Clinical trial NCT04829604: ARX788 in HER2-positive, Metastatic Breast Cancer Subjects (ACE-Breast-03)
Official title: A Global, Phase 2 Study of ARX788 in HER2-positive Metastatic Breast Cancer Patients Who Were Previously Treated With T-DXd
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: HER2 Positive Metastatic Breast Cancer
Keywords: HER2-postive
Breast cancer
Antibody drug
Metastatic
ARX788
HER2
Lead sponsor: Ambrx, Inc.
Sponsor class: INDUSTRY
First posted: 2021-04-02
Enrollment: 71
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: One single arm, open label with intravenous infusion of ARX788 to assess the anticancer activity and safety of ARX788 in subjects with unresectable or metastatic human epidermal growth factor receptor 2 (HER2)-positive (HER2+) breast cancer.
Primary purpose: TREATMENT

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

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.

Eligibility criteria: 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

Primary outcomes:
measure: Objective response rate (ORR)
timeFrame: 2 years
Secondary outcomes:
measure: Duration of response (DOR)
timeFrame: 2 years
measure: Best overall response (BOR)
timeFrame: 2 years
measure: Disease control rate (DCR)
timeFrame: 2 years
measure: Overall survival (OS)
timeFrame: 2.5 years
measure: Progression-free survival (PFS)
timeFrame: 2 years
measure: The number of subjects experiencing adverse event TEAEs
timeFrame: 2 years
measure: Maximum serum concentration (Cmax) for ARX788
timeFrame: Cycle 1 and cycle 3
measure: Trough concentration (Ctrough) for ARX788
timeFrame: Cycle 1 and cycle 3
measure: Area under the serum concentration-time curve (AUC) for ARX788
timeFrame: Cycle 1 and cycle 3
measure: Time to response (TTR)
timeFrame: Start of treatment to first objective confirmed BOR of CR or PR, assessed for approximately 2 years
Other outcomes:
measure: Evaluate Biomarker
timeFrame: 2 years
Locations:
city: Los Angeles
country: United States
facility: Research Site
state: California
city: Los Angeles
country: United States
facility: Research Site
state: California
city: Newport Beach
country: United States
facility: Research Site
state: California
city: San Francisco
country: United States
facility: Research Site
state: California
city: Santa Barbara
country: United States
facility: Research Site
state: California
city: Torrance
country: United States
facility: Research Site
state: California
city: West Los Angeles
country: United States
facility: Research Site
state: California
city: Whittier
country: United States
facility: Research Site
state: California
city: Newark
country: United States
facility: Research Site
state: Delaware
city: Hollywood
country: United States
facility: Research Site
state: Florida
city: Orlando
country: United States
facility: Research Site
state: Florida
city: Athens
country: United States
facility: Research Site
state: Georgia
city: Atlanta
country: United States
facility: Research Site
state: Georgia
city: Chicago
country: United States
facility: Research Site
state: Illinois
city: Louisville
country: United States
facility: Research Site
state: Kentucky
city: Baton Rouge
country: United States
facility: Research Site
state: Louisiana
city: Lutherville
country: United States
facility: Research Site
state: Maryland
city: Silver Spring
country: United States
facility: Research Site
state: Maryland
city: Boston
country: United States
facility: Research Site
state: Massachusetts
city: Bolivar
country: United States
facility: Research Site
state: Missouri
city: Saint Louis
country: United States
facility: Research Site
state: Missouri
city: Omaha
country: United States
facility: Research Site
state: Nebraska
city: Las Vegas
country: United States
facility: Research Site
state: Nevada
city: Camden
country: United States
facility: Research Site
state: New Jersey
city: Albuquerque
country: United States
facility: Research Site
state: New Mexico
city: Bronx
country: United States
facility: Research Site
state: New York
city: New Hyde Park
country: United States
facility: Research Site
state: New York
city: New York
country: United States
facility: Research Site
state: New York
city: New York
country: United States
facility: Research Site
state: New York
city: New York
country: United States
facility: Research Site
state: New York
city: Shirley
country: United States
facility: Research Site
state: New York
city: Portland
country: United States
facility: Research Site
state: Oregon
city: Tigard
country: United States
facility: Research Site
state: Oregon
city: Philadelphia
country: United States
facility: Research Site
state: Pennsylvania
city: Chattanooga
country: United States
facility: Research Site
state: Tennessee
city: Nashville
country: United States
facility: Research Site
state: Tennessee
city: Austin
country: United States
facility: Research Site
state: Texas
city: Dallas
country: United States
facility: Research Site
state: Texas
city: Houston
country: United States
facility: Research Site
state: Texas
city: Plano
country: United States
facility: Research Site
state: Texas
city: Tyler
country: United States
facility: Research Site
state: Texas
city: Norfolk
country: United States
facility: Research Site
state: Virginia
city: Tacoma
country: United States
facility: Research Site
state: Washington
city: South Brisbane
country: Australia
facility: Research Site
state: Queensland
city: Woolloongabba
country: Australia
facility: Research Site
state: Queensland
city: Clayton
country: Australia
facility: Research Site
state: Victoria
city: Frankston
country: Australia
facility: Research Site
state: Victoria
city: Geelong
country: Australia
facility: Research Site
state: Victoria
city: Melbourne
country: Australia
facility: Research Site
state: Victoria
city: Ringwood East
country: Australia
facility: Research Site
state: Victoria
city: Nedlands
country: Australia
facility: Research Site
state: Western Australia
city: Avignon Cedex 09
country: France
facility: Research Site
city: La Rochelle
country: France
facility: Research Site
city: Le Mans
country: France
facility: Research Site
city: Nice
country: France
facility: Research Site
city: Toulouse CEDEX 9
country: France
facility: Research Site
city: Daegu
country: Korea, Republic of
facility: Research Site
city: Goyang-si
country: Korea, Republic of
facility: Research Site
city: Seongnam-si
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Suwon
country: Korea, Republic of
facility: Research Site
Study officials:
affiliation: Ambrx, Inc.
name: Ambrx
role: STUDY_DIRECTOR
References: