ARX788 in HER2-positive, Metastatic Breast Cancer Subjects (ACE-Breast-03)

Study Overview
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Brief Summary
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A Global, Phase 2 Study of ARX788 in HER2-positive Metastatic Breast Cancer Patients who were previously treated with T-DXd

Detailed Description
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A Global, Single Arm, Phase 2 Study of ARX788 in HER2-positive Metastatic Breast Cancer Patients who were previously treated with T-DXd. The ARX788 will be administered every 3 weeks (Q3W) intravenous (IV) infusion.

Official Title
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A Global, Phase 2 Study of ARX788 in HER2-positive Metastatic Breast Cancer Patients Who Were Previously Treated With T-DXd

Conditions
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HER2 Positive Metastatic Breast Cancer

Intervention / Treatment
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* Drug: ARX788


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Age ≥ 18 years and older Life expectancy ≥ 6 months Unresectable or metastatic breast cancer subjects Presence of at least one measurable lesion per RECIST v 1.1 Subjects must have an adequate tumor sample available for confirmation of HER2 status Subjects must have had prior treatment with no more than 5 prior regimens of systemic treatment in the metastatic setting. One of these prior treatments must have been treatment with T-DXd. Subjects with stable brain metastases Acute toxicities from any prior therapy, surgery, or radiotherapy must have resolved to Grade ≤1 as per the NCI-CTCAE v 5.0, except alopecia Adequate organ functions Willing and able to understand and sign an informed consent inform and to comply with all aspects of the protocol Key Exclusion Criteria: Any subject who meets any of the following criteria is excluded from the study: History of allergic reactions to any component of ARX788. Prior history of interstitial lung disease, pneumonitis, or other clinically significant lung disease Any active ocular infections or chronic corneal disorders History of congestive heart failure, unstable angina pectoris, unstable atrial fibrillation, or cardiac arrhythmia within 12 months prior to enrollment Grade 3 to 4 peripheral neuropathy (NCI CTCAE v 5.0). Patients with Grade 2 neuropathy can be enrolled at investigator's discretion History of unstable central nervous system (CNS) metastases Current severe, uncontrolled systemic disease (eg, clinically significant cardiovascular, pulmonary, or metabolic diseases) Any uncontrollable intercurrent illness, infection (including subjects with active, symptomatic Covid-19 infections), or other conditions that could limit study compliance or interfere with assessments Exposure to any other investigational or commercial anticancer agents or therapies administered with the intention to treat malignancy within 14 days before the first dose of ARX788

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

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
Interventional Model Description: One single arm, open label with intravenous infusion of ARX788
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ARX788<br>The investigational medicinal product (IMP), ARX788, will be administered every 3 weeks (Q3W) by intravenous (IV) infusion. | Drug: ARX788<br>* The active pharmaceutical ingredient in ARX788 is an antibody drug conjugate (ADC) consisting of a humanized anti-HER2 monoclonal antibody (mAb) (IgG1κ) covalently conjugated to two microtubule-disrupting payloads AS269<br>* Other names: antibody drug conjugate (ADC);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate (ORR) | To evaluate the confirmed objective response rate (ORR) as determined by Investigator assessment based on Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) following treatment with ARX788. The ORR is defined as the number of subjects with a BOR of CR or PR divided by the number of response evaluable subjects. | 2 Years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of response (DOR) | DOR is defined as the time between the date of first response and the date of disease progression or death, whichever occurs first, will be computed for subjects with a BOR of CR or PR. | 2 years | 
| Best overall response (BOR) | BOR is defined as the best response recorded from the start of the treatment until disease progression/recurrence (taking as reference for progressive disease the smallest measurements recorded since the treatment started) | 2 year | 
| Disease control rate (DCR) | DCR is defined as the proportion of complete response (CR), partial response (PR), and stable disease (SD) rates. | 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 year | 
| 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 | 
| The number of subjects experiencing adverse event TEAEs | 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 | 
| Maximum serum concentration (Cmax) for ARX788 | Pharmacokinetic parameter maximum serum concentration (Cmax) for ARX788, ADC, total antibody, and pAF-AS269 | Cycle 1 and cycle 3 | 
| Trough concentration (Ctrough) for ARX788 | Pharmacokinetic parameter trough concentration (Ctrough) for ARX788, ADC, total antibody, and pAF-AS269 | Cycle 1 and cycle 3 | 
| Area under the serum concentration-time curve (AUC) for ARX788 | Pharmacokinetic parameter area under the serum concentration-time curve (AUC) for ARX788, ADC, total antibody, and pAF-AS269 | Cycle 1 and cycle 3 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HER2-postive, Breast cancer, Antibody drug, Metastatic, ARX788, HER2