Breast NeoplasmsPhase 1NCT03255070
A Dose-escalation, Expansion Study of ARX788, in Advanced Solid Tumors Subjects With HER2 Expression (ACE-Pan Tumor 01)
A Phase 1 study testing ARX788 in people with Breast Neoplasms and Gastric Neoplasm, run by Ambrx, Inc. at 12 sites in 2 countries.
Trial summary
This 2-part, Phase 1, open-label study will determine the recommended Phase 2 dose (RP2D) of ARX788 in subjects with advanced HER2 positive cancers and will assess the safety and anticancer activity in breast, gastric and other advanced HER2 positive solid tumors. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Breast Neoplasms, Gastric Neoplasm, Solid Tumors
- What is being tested?
- ARX788
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 106 participants
- Where
- 12 sitesin 2 countries
- Study dates
- 20 Mar 2018to 18 Oct 2023
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age >18 years
- Life expectancy >3 months.
- Female or male subjects whose advanced HER2 expressing cancer has failed standard of care treatments, or for whom such therapy is not acceptable to the subject. Subjects with advanced breast, gastric cancer, or other solid tumor who test positive for HER2 by ASCO/CAP criteria (either IHC or FISH) must have received prior treatment with a trastuzumab containing therapy. Subjects who have been previously treated with pertuzumab, TDM-1, lapatinib, or other available and accessible HER2-directed therapies or investigational therapies are eligible.
- Disease measurability:
- Phase 1a: measurable or non-measurable disease per RECIST v 1.1.
- Phase 1b: measurable disease per RECIST v 1.1 (subjects with non-measurable disease are not eligible for Phase 1b).
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- Histopathologic evidence of cancer based upon pathology report.
- Tumor tissue local laboratory HER2 testing results, adequate tumor sample available for confirmation of HER2 status. Subjects with other types of cancer must have previously tested locally for HER2 status by HER2 IHC or ISH assay.
- Phase 1a: ISH positive or IHC 3+ advanced cancer (including breast or gastric/esophageal or other solid tumors).
- Phase 1b: Cohort 8 advanced breast cancer (IHC 3+ or IHC 2+/ISH); Cohort 9 advanced breast cancer (IHC 2+ / ISH-); Cohort 10 advanced gastric cancer (IHC 3+ or IHC 2+/ISH+) or gastroesophageal junction adenocarcinoma; Cohort 11 other advanced solid tumor cancers with HER2-overexpression (HER2 IHC 3+ or IHC 2+/IHS+); Cohort 12 advanced solid tumor cancers with HER2 activating mutation.
- Eastern Cooperative Oncology Group Performance Status of 0 to 1.
- Acute toxicities from any prior therapy, surgery, or radiotherapy must have resolved to Grade 0 or 1 as per the NCI-CTCAE v 4.03 (phase 1a) and v 5.0 ( Phase 1b).
- Adequate organ functions.
- Willing and able to understand and sign an informed consent inform and to comply with all aspects of the protocol.
- Female subjects must be surgically sterile, or have a monogamous partner who is surgically sterile, or at least 2 years postmenopausal, or who commits to use an acceptable form of birth control (defined as the use of an intrauterine device, a barrier method with spermicide, condoms, any form of hormonal contraceptives, or abstinence) for the duration of the study and for 3 months following the last dose of study treatment.
- Male subjects must be sterile (biologically or surgically) or commit to the use of a reliable method of birth control (condoms with spermicide) for the duration of the study.
Who cannot join
- History of allergic reactions to any component of ARX788.
- 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)
- History of unstable central nervous system (CNS) metastases
- Current severe, uncontrolled systemic disease (eg, clinical significant cardiovascular, pulmonary, or metabolic diseases)
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- 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.
Trial locations and contacts
12 sites in 2 countries.
12 sites in 2 countries
Australia7 sites
Monash Health
Clayton, Victoria, 3168
Research Site
East Albury, New South Wales, 2640
Research Site
Frankston, Victoria, 3199
Research Site
Nedlands, Western Australia, 6009
Research Site
North Sydney, New South Wales, 2640
Mater Misericordiae Limited
South Brisbane, Queensland, 4101
Princess Alexandria Hospital
Woolloongabba, Queensland, 4102
United States5 sites
Cleveland Clinic
Cleveland, Ohio, 44195
Baylor Sammons Cancer Center
Dallas, Texas, 75246
USC Norris Cancer Hospital
Los Angeles, California, 90033
UCLA Hematology-Oncology
Santa Monica, California, 90095
Washington University School of Medicine
St Louis, Missouri, 63110
About this study
Official title: A Phase 1, Multicenter, Open-label, Multiple Dose-escalation and Expansion Study of ARX788, as Monotherapy in Advanced Solid Tumors With HER2 Expression
This 2-part, Phase 1, open-label study will determine the recommended Phase 2 dose (RP2D) of ARX788 in subjects with advanced HER2 positive cancers and will assess the safety and anticancer activity in breast, gastric and other advanced HER2 positive solid tumors.
Read the detailed description
Phase 1a will determine the recommended Phase 2 dose (RP2D) in subjects with advanced cancer whose HER2 test results are in situ hybridization (ISH) positive or immunohistochemistry (IHC) 3+, based on safety, tolerability, PK findings and antitumor activity. Phase 1b will assess the safety, tolerability, and PK and anticancer activity in five expansion cohorts, including breast cancer, gastric cancer / gastroesophageal adenocarcinoma, and other advanced HER2-positive solid tumors.
- Conditions
- Breast Neoplasms, Gastric Neoplasm, Solid Tumors
- Being tested
- ARX788
- Keywords
- HER2, antibody drug conjugate, breast cancer, gastric cancer, advanced solid tumors, HER2-overexpression, HER2-mutations
- Medical subject headings
- Breast Neoplasms, Stomach Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ARX788Drug
Also called antibody drug conjugate (ADC)
An antibody drug conjugate
| Study group | Role | What they receive |
|---|---|---|
| ARX788 Phase 1a (Dose Escalation) | Experimental | ARX788 will be administered every 3 weeks (Q3W) or every 4 weeks (Q4W) via intravenous (IV) infusion. Patients will be enrolled into escalating dose levels during Dose Escalation period. Receives: Drug: ARX788 |
| ARX788 Phase 1b (Dose Expansion) | Experimental | ARX788 will be administered every 3 weeks (Q3W) via intravenous (IV) infusion. Patients will receive the maximum tolerated dose during the Dose Expansion period of the study. Receives: Drug: ARX788 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of subjects experiencing adverse events, frequency and seriousness of treatment emergent adverse events (TEAEs)
To assess the safety, tolerability, and immunogenicity profile
Measured: Day 1 through 30 days after last dose
Phase 1b: Objective response rate (ORR: complete response + partial response) per imaging assessment based on RECIST version 1.1.
Number of subjects with objective response is assessed every 6-8 weeks from Cycle 1 Day 1 through disease progression.
Measured: 36 months
Secondary outcomes (4)
Number of subjects with tumor response per imaging assessment based on RECIST version 1.1.
The objective response rate (ORR: CR+PR) based on RECIST v1.1 will be assessed as the primary endpoint to determine the anticancer activity of ARX788 as well as best overall response.
Measured: 18 months
Area under the concentration-time curve (AUC) from first infusion to subject end of study.
Pharmacokinetic (PK) characteristics: ARX788 (intact ADC), total mAb, and metabolites
Measured: 36 months
Half-life of ARX788 from first infusion to end of study.
Pharmacokinetic (PK) characteristics: ARX788 from first infusion to subject end of study
Measured: 36 months
Immunogenicity profile of ARX788
Number of subjects who develop anti-ARX788 antibody
Measured: 36 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Aug 2017
- Study start20 Mar 2018
- Primary completion13 Sep 2023
- Study completion18 Oct 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Breast NeoplasmsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Model description
- This is a 2-part, Phase 1, open-label study will administer the IMP, ARX788 by IV infusion every 3, 4 or 6 weeks. Sequential dose escalation cohorts are planned using a 3+3 design. A cohort may be expanded to collect additional data if recommended by Safety Monitoring Committee based on comprehensive reviews of safety, tolerability and PK data to determine RP2D. Phase 1a will determine the recommended Phase 2 dose (RP2D) in subjects with advanced cancer whose HER2 test results are in situ hybridization (ISH) positive or immunohistochemistry (IHC) 3+. Phase 1b will assess anticancer activity and safety in advanced cancer.
- Masking
- None (open label)
- Enrolment
- 106 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ambrx, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Ambrx, Study director, Ambrx, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03255070
- Sponsor's protocol ID
- ARX788-1711
- Status last verified
- Jan 2024
- First submitted
- 14 Aug 2017
- Last updated
- 1 Feb 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 Feb 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1, Multicenter, Open-label, Multiple Dose-escalation and Expansion Study of ARX788, as Monotherapy in Advanced Solid Tumors With HER2 Expression
- ClinicalTrials.gov ID
- NCT03255070
- Acronym / sponsor ID
- ARX788-1711
- Conditions
- Breast Neoplasms, Gastric Neoplasm, Solid Tumors
- Keywords
- HER2, antibody drug conjugate, breast cancer, gastric cancer, advanced solid tumors, HER2-overexpression, HER2-mutations
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 106 participants (actual)
- Lead sponsor
- Ambrx, Inc.Industry (pharma, biotech, devices)
- Study start
- 20 Mar 2018 (actual)
- Primary completion
- 13 Sep 2023 (actual)
- Study completion
- 18 Oct 2023 (actual)
- First posted
- 21 Aug 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This 2-part, Phase 1, open-label study will determine the recommended Phase 2 dose (RP2D) of ARX788 in subjects with advanced HER2 positive cancers and will assess the safety and anticancer activity in breast, gastric and other advanced HER2 positive solid tumors.
Detailed description
Phase 1a will determine the recommended Phase 2 dose (RP2D) in subjects with advanced cancer whose HER2 test results are in situ hybridization (ISH) positive or immunohistochemistry (IHC) 3+, based on safety, tolerability, PK findings and antitumor activity. Phase 1b will assess the safety, tolerability, and PK and anticancer activity in five expansion cohorts, including breast cancer, gastric cancer / gastroesophageal adenocarcinoma, and other advanced HER2-positive solid tumors.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- This is a 2-part, Phase 1, open-label study will administer the IMP, ARX788 by IV infusion every 3, 4 or 6 weeks. Sequential dose escalation cohorts are planned using a 3+3 design. A cohort may be expanded to collect additional data if recommended by Safety Monitoring Committee based on comprehensive reviews of safety, tolerability and PK data to determine RP2D. Phase 1a will determine the recommended Phase 2 dose (RP2D) in subjects with advanced cancer whose HER2 test results are in situ hybridization (ISH) positive or immunohistochemistry (IHC) 3+. Phase 1b will assess anticancer activity and safety in advanced cancer.
| Arm | Type | Receives |
|---|---|---|
| ARX788 Phase 1a (Dose Escalation) | Experimental | Drug: ARX788ARX788 will be administered every 3 weeks (Q3W) or every 4 weeks (Q4W) via intravenous (IV) infusion. Patients will be enrolled into escalating dose levels during Dose Escalation period. |
| ARX788 Phase 1b (Dose Expansion) | Experimental | Drug: ARX788ARX788 will be administered every 3 weeks (Q3W) via intravenous (IV) infusion. Patients will receive the maximum tolerated dose during the Dose Expansion period of the study. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- Age >18 years
- Life expectancy >3 months.
- Female or male subjects whose advanced HER2 expressing cancer has failed standard of care treatments, or for whom such therapy is not acceptable to the subject. Subjects with advanced breast, gastric cancer, or other solid tumor who test positive for HER2 by ASCO/CAP criteria (either IHC or FISH) must have received prior treatment with a trastuzumab containing therapy. Subjects who have been previously treated with pertuzumab, TDM-1, lapatinib, or other available and accessible HER2-directed therapies or investigational therapies are eligible.
- Disease measurability:
- Histopathologic evidence of cancer based upon pathology report.
Key exclusion criteria (12 listed)
- History of allergic reactions to any component of ARX788.
- 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)
- History of unstable central nervous system (CNS) metastases
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ARX788Also: antibody drug conjugate (ADC)An antibody drug conjugate | Drug | ARX788 Phase 1a (Dose Escalation), ARX788 Phase 1b (Dose Expansion) |
Primary outcome
Number of subjects experiencing adverse events, frequency and seriousness of treatment emergent adverse events (TEAEs)
Time frame: Day 1 through 30 days after last dose
To assess the safety, tolerability, and immunogenicity profile
Phase 1b: Objective response rate (ORR: complete response + partial response) per imaging assessment based on RECIST version 1.1.
Time frame: 36 months
Number of subjects with objective response is assessed every 6-8 weeks from Cycle 1 Day 1 through disease progression.
4 secondary outcomes
Number of subjects with tumor response per imaging assessment based on RECIST version 1.1.
Time frame: 18 months
Area under the concentration-time curve (AUC) from first infusion to subject end of study.
Time frame: 36 months
Half-life of ARX788 from first infusion to end of study.
Time frame: 36 months
Immunogenicity profile of ARX788
Time frame: 36 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Feb 2024.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ambrx study director
Ambrx, Inc.
12 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing ARX788 in people with Breast Neoplasms and Gastric Neoplasm, run by Ambrx, Inc. at 12 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 16 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 1 Feb 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 12 sites in Australia, United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of subjects experiencing adverse events, frequency and seriousness of treatment emergent adverse events (TEAEs) (time frame: Day 1 through 30 days after last dose). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Feb 2024.