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

HER2 Positive Metastatic Breast Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04829604
• Other study ID #: ACE-Breast-03
• Status: Recruiting
• Phase: Phase 2
• Start date: October 26, 2021
• Est. completion date: December 2026

Study information

• Verified date: June 2024
• Source: Ambrx, Inc.
• Contact: Trial Inquiry
• Phone: (858) 875-2400
• Email: breast03trialinquiry[@]ambrx.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 71
• Est. completion date: December 2026
• Est. primary completion date: June 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Breast Neoplasms
• HER2 Positive Metastatic Breast Cancer

Intervention

Drug:
• ARX788
The active pharmaceutical ingredient in ARX788 is an antibody drug conjugate (ADC) consisting of a humanized anti-HER2 monoclonal antibody (mAb) (IgG1?) covalently conjugated to two microtubule-disrupting payloads AS269

Locations

Country	Name	City	State
Australia	Research Site	Clayton	Victoria
Australia	Research Site	Frankston	Victoria
Australia	Research Site	Geelong	Victoria
Australia	Research Site	Melbourne	Victoria
Australia	Research Site	Nedlands	Western Australia
Australia	Research Site	Ringwood East	Victoria
Australia	Research Site	South Brisbane	Queensland
Australia	Research Site	Woolloongabba	Queensland
France	Research Site	Avignon Cedex 09
France	Research Site	La Rochelle
France	Research Site	Le Mans
France	Research Site	Nice
France	Research Site	Toulouse CEDEX 9
Korea, Republic of	Research Site	Daegu
Korea, Republic of	Research Site	Goyang-si
Korea, Republic of	Research Site	Seongnam-si
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Suwon
United States	Research Site	Albuquerque	New Mexico
United States	Research Site	Athens	Georgia
United States	Research Site	Atlanta	Georgia
United States	Research Site	Austin	Texas
United States	Research Site	Baton Rouge	Louisiana
United States	Research Site	Bolivar	Missouri
United States	Research Site	Boston	Massachusetts
United States	Research Site	Bronx	New York
United States	Research Site	Chattanooga	Tennessee
United States	Research Site	Chicago	Illinois
United States	Research Site	Dallas	Texas
United States	Research Site	Hollywood	Florida
United States	Research Site	Houston	Texas
United States	Research Site	Las Vegas	Nevada
United States	Research Site	Los Angeles	California
United States	Research Site	Los Angeles	California
United States	Research Site	Louisville	Kentucky
United States	Research Site	Lutherville	Maryland
United States	Research Site	Nashville	Tennessee
United States	Research Site	New Hyde Park	New York
United States	Research Site	New York	New York
United States	Research Site	New York	New York
United States	Research Site	New York	New York
United States	Research Site	Newark	Delaware
United States	Research Site	Newport Beach	California
United States	Research Site	Norfolk	Virginia
United States	Research Site	Omaha	Nebraska
United States	Research Site	Orlando	Florida
United States	Research Site	Philadelphia	Pennsylvania
United States	Research Site	Plano	Texas
United States	Research Site	Portland	Oregon
United States	Research Site	Saint Louis	Missouri
United States	Research Site	San Francisco	California
United States	Research Site	Santa Barbara	California
United States	Research Site	Shirley	New York
United States	Research Site	Silver Spring	Maryland
United States	Research Site	Tacoma	Washington
United States	Research Site	Tigard	Oregon
United States	Research Site	Torrance	California
United States	Research Site	Tyler	Texas
United States	Research Site	West Los Angeles	California
United States	Research Site	Whittier	California

Sponsors (1)

Lead Sponsor	Collaborator
Ambrx, Inc.

Countries where clinical trial is conducted

United States,  Australia,  France,  Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Evaluate Biomarker	To evaluate exploratory blood- and tissue-based biomarkers related to study drug response	2 years
Primary	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	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
Secondary	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
Secondary	Disease control rate (DCR)	DCR is defined as the proportion of complete response (CR), partial response (PR), and stable disease (SD) rates.	2 years
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Trough concentration (Ctrough) for ARX788	Pharmacokinetic parameter trough concentration (Ctrough) for ARX788, ADC, total antibody, and pAF-AS269	Cycle 1 and cycle 3
Secondary	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