ARX788 in Selected HER2-mutated or HER2-amplified Solid Tumors

Status and phase: Not yet enrolling; Phase 2

Conditions: HER2 Amplification; HER2 Mutation-Related Tumors

Study type: Interventional

Funder types: Industry

Identifiers

NCT05023330

ACE-Pan Tumor-02

Details and patient eligibility

About

A Global Phase 2 Study to Evaluate the Efficacy and Safety of ARX788 for Selected HER2-mutated or HER2-amplified Solid Tumors

Full description

The study will enroll subjects with HER2-mutated or HER2-amplified locally advanced or metastatic solid tumor cancers whose prior standard of care therapies have failed. This basket trial will evaluate ARX788 across multiple cancer populations, as defined by HER2 genetic biomarkers.

Enrollment: 250 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

Age ≥ 18 years and older Life expectancy > 3 months Eastern Cooperative Oncology Performance Status ≤ 1 HER2 status must be determined from a local CLIA-certified laboratory. Cohort 1, Cohort 2, and Explanatory Cohort A: HER2 mutation: activating mutation defined as "oncogenic" and/or "gain of function". Mutations must be determined by NGS platform. Subjects with HER2 mutations in NSCLC (Cohort 1), breast cancer (Cohort 2), and other solid tumors (Cohort A) who have not received prior HER2 antibody drug conjugate (ADC) treatment are eligible. Subjects with tumors harboring concurrent HER2 mutation and amplification are excluded from HER2 mutation basket (Cohorts 1, 2, A), but may be considered for enrollment into HER2 amplification (Cohorts 3 and 4) or HER2 ADC pre-treated basket (Cohort 5). Cohort 3 and Cohort 4: HER2 amplification (copy number ≥ 4) on NGS platform or ISH (HER2/CEP17 ratio ≥ 2.0). Subjects with HER2 amplifications in biliary tract cancers (BTC) (Cohort 3), colorectal cancer (CRC), ovarian, endometrial, NSCLC, and other solid tumors (Cohort 4) who have not received prior HER2 ADC treatment are eligible. Breast cancer and gastric/GEJ cancer subjects are not allowed in HER2 amplification cohorts. Cohort 5 HER2 mutation or HER2 amplification: subjects with HER@ mutated or amplified tumors and have been previously treated with HER2 ADC are eligible. Subjects who are resistant or refractory to previous standard care of treatment. Cohorts 1-4 and Explanatory Cohort A must be HER2 ADC treatment naïve. Cohort 5 must have been previously treated with an HER2 ADC. Presence of at least one measurable lesion per RECIST 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 form and to comply with all aspects of the protocol. Male and female subjects of reproductive/childbearing potential must agree to use a highly effective form of contraception or avoid intercourse during and upon completion of the study and for at least 6 months after the last dose of the study drug.

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. For Cohort 4: breast and gastric/GEJ cancer are excluded. Active primary central nervous system tumors and/or leptomeningeal metastases. 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 2 to 4 peripheral neuropathy (NCI CTCAE v 5.0). Non-manageable electrolyte imbalances including hypokalemia, hypocalcemia, or hypomagnesemia (Grade 2 or greater based on NCI-CTCAE v 5.0). 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.