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Trial record 1 of 7 for:    ARX788
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ARX788 in HER2-positive, Metastatic Breast Cancer Subjects (ACE-Breast-03) (ACE-Breast03)

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ClinicalTrials.gov Identifier: NCT04829604
Recruitment Status : Recruiting
First Posted : April 2, 2021
Last Update Posted : January 6, 2022
Sponsor:
Information provided by (Responsible Party):
Ambrx, Inc.

Brief Summary:
A Global, Phase 2 Study of ARX788 in HER2-positive, Metastatic Breast Cancer Patients whose Disease is Resistant or Refractory to T-DM1, and/or T-DXd, and/or Tucatinib-containing Regimens

Condition or disease Intervention/treatment Phase
HER2 Positive Metastatic Breast Cancer Drug: ARX788 Phase 2

Detailed Description:
A Global, Single Arm, Phase 2 Study of ARX788 in HER2-positive, Metastatic Breast Cancer Patients whose disease is Resistant or Refractory to T-DM1, and/or T-DXd, and/or Tucatinib-containing Regimens. The ARX788 will be administered every 4 weeks (Q4W) intravenous (IV) infusion.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 210 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description: One single arm, open label with intravenous infusion of ARX788
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Global, Phase 2 Study of ARX788 in HER2-positive, Metastatic Breast Cancer Patients Whose Disease is Resistant or Refractory to T-DM-1 or T-DXd, and/or Tucatinib-containing Regimens
Actual Study Start Date : April 5, 2021
Estimated Primary Completion Date : December 2023
Estimated Study Completion Date : February 2025

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arm Intervention/treatment
Experimental: HER2 positive metastatic breast cancer subjects whose disease is resistant or refractory

This global Phase 2 study is designed to assess anticancer activity and safety of ARX788 in HER2 positive metastatic breast cancer subjects whose disease is resistant or refractory to T-DM1, and/or T-DXd, and/or tucatinib-containing regimens.

The investigational medicinal product (IMP), ARX788, will be administered every 4 weeks (Q4W) 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 Name: antibody drug conjugate (ADC)




Primary Outcome Measures :
  1. Objective response rate (ORR) [ Time Frame: 2 Years ]

    The confirmed objective response rate (ORR) of ARX788 based on RECIST 1.1 in HER2-positive breast cancer subjects whose disease is resistant or refractory to T-DM1, and/or T-DXd, and/or tucatinib-containing regimens.

    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 Outcome Measures :
  1. 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.

  2. Best percent change in the sum of the longest diameters of measurable tumors [ Time Frame: 2 years ]
    The percent change at the best response data point compared to baseline.

  3. 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)

  4. 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.

  5. 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

  6. 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.

  7. 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.

  8. Maximum serum concentration (Cmax) for ARX788, total antibody, and pAF-AS269 [ Time Frame: Cycle 1 and cycle 3 ]
    Pharmacokinetic parameter maximum serum concentration (Cmax) for ARX788, total antibody, and pAF-AS269

  9. Trough concentration (Ctrough) for ARX788, total antibody, and pAF-AS269 [ Time Frame: Cycle 1 and cycle 3 ]
    Pharmacokinetic parameter trough concentration (Ctrough) for ARX788, total antibody, and pAF-AS269

  10. Area under the serum concentration-time curve (AUC) for ARX788, total antibody, and pAF-AS269 [ Time Frame: Cycle 1 and cycle 3 ]
    Pharmacokinetic parameter area under the serum concentration-time curve (AUC) for ARX788, total antibody, and pAF-AS269

  11. Incidence of anti-drug antibodies (ADAs) [ Time Frame: 2 years ]
    Incidence of anti-drug antibodies (ADAs) following intravenous administration of ARX788 in participants with HER2-positive metastatic breast cancer



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age ≥ 18 years and older
  • Life expectancy > 3 months
  • Eastern Cooperative Oncology Group Performance Status ≤ 1
  • Metastatic breast cancer subjects previously treated with T DM1, and/or T-DXd, and/or tucatinib-containing regimens.
  • 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 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.
  • Female subjects must be surgically sterile, or have a monogamous partner who is surgically sterile, or at postmenopausal, or who commits to use an acceptable form of birth control; male subjects must be sterile (biologically or surgically) or commit to the use of a reliable method of birth control

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 within 12 months
  • History of ocular events, or any current ongoing active ocular infections.
  • 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.
  • Clinically significant surgical intervention (excluding diagnostic biopsy) within 21 days of the first dose of ARX788
  • Radiotherapy administered less than 21 days prior to the first dose of ARX788, or localized palliative radiotherapy administered less than 7 days prior to the first dose of ARX788, or radiotherapy-induced toxicity of Grade 2 or greater based on NCI-CTCAE v 5.0.
  • Pregnancy or breast feeding.
  • Known active HCV, HBV, and/or HIV infection.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04829604


Contacts
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Contact: Trial Inquiry (858) 875-2400 breast03trialinquiry@ambrx.com

Locations
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Sponsors and Collaborators
Ambrx, Inc.
Investigators
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Study Director: Ambrx Ambrx, Inc.
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Responsible Party: Ambrx, Inc.
ClinicalTrials.gov Identifier: NCT04829604    
Other Study ID Numbers: ACE-Breast-03
First Posted: April 2, 2021    Key Record Dates
Last Update Posted: January 6, 2022
Last Verified: January 2022

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Ambrx, Inc.:
HER2-postive
Breast cancer
Antibody drug
Metastatic
ARX788
HER2
Additional relevant MeSH terms:
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Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Immunoconjugates
Immunologic Factors
Physiological Effects of Drugs