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

Ambrx, Inc.0 sites210 target enrollmentDecember 22, 2021

ConditionsMetastatic Breast Cancer Resistant or Refractory MedDRA version: 20.0Level: LLTClassification code 10027475Term: Metastatic breast cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 20.1Level: PTClassification code 10055113Term: Breast cancer metastaticSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]

Overview

Phase: Phase 1
Intervention: Not specified
Conditions: Metastatic Breast Cancer Resistant or Refractory
Sponsor: Ambrx, Inc.
Enrollment: 210
Status: Active, not recruiting
Last Updated: 2 years ago

Overview Investigators Eligibility Criteria Outcomes Similar Trials

Overview

Brief Summary

No summary available.

Registry

who.int

Start Date

December 22, 2021

End Date

TBD

Last Updated

2 years ago

Study Type

Interventional clinical trial of medicinal product

Sex

All

Investigators

Sponsor

Ambrx, Inc.

Eligibility Criteria

Inclusion Criteria

•1\. Age \= 18 years
•2\. Life expectancy \> 3 months.
•3\. ECOG Performance Status \= 1
•4\. Metastatic breast cancer subjected previously treated with T\-DM1, and/or T\-DXd, and/or tucatinib\-containing regimens. Subjects must have been previously treated with one (or more) of these regimens to be eligible. Subjects must have been treated with trastuzumab plus taxane.
•Subjects who received prior pertuzumab, lapatinib, neratinib, margetuximab, and/or other available and accessible HER2\-directed therapies or investigational therapies are eligible.
•5\. Presence of at least one measurable lesion per RECIST v 1\.1 as determined by BICR.
•6\. A tumor block or formalin\-fixed paraffin\-embedded (FFPE) tissue from tumor biopsies as 10 pre\-cut unstained slides must be collected for the HER2 status evaluation and biomarker analysis based on most recent tumor tissue sample. If insufficient tissue, a fresh tumor biopsy must be collected. All tumor tissue (including the pathology report and methods of pathology laboratory's tissue preparation/testing) needs to be sourced for central laboratory for HER2 testing.
•7\. Central laboratory\-confirmed HER2\-positive expression (estrogen receptor/progesterone receptor positive subjects may be enrolled if they are HER2\-positive) according to 2018 American Society of Clinical Oncology – College of American Pathologists (ASCO\-CAP) guidelines. See Laboratory Manual for details.
•8\. Subjects whose brain metastases have been treated may participate provided they show radiographic stability (defined as 1 brain MR image, obtained at least four weeks after treatment to the brain metastases, shows no evidence of intracranial progression). In addition, any neurologic symptoms (including seizures) that developed either as a result of the brain metastases or their treatment must have returned to baseline or resolved. Any steroids administered as part of this therapy must be completed at least three days prior to study medication. After approximately 20 such subjects \[20% of the first 100 subjects] have been enrolled, subsequent subjects with any current or past history of brain metastases will be excluded.
•9\. Acute toxicities from any prior therapy, surgery, or radiotherapy must have resolved to Grade 0 or 1 as per the NCI\-CTCAE v 5\.0, except alopecia.

Exclusion Criteria

•1\. History of allergic reactions to any component of ARX788\.
•2\. Prior history of interstitial lung disease, pneumonitis, or other clinically significant lung disease within 12 months prior to screening, with the exception of that directly attributable to the presence of lung metastases from their underlying cancer. Subjects with significant treatment\-related lung injury, defined as any of the following, will be excluded:
•a) Any prior history of drug\-induced immune\-mediated pneumonitis.
•b) Prior history of radiation therapy to the chest of \> 18 Gy with residual sequelae considered clinically significant by Investigator assessment.
•c) Radiographic evidence of radiation fibrosis involving \> 15% of the lung parenchyma associated with clinical symptoms.
•3\. Any active ocular infections until resolved or any chronic corneal disorder unless approved by Medical Monitor. Keratopathy of grade \=1 due to prior treatment with anti\-HER2 ADC or chemotherapy are allowed.
•4\. History of congestive heart failure, unstable angina pectoris, unstable atrial fibrillation, or cardiac arrhythmia within 12 months prior to enrollment. Medical history of myocardial infarction within 6 months prior to enrollment. Baseline QTc, averaged over 3 screening ECGs must be \= 470 msec (females) or \= 450 msec (males).
•5\. Grade 3 to 4 peripheral neuropathy (NCI\-CTCAE v 5\.0\). Patients with Grade 2 neuropathy can be enrolled at investigator’s discretion.
•6\. Non\-manageable electrolyte imbalances including hypokalemia, hypocalcemia, or hypomagnesemia (Grade 2 or greater based on NCI\-CTCAE v 5\.0\).
•7\. 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.