ting Li; Phone Number: 86-18121299346; Email: cinderellaliting@126.com

Study Locations

• China
  • Shanghai, China, 200032
    • Recruiting
    • Fudan University Shanghai Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age ≥18 years, and ≤75 years, male or female;
• Eastern Cooperative Oncology Group (ECOG) performance status of 0~2;
• Breast cancer patients diagnosed as HR arbitrary/HER2-positive by pathological examination;
• Metastatic breast cancer subjects previously treated with trastuzumab, taxane and EGFR-TKI-containing regimens;
• MRI confirmed brain metastasis with at least one intracranial parenchymal untreated metastatic lesion;
• Mannitol, bevacizumab, or hormone therapy is allowed before enrollment;
• Adequate organ functions;
• Acute toxicities from any prior therapy, surgery, or radiotherapy must have resolved to Grade ≤1.
• Patients who participate in the trial voluntarily, sign an informed consent, have good compliance and are willing to comply with the follow-up visit.

Exclusion Criteria:

• Pneumomeningeal metastases or cystic metastases confirmed by MRI or lumbar puncture;
• Uncontrolled third space effusion;
• Previous treatment with T-DM1 or other HER2-ADC drugs;
• Received a whole-brain radiotherapy, chemotherapy, or surgery within 2 weeks prior to the first dose of ARX788, or trastuzumab-targeted therapy or endocrine therapy within 1 week, or palliative radiotherapy for bone metastases within 2 weeks;
• Prior history of interstitial pulmonary disease requiring hormone therapy, drug-induced interstitial pulmonary disease, radiation pneumonia, or current clinically active interstitial pulmonary disease;
• Suffering from keratitis, corneal diseases, retinal diseases or active eye infections that require intervention;
• Unwilling or unable to stop wearing contact lenses for the duration of the study;
• Participated in other clinical trials within 2 weeks prior to enrollment;
• Receiving any antitumor therapy for any other tumor, bevacizumab for the control of brain edema and bisphosphonates for the treatment of bone metastases or the prevention of osteoporosis are the exception;
• With a history of any malignancies other than breast cancer in the past 5 years, excluding cured cervical carcinoma in situ, basal cell carcinoma of the skin or squamous cell carcinoma of the skin;
• Cardiac insufficiency;
• Uncontrolled hypertension;
• History of allergic reactions to any component of ARX788, or with a history of protein drug allergy, a history of specific allergies (asthma, rheumatism, eczematous dermatitis), or a history of other severe allergic reactions, who are unsuitable for ARX788 treatment as per the investigator's judgments;
• Pregnancy or lactation;
• History of immunodeficiency, including HIV-positive, or other acquired or congenital immunodeficiency diseases, or a history of organ transplantation;
• Current known active infection with human immunodeficiency virus (HIV), hepatitis B virus, hepatitis C virus or syphilis;
• History of neurological or psychiatric disorder, including epilepsy or dementia;
• Suffering severe or uncontrolled systemic diseases.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: ARX788	Drug: ARX788; 1.5 mg/kg IV infusion on Day 1 of each 21-day treatment cycle.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Central nervous system (CNS) clinical benefit rate (CBR)	CNS CBR is defined as the percentage of subjects who have achieved complete response, partial response, and stable disease according to the Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) criteria	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival (PFS)	PFS is defined as the time between date of first dose of study therapy and date of progression or death, whichever occurs first, will be computed for response evaluable subjects. Subjects will be censored at time of subsequent therapy	2 years
Overall survival (OS)	Overall survival (OS) is defined as the time from first dose of study therapy to the date of death (any cause). Subjects who are alive will be censored at the last known time that the subject was alive	2 years
Site of first progression	Record the organs where the disease first progressed during the study	2 years
The number of subjects experiencing adverse events	Patient safety and adverse events (AEs) will be evaluated using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v.5.0. All AEs and serious adverse events (SAEs) will be assessed to determine the safety and tolerability of the treatment.	2 years

Collaborators and Investigators

• Sponsor: Fudan University

Study record dates

Study Major Dates

• Study Start (ACTUAL): July 14, 2021
• Primary Completion (ANTICIPATED): December 30, 2022
• Study Completion (ANTICIPATED): June 30, 2023

Study Registration Dates

• First Submitted: August 22, 2021
• First Submitted That Met QC Criteria: August 22, 2021
• First Posted (ACTUAL): August 24, 2021

Study Record Updates

• Last Update Posted (ACTUAL): June 1, 2022
• Last Update Submitted That Met QC Criteria: May 30, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Keywords: HER2-positive breast cancer; ARX788; Brain metastasis
• Additional Relevant MeSH Terms: Pathologic Processes; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Neoplastic Processes; Central Nervous System Neoplasms; Nervous System Neoplasms; Breast Neoplasms; Neoplasm Metastasis; Brain Neoplasms
• Other Study ID Numbers: ACE-Breast-06

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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