A Phase 2 Study of ARX788 in unresectable and/or metastatic breast cancer with low expression of HER2.

A single arm, phase 2 study of ARX788 in unresectable and/or metastatic breast cancer with low expression of HER2. Subjects should received ≥2 lines of systemic chemotherapy regimens for recurrent or metastatic disease, and for HR positive subjects, also need to have received ≥2-line endocrine therapy ± targeted therapy (including neoadjuvant/adjuvant therapy). HER2 low expression is defined as HER2 IHC 1+ or HER2 IHC 2+ and FISH negative. The ARX788 will be administered every 3 weeks (Q3W) intravenous (IV) infusion.

Inclusion Criteria:

• Willing and able to understand and sign an informed consent inform;
• Age ≥18 years, and ≤75 years, male or female;
• Diagnosed as HR arbitrary/HER2 low expression unresectable and/or metastatic breast cancer. HER2 low expression is defined as HER2 IHC 1+ (FISH negative or FISH not done) or HER2 IHC 2+ and FISH negative;
• Received ≥2 lines of systemic chemotherapy regimens for recurrent or metastatic disease, and for HR positive subjects, also need to have received ≥2-line endocrine therapy ± targeted therapy (including neoadjuvant/adjuvant therapy);
• Never had a HER2 positive result (IHC 3+ or FISH+) in previous pathological examinations;
• Have archived or fresh tumor tissue samples for HER2 status confirmation;
• According to the RECIST 1.1 standard, there is at least one measurable lesion;
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or1; LVEF≥50%;
• Adequate organ functions;
• Acute toxicities from any prior therapy, surgery, or radiotherapy must have resolved to Grade ≤1;
• Life expectancy ≥ 3 months.

Exclusion Criteria:

• 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;
• Previous treatment with T-DM1 or other HER2-ADC drugs;
• Have other malignant tumors within 5 years before signing the informed consent form (except for non-melanoma skin cancer, cervical carcinoma in situ or other tumors that have been effectively treated, except malignant tumors that are considered cured);
• Have primary central nervous system (CNS) tumors or CNS metastases;
• 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;
• Cardiac insufficiency;
• Uncontrolled hypertension;
• Suffering severe or uncontrolled systemic diseases;
• Had chemotherapy, radiotherapy, or immunotherapy within 4 weeks before the first dose;
• Had breast cancer endocrine therapy within 2 weeks before the first dose;
• Had palliative radiotherapy for bone metastasis within 2 weeks before the first dose;
• Any uncontrolled infection, or other conditions that may limit trial compliance or interfere with evaluation;
• Current known active infection with human immunodeficiency virus (HIV), hepatitis B virus, hepatitis C virus or syphilis;
• Plan to receive major surgical treatment within 2 weeks before first dose or during the trial period, or have suffered severe traumatic injury;
• Pregnancy or lactation;
• Unwilling or unable to use acceptable methods for contraception during the entire treatment period of this trial and within 8 months after the last dose;
• Participated in other clinical trials and used other experimental drugs within 4 weeks before the first dose;
• Any mental or cognitive impairment may limit their understanding and implementation of the informed consent form;
• Not suitable for participating in this trial, such as poor compliance.