HER2 Mutation-Related Tumors, HER2 Amplified Solid Tumors
Conditions
Keywords
HER2 Mutation, HER2 Amplification, Non-Small Cell Lung Cancer (NSCLC), Colorectal (CRC), Biliary Tract Cancer (BTC), Breast Cancer, Other Solid Tumors
Brief summary
A Global Phase 2 Study to Evaluate the Efficacy and Safety of ARX788 for Selected HER2-mutated or HER2-amplified/overexpressed Solid Tumors (ACE-Pan tumor-02)
Detailed description
The study will enroll subjects with HER2-mutated or HER2-amplified/overexpressed 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
Interventions
DRUGARX788
ARX788 will be administered by intravenous (IV) infusion every 3 weeks (Q3W).
Sponsors
Ambrx, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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 Clinical Laboratory Improvement Amendments (CLIA) or equivalent-certified laboratory. * Cohort 1, Cohort 2, and Explanatory Cohort A: HER2 mutated subjects with pre-specified HER2 activating mutation. 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. * Cohort 3: Subjects with HER2 amplifications in biliary tract cancers (BTC) who have not received prior HER2 ADC treatment are eligible. * Cohort 4: Subjects with HER2 amplifications in colorectal cancer (CRC), ovarian, endometrial, NSCLC and other solid tumors who have not received prior HER2 ADC treatment are eligible. * Cohort 5 HER2 mutation or HER2 amplification: subjects with HER2 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. * Subjects with stable brain metastases. * Adequate organ functions.
Exclusion criteria
Any subject who meets any of the following criteria is excluded from the study: * For Cohort 4: breast and gastric/GEJ cancer are excluded. * Prior history of interstitial lung disease, pneumonitis, or other clinically significant lung disease within 12 months. * History of ocular events, any current ongoing active ocular infections, or any chronic corneal disease unless approved by Medical Monitor. * 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. There are additional inclusion and
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective response rate (ORR) | At the end of every 2 cycles (each cycle is 21 days) | The confirmed objective response rate (ORR) of ARX788 by blinded independent central review (BICR) based on RECIST 1.1 in Cohorts 1-5. The ORR is defined as the number of subjects with a best overall response (BOR) of complete response (CR) or partial response (PR) divided by the number of response evaluable subjects |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Best Overall Response (BOR) | At the end of every 2 cycles (each cycle is 21 days) | 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). |
| Disease Control Rate (DCR) | 2 years | DCR is defined as the proportion of complete response (CR), partial response (PR), and stable disease (SD) rates. |
| 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. |
| Overall Survival (OS) | 2 years | Overall survival (OS) is defined as the time from first dose of study therapy to the date of death (any cause). |
| Duration of Response | 1 year | 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. |
| Maximum serum concentration (Cmax) for ARX788, total antibody, and metabolites | Cycle 1 and Cycle 3 | Pharmacokinetic parameter maximum serum concentration (Cmax) for ARX788, total antibody, and metabolites. |
| Trough concentration (Ctrough) for ARX788, total antibody, and metabolites | Cycle 1 and Cycle 3 | Pharmacokinetic parameter trough concentration (Ctrough) for ARX788, total antibody, and metabolites. |
| Incidence of anti-drug antibodies (ADAs) | Predose at every cycle (each cycle is 21 days) | Incidence of anti-drug antibodies (ADAs) following intravenous administration of ARX788 in participants with HER2-mutated or HER2-amplified locally advanced or metastatic solid tumors. |
| Time to Response (TTR) | At the end of every 2 cycles (each cycle is 21 days) | Time to response (TTR) is defined as the time from the start of treatment to the first objective tumor response |
Countries
United States
Outcome results
None listed