ARX788 in HER2-positive, Metastatic Breast Cancer Subjects (ACE-Breast-03)
- Registration Number
- NCT04829604
- Lead Sponsor
- Ambrx, Inc.
- 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 71
- 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
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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description ARX788 ARX788 The investigational medicinal product (IMP), ARX788, will be administered every 3 weeks (Q3W) by intravenous (IV) infusion.
- Primary Outcome Measures
Name Time Method Objective response rate (ORR) 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 Outcome Measures
Name Time Method Duration of response (DOR) 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.
Disease control rate (DCR) 2 years DCR is defined as the proportion of complete response (CR), partial response (PR), and stable disease (SD) rates.
Maximum serum concentration (Cmax) for ARX788 Cycle 1 and cycle 3 Pharmacokinetic parameter maximum serum concentration (Cmax) for ARX788, ADC, ADA, total antibody, and pAF-AS269
Best overall response (BOR) 2 years 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)
Overall survival (OS) 2.5 years 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) 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 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.
Trough concentration (Ctrough) for ARX788 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 Cycle 1 and cycle 3 Pharmacokinetic parameter area under the serum concentration-time curve (AUC) for ARX788, ADC, total antibody, and pAF-AS269
Time to response (TTR) Start of treatment to first objective confirmed BOR of CR or PR, assessed for approximately 2 years Time it takes for patient to respond to study treatment
Trial Locations
- Locations (1)
Research Site
🇰🇷Suwon, Korea, Republic of