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

Overview

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

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

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: N/A
    • Intervention Model: Single Group Assignment
    • Primary Purpose: Treatment
    • Masking: None (Open Label)
  • Study Primary Completion Date: June 2025

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.

Interventions

  • 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

Arms, Groups and Cohorts

  • Experimental: ARX788
    • The investigational medicinal product (IMP), ARX788, will be administered every 3 weeks (Q3W) by intravenous (IV) infusion.

Clinical Trial Outcome Measures

Primary Measures

  • Objective response rate (ORR)
    • Time Frame: 2 Years
    • 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.

Secondary Measures

  • Duration of response (DOR)
    • Time Frame: 2 years
    • 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.
  • Best overall response (BOR)
    • Time Frame: 2 year
    • 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)
  • Disease control rate (DCR)
    • Time Frame: 2 years
    • DCR is defined as the proportion of complete response (CR), partial response (PR), and stable disease (SD) rates.
  • Overall survival (OS)
    • Time Frame: 2 year
    • 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.
  • Progression-free survival (PFS)
    • Time Frame: 2 years
    • 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
  • The number of subjects experiencing adverse event TEAEs
    • Time Frame: 2 years
    • 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.
  • Maximum serum concentration (Cmax) for ARX788
    • Time Frame: Cycle 1 and cycle 3
    • Pharmacokinetic parameter maximum serum concentration (Cmax) for ARX788, ADC, total antibody, and pAF-AS269
  • Trough concentration (Ctrough) for ARX788
    • Time Frame: Cycle 1 and cycle 3
    • Pharmacokinetic parameter trough concentration (Ctrough) for ARX788, ADC, total antibody, and pAF-AS269
  • Area under the serum concentration-time curve (AUC) for ARX788
    • Time Frame: Cycle 1 and cycle 3
    • Pharmacokinetic parameter area under the serum concentration-time curve (AUC) for ARX788, ADC, total antibody, and pAF-AS269

Participating in This Clinical Trial

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

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Ambrx, Inc.
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Ambrx, Study Director, Ambrx, Inc.
  • Overall Contact(s)
    • Trial Inquiry, (858) 875-2400, breast03trialinquiry@ambrx.com

Clinical trials entries are delivered from the US National Institutes of Health and are not reviewed separately by this site. Please see the identifier information above for retrieving further details from the government database.

At TrialBulletin.com, we keep tabs on over 200,000 clinical trials in the US and abroad, using medical data supplied directly by the US National Institutes of Health. Please see the About and Contact page for details.