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

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

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

Study Overview

• Status: Active, not recruiting
• Conditions: HER2 Positive Metastatic Breast Cancer
• Intervention / Treatment: Drug: ARX788

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 72
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • Victoria
    • Frankston, Victoria, Australia, 3199
      • Research Site
    • Geelong, Victoria, Australia, 3220
      • Research Site
  • Western Australia
    • Nedlands, Western Australia, Australia, 6009
      • Research Site
• South Korea
  • Daegu, South Korea, 42601
    • Research Site
  • Seongnam-si, South Korea, 13620
    • Research Site
  • Seoul, South Korea, 02841
    • Research Site
  • Seoul, South Korea, 03722
    • Research Site
  • Seoul, South Korea, 05505
    • Research Site
• United States
  • California
    • Los Angeles, California, United States, 90033
      • Research Site
    • Newport Beach, California, United States, 92663
      • Research Site
    • San Francisco, California, United States, 94158
      • Research Site
    • Whittier, California, United States, 90602
      • Research Site
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Research Site
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Research Site
  • Kentucky
    • Louisville, Kentucky, United States, 40207
      • Research Site
  • Maryland
    • Silver Spring, Maryland, United States, 20904
      • Research Site
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Research Site
  • Missouri
    • St Louis, Missouri, United States, 63110
      • Research Site
  • Nebraska
    • Omaha, Nebraska, United States, 68130
      • Research Site
  • Nevada
    • Las Vegas, Nevada, United States, 89128
      • Research Site
  • New Jersey
    • Camden, New Jersey, United States, 08103
      • Research Site
  • New York
    • New Hyde Park, New York, United States, 11042
      • Research Site
    • New York, New York, United States, 10028
      • Research Site
    • Shirley, New York, United States, 11967
      • Research Site
    • The Bronx, New York, United States, 10469
      • Research Site
  • Oregon
    • Portland, Oregon, United States, 97213
      • Research Site
    • Tigard, Oregon, United States, 97223
      • Research Site
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Research Site
  • Texas
    • Dallas, Texas, United States, 75246
      • Research Site
    • Houston, Texas, United States, 77030
      • Research Site
    • San Antonio, Texas, United States, 78229
      • Research Site
  • Virginia
    • Norfolk, Virginia, United States, 23502
      • Research Site
  • Washington
    • Tacoma, Washington, United States, 98405
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 HER2 positive breast cancer per ASCO-CAP guidelines, documented in a CLIA lab pathology report
• Subjects must have had prior treatment with no more than 5 prior regimens of systemic treatment HER-2 targeting therapy or chemotherapy 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, vitiligo, Grade 2 peripheral neuropathy, or endocrine toxicities that are stable on hormone replacement.
• 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 requirement for supplemental oxygen.
• Any active ocular infections or chronic corneal disorders
• History of congestive heart failure, unstable angina pectoris, unstable atrial fibrillation, cardiac arrhythmia, or myocardial infarction within 6 months prior to enrollment
• Grade 3 to 4 peripheral neuropathy (NCI CTCAE v 5.0).
• History of unstable central nervous system (CNS) metastases
• Radiotherapy outside of the brain administered < 7 days prior to first dose of ARX788
• 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

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: ARX788; The investigational medicinal product (IMP), ARX788, will be administered every 3 weeks (Q3W) by intravenous (IV) infusion.	Drug: ARX788; 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; Other Names: antibody drug conjugate (ADC)

What is the study measuring?

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
Disease control rate (DCR)	DCR is defined as the proportion of complete response (CR), partial response (PR), and stable disease (SD) rates.	2 years
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
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
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 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.	2.5 years
Maximum serum concentration (Cmax) for ARX788	Pharmacokinetic parameter maximum serum concentration (Cmax) for ARX788, ADC, ADA, total antibody, and pAF-AS269	Cycle 1 and cycle 3
Time to response (TTR)	Time it takes for patient to respond to study treatment	Start of treatment to first objective confirmed BOR of CR or PR, assessed for approximately 2 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluate Biomarker	To evaluate exploratory blood- and tissue-based biomarkers related to study drug response	2 years

Collaborators and Investigators

• Sponsor: Ambrx, Inc.
• Investigators: Study Director: Ambrx, Ambrx, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): October 26, 2021
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): June 1, 2027

Study Registration Dates

• First Submitted: March 18, 2021
• First Submitted That Met QC Criteria: April 1, 2021
• First Posted (Actual): April 2, 2021

Study Record Updates

• Last Update Posted (Actual): March 9, 2026
• Last Update Submitted That Met QC Criteria: March 6, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: HER2; Breast cancer; Metastatic; HER2-postive; Antibody drug; ARX788
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Site; Neoplasms; Neoplastic Processes; Skin Diseases; Breast Diseases; Pathological Conditions, Signs and Symptoms; Skin and Connective Tissue Diseases; Breast Neoplasms; Neoplasm Metastasis; Immunologic Factors; Physiological Effects of Drugs; Amino Acids, Peptides, and Proteins; Proteins; Pharmacologic Actions; Chemical Actions and Uses; Antibodies; Immunoglobulins; Blood Proteins; Serum Globulins; Globulins; Immunoconjugates; ARX788
• Other Study ID Numbers: ACE-Breast-03

Drug and device information, study documents

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