ARX788 in Selected HER2-mutated or HER2-amplified/Overexpressed Solid Tumors (ACE-Pan Tumor-02)

Study Overview
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Brief Summary
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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
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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

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

Conditions
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HER2 Mutation-Related Tumors, HER2 Amplified Solid Tumors

Intervention / Treatment
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* Drug: ARX788


Participation Criteria
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Eligibility Criteria
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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 exclusion criteria. The study center will determine if criteria for participation are met.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1: HER2 Mutated Non-Small Cell Lung Cancer (NSCLC)<br>Intervention: Drug: ARX788 | Drug: ARX788<br>* ARX788 will be administered by intravenous (IV) infusion every 3 weeks (Q3W).<br>* Other names: ADC;|
| Experimental: Cohort 2: HER2 Mutation Breast Cancer<br>Intervention: Drug: ARX788 | Drug: ARX788<br>* ARX788 will be administered by intravenous (IV) infusion every 3 weeks (Q3W).<br>* Other names: ADC;|
| Experimental: Exploratory Cohort A: Other HER2-Mutated tumors<br>Intervention: Drug: ARX788 | Drug: ARX788<br>* ARX788 will be administered by intravenous (IV) infusion every 3 weeks (Q3W).<br>* Other names: ADC;|
| Experimental: Cohort 3: HER2 Amplification Biliary Tract Cancer (BTC)<br>Intervention: Drug: ARX788 | Drug: ARX788<br>* ARX788 will be administered by intravenous (IV) infusion every 3 weeks (Q3W).<br>* Other names: ADC;|
| Experimental: Cohort 4 HER2 Amplification Colorectal (CRC), Ovarian Endometrial, NSCLC, and other solid tumors<br>Intervention: Drug: ARX788 | Drug: ARX788<br>* ARX788 will be administered by intravenous (IV) infusion every 3 weeks (Q3W).<br>* Other names: ADC;|
| Experimental: Cohort 5: HER2 Mutation or HER2 Amplification Solid Tumors<br>Intervention: Drug: ARX788 | Drug: ARX788<br>* ARX788 will be administered by intravenous (IV) infusion every 3 weeks (Q3W).<br>* Other names: ADC;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate (ORR) | 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 | At the end of every 2 cycles (each cycle is 21 days) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of Response | 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. | 1 year | 
| 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). | At the end of every 2 cycles (each cycle is 21 days) | 
| Disease Control Rate (DCR) | DCR is defined as the proportion of complete response (CR), partial response (PR), and stable disease (SD) rates. | 2 years | 
| Progression Free Survival (PFS) | PFS is defined as the time between date of first dose of study therapy and date of progression or death. | 2 years | 
| Overall Survival (OS) | Overall survival (OS) is defined as the time from first dose of study therapy to the date of death (any cause). | 2 years | 
| Time to Response (TTR) | Time to response (TTR) is defined as the time from the start of treatment to the first objective tumor response | At the end of every 2 cycles (each cycle is 21 days) | 
| Maximum serum concentration (Cmax) for ARX788, total antibody, and metabolites | Pharmacokinetic parameter maximum serum concentration (Cmax) for ARX788, total antibody, and metabolites. | Cycle 1 and Cycle 3 | 
| Trough concentration (Ctrough) for ARX788, total antibody, and metabolites | Pharmacokinetic parameter trough concentration (Ctrough) for ARX788, total antibody, and metabolites. | Cycle 1 and Cycle 3 | 
| Incidence of anti-drug antibodies (ADAs) | 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. | Predose at every cycle (each cycle is 21 days) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Non-Small Cell Lung Cancer (NSCLC), Colorectal (CRC), HER2 Mutation, HER2 Amplification, Biliary Tract Cancer (BTC), Breast Cancer, Other Solid Tumors