Clinical trial NCT05041972: ARX788 in Selected HER2-mutated or HER2-amplified/Overexpressed Solid Tumors (ACE-Pan Tumor-02)
Official title: A Global Phase 2 Study to Evaluate the Efficacy and Safety of ARX788 for Selected HER2-mutated or HER2-amplified/Overexpressed Solid Tumors
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: HER2 Mutation-Related Tumors
HER2 Amplified Solid Tumors
Keywords: HER2 Mutation
HER2 Amplification
Non-Small Cell Lung Cancer (NSCLC)
Colorectal (CRC)
Biliary Tract Cancer (BTC)
Breast Cancer
Other Solid Tumors
Lead sponsor: Ambrx, Inc.
Sponsor class: INDUSTRY
First posted: 2021-09-13
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

Eligibility criteria: 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.

Primary outcomes:
measure: Objective response rate (ORR)
timeFrame: At the end of every 2 cycles (each cycle is 21 days)
Secondary outcomes:
measure: Duration of Response
timeFrame: 1 year
measure: Best Overall Response (BOR)
timeFrame: At the end of every 2 cycles (each cycle is 21 days)
measure: Disease Control Rate (DCR)
timeFrame: 2 years
measure: Progression Free Survival (PFS)
timeFrame: 2 years
measure: Overall Survival (OS)
timeFrame: 2 years
measure: Time to Response (TTR)
timeFrame: At the end of every 2 cycles (each cycle is 21 days)
measure: Maximum serum concentration (Cmax) for ARX788, total antibody, and metabolites
timeFrame: Cycle 1 and Cycle 3
measure: Trough concentration (Ctrough) for ARX788, total antibody, and metabolites
timeFrame: Cycle 1 and Cycle 3
measure: Incidence of anti-drug antibodies (ADAs)
timeFrame: Predose at every cycle (each cycle is 21 days)
Other outcomes:
Locations:
city: Miami Beach
country: United States
facility: Mount Sinai Medical Center
state: Florida
city: Kansas City
country: United States
facility: AMR Kansas City
state: Missouri
Study officials:
affiliation: Ambrx, Inc.
name: Global Trial Lead
role: STUDY_DIRECTOR
References: