Breast NeoplasmsPhase 1NCT02512237
A Dose-escalation Study of ARX788, IV Administered in Subjects With Advanced Cancers With HER2 Expression
A Phase 1 study testing ARX788 in people with Breast Neoplasms and Stomach Neoplasms, run by Zhejiang Medicine Co., Ltd. at 7 sites in 2 countries.
Trial summary
This is a 2-part, Phase 1 FIH study with Phase 1a designed to determine the maximum tolerated dose (MTD)/recommended Phase 2 dose (RP2D) in subjects with metastatic cancers with a human epidermal growth factor receptor 2 (HER2) test result that is in situ hybridization (ISH) positive (+) or immunohistochemistry (IHC)… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Breast Neoplasms, Stomach Neoplasms
- 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
- 9 participants
- Where
- 7 sitesin 2 countries
- Study dates
- Mar 2016to Jan 2017
- 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
- Life expectancy >12 weeks.
- BMI is between 18 to 32 kg/m2
- Subjects whose advanced cancer has failed treatment or whose cancer has progressed following available standard therapy or for whom such therapy is not acceptable to the subject. Subjects whose tumor tissue local laboratory results are HER2 ISH positive or IHC3+ must have been previously treated with a HER2 targeting therapy (e.g. trastuzumab, in the country or region where such therapies are available and part of standard of care), or have failed SOC therapy. Subjects who have been previously treated with a HER2 targeting therapy such as trastuzumab or ado-trastuzumab emtansine are eligible.
- Disease measurability: Phase 1a: measureable or non-measureable disease; Phase 1b: disease must be measureable (per RECIST v1.1) (subjects with non-measureable disease are not eligible for Phase 1b).
- Histopathologic evidence of breast cancer based upon pathologist's report.
- Tumor tissue local laboratory HER2 testing results (clinical pathology report) based on FDA or other regulatory agency approved, validated or commercially available IHC or ISH HER2 assay. Pre-screening for HER2 is allowed only for subjects with breast and gastric cancer, where applicable. Subjects with other types of cancer must have previously tested for HER2 status by HER2 IHC or ISH assay. 1) Phase 1a: ISH positive or IHC 2+ or 3+. 2) Phase 1b: Cohort 1: advanced breast cancer, ISH positive or IHC 3+; Cohort 2: advanced breast cancer, ISH negative with IHC 2+; and Cohort 3: advanced gastric cancer, ISH positive or IHC 3+.
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- Local pathology laboratory determination of HER2 status will be accepted, provided that the local laboratory is an accredited site for HER2 testing. In Phase 1b, if the local laboratory was not accredited at the time of testing, an adequate tumor tissue sample is required for central pathology laboratory HER2 testing. The tissue sample may be provided as 10 pre-cut unstained slides or a tumor block.
- 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.
- The last dose of prior anticancer therapy must have been administered at least 28 days prior to the first dose of the IMP.
- Adequate bone marrow function defined by absolute neutrophil count of ≥1.5×109/L, platelet count of ≥100.0×109/L, and hemoglobin of ≥9.0 g/dL.
- Adequate hepatic function defined by serum total bilirubin ≤1.5 × upper limit of normal (ULN), aspartate aminotransferase/alanine aminotransferase ≤2.5 × ULN (or ≤5 × ULN in subjects with liver metastases).
- Adequate renal function assessed by serum creatinine within reference lab normal limits and creatinine clearance (by Chronic Kidney Disease Epidemiology [CKD-EPI] Collaboration equation) ≥60 mL/min.
- Adequate cardiac function as assessed by cardiac troponin I within normal range; left ventricular ejection fraction ≥ 50% or institutional lower limit of normal; cumulative anthracycline dose <360 mg/m2 doxorubicin or equivalent.
- 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.
- Exclusion Criteria: Any subject who meets any of the following criteria should be excluded from the study:
- History of allergic reactions to any component of the ARX788.
- 2. History of seizure disorder.
- History of unstable central nervous system (CNS) metastases or seizure disorder related to the malignancy; however, those subjects who were treated for prior CNS metastases and who are asymptomatic may participate in the study as long as they are not receiving treatment with steroids.
- History of congestive heart failure, unstable angina pectoris, unstable atrial fibrillation, or cardiac arrhythmia.
- Grade 2 to 4 peripheral neuropathy (NCI CTCAE v 4.03).
- Non-manageable electrolyte imbalances including hypokalemia, hypocalcemia, or hypomagnesemia (Grade 2 or greater based on NCI CTCAE v 4.03).
- Any uncontrollable intercurrent illness, infection, 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 28 days before the first dose of the IMP.
- Significant surgical intervention within 21 days of the first dose of the IMP or with ongoing post-operative complications if more than 21 days.
- Radiotherapy administrated less than 21 days prior to the first dose of the IMP, or localized palliative radiotherapy administered less than 7 days prior to the first dose of the IMP, or radiotherapy induced toxicity of Grade 2 or greater based on NCI CTCAE v 4.03.
- Pregnancy or breast feeding.
- Refusal to use effective methods of contraception (see inclusion criteria for details).
- Legal incapacity/limited legal capacity for providing informed consent.
Who cannot join
None listed.
Trial locations and contacts
7 sites in 2 countries.
7 sites in 2 countries
Australia4 sites
Monash Medical Centre
Clayton, Victoria, 3168
Epworth Healthcare
Richmond, Victoria, 3121
Mater Adult Hospital
South Brisbane, Queensland, 4101
Princess Alexandra Hospital
Woolloongabba, Queensland, 4102
New Zealand3 sites
Christchurch Hospital
Christchurch, 8140
Auckland City Hospital
Grafton, Auckland, 1023
Wellington Hospital
Newtown, Wellington Region, 6022
About this study
Official title: A Phase 1, Multicenter, Open-label, Multiple Dose-escalation Study of ARX788, Intravenously Administered as a Single Agent in Subjects With Advanced Cancers With HER2 Expression
This is a 2-part, Phase 1 FIH study with Phase 1a designed to determine the maximum tolerated dose (MTD)/recommended Phase 2 dose (RP2D) in subjects with metastatic cancers with a human epidermal growth factor receptor 2 (HER2) test result that is in situ hybridization (ISH) positive (+) or immunohistochemistry (IHC) 3+ or 2+, and Phase 1b designed to assess anticancer activity and safety in three expansion cohorts: two different advanced breast cancer expansion cohorts (namely, for tumors that test as HER2 ISH positive or IHC3+ and for tumors that test as HER2 ISH negative with IHC 2+), and one advanced gastric cancer expansion cohort (for tumors that test as HER2 ISH positive or IHC3+).
- Conditions
- Breast Neoplasms, Stomach Neoplasms
- Being tested
- ARX788
- Keywords
- HER2, breast cancer, ADC, antibody drug conjugate, elevated HER2 expression
- 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
ARX788, an antibody drug conjugate
| Study group | Role | What they receive |
|---|---|---|
| Phase 1a: Dose-Escalation | Experimental | Six cohorts with escalated dose levels of ARX788 at 0.33 mg/kg, 0.66 mg/kg, 1.3 mg/kg, 2.2 mg/kg, 2.9 mg/kg and 3.8 mg/kg will be administered every 3 weeks via intravenous infusion to determine the MTD. Receives: Drug: ARX788 |
| Phase 1b: Dose-evaluation 1 | Experimental | Breast cancer subjects with high HER2 expression, categorized as ISH positive or IHC3+, will be administered with ARX788 at MTD every 3 weeks via intravenous infusion. Receives: Drug: ARX788 |
| Phase 1b: Dose-evaluation 2 | Experimental | Breast cancer subjects with mid/low HER2 expression, categorized as ISH negative AND IHC2+, will be administered with ARX788 at MTD every 3 weeks via intravenous infusion. Receives: Drug: ARX788 |
| Phase 1b: Dose-evaluation 3 | Experimental | Gastric cancer subjects with high HER2 expression, categorized as ISH positive or IHC3+, will be administered with ARX788 at MTD every 3 weeks via intravenous infusion. Receives: Drug: ARX788 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum tolerated dose of ARX788
Determine highest dose level at which less than 2 of 6 subjects experience a dose limiting toxicity.
Measured: 12 months
Secondary outcomes (5)
Number of subjects with Adverse Events
Safety and tolerability of ARX788 as measured by all adverse events, hematology, blood chemistry, vital signs, electrocardiogram, and physical exam.
Measured: 30 months
Area under the plasma concentration versus time curve (AUC) of ARX788 after infusion
Pharmakokinetic characteristics of ARX788 for infusion Cycle 1 and Cycle 3
Measured: 30 months
Half-life of ARX788 after infusion
Pharmakokinetic characteristics of ARX788 for infusion Cycle 1 and Cycle 3
Measured: 30 months
Number of participants with tumor response to ARX788 administration
Measured: 18 months
Number of subjects developed anti-ARX788 antibody
Immunogenicity profile assessment
Measured: 30 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jul 2015 (estimated)
- Study startMar 2016
- Primary completionJan 2017
- Study completionJan 2017
Why it stopped: Replace with a new trial
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
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 9 participants (actual)
Sponsor and investigators
- Lead sponsor
- Zhejiang Medicine Co., Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Ambrx, Inc.
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02512237
- Sponsor's protocol ID
- ZMC-ARX788-101
- Other IDs
- Universal Trial Number (UTN)
- Status last verified
- Jun 2020
- First submitted
- 22 Jun 2015
- Last updated
- 5 Jun 2020
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Jun 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1, Multicenter, Open-label, Multiple Dose-escalation Study of ARX788, Intravenously Administered as a Single Agent in Subjects With Advanced Cancers With HER2 Expression
- ClinicalTrials.gov ID
- NCT02512237
- Acronym / sponsor ID
- ZMC-ARX788-101
- Conditions
- Breast Neoplasms, Stomach Neoplasms
- Keywords
- HER2, breast cancer, ADC, antibody drug conjugate, elevated HER2 expression
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Replace with a new trial
- Enrolment
- 9 participants (actual)
- Lead sponsor
- Zhejiang Medicine Co., Ltd.Industry (pharma, biotech, devices)
- Collaborators
- Ambrx, Inc.
- Study start
- Mar 2016 (actual)
- Primary completion
- Jan 2017 (actual)
- Study completion
- Jan 2017 (actual)
- First posted
- 30 Jul 2015 (estimated)
- 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 is a 2-part, Phase 1 FIH study with Phase 1a designed to determine the maximum tolerated dose (MTD)/recommended Phase 2 dose (RP2D) in subjects with metastatic cancers with a human epidermal growth factor receptor 2 (HER2) test result that is in situ hybridization (ISH) positive (+) or immunohistochemistry (IHC) 3+ or 2+, and Phase 1b designed to assess anticancer activity and safety in three expansion cohorts: two different advanced breast cancer expansion cohorts (namely, for tumors that test as HER2 ISH positive or IHC3+ and for tumors that test as HER2 ISH negative with IHC 2+), and one advanced gastric cancer expansion cohort (for tumors that test as HER2 ISH positive or IHC3+).
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Phase 1a: Dose-Escalation | Experimental | Drug: ARX788Six cohorts with escalated dose levels of ARX788 at 0.33 mg/kg, 0.66 mg/kg, 1.3 mg/kg, 2.2 mg/kg, 2.9 mg/kg and 3.8 mg/kg will be administered every 3 weeks via intravenous infusion to determine the MTD. |
| Phase 1b: Dose-evaluation 1 | Experimental | Drug: ARX788Breast cancer subjects with high HER2 expression, categorized as ISH positive or IHC3+, will be administered with ARX788 at MTD every 3 weeks via intravenous infusion. |
| Phase 1b: Dose-evaluation 2 | Experimental | Drug: ARX788Breast cancer subjects with mid/low HER2 expression, categorized as ISH negative AND IHC2+, will be administered with ARX788 at MTD every 3 weeks via intravenous infusion. |
| Phase 1b: Dose-evaluation 3 | Experimental | Drug: ARX788Gastric cancer subjects with high HER2 expression, categorized as ISH positive or IHC3+, will be administered with ARX788 at MTD every 3 weeks via intravenous infusion. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (31 listed)
- Life expectancy >12 weeks.
- BMI is between 18 to 32 kg/m2
- Subjects whose advanced cancer has failed treatment or whose cancer has progressed following available standard therapy or for whom such therapy is not acceptable to the subject. Subjects whose tumor tissue local laboratory results are HER2 ISH positive or IHC3+ must have been previously treated with a HER2 targeting therapy (e.g. trastuzumab, in the country or region where such therapies are available and part of standard of care), or have failed SOC therapy. Subjects who have been previously treated with a HER2 targeting therapy such as trastuzumab or ado-trastuzumab emtansine are eligible.
- Disease measurability: Phase 1a: measureable or non-measureable disease; Phase 1b: disease must be measureable (per RECIST v1.1) (subjects with non-measureable disease are not eligible for Phase 1b).
- Histopathologic evidence of breast cancer based upon pathologist's report.
Key exclusion criteria (0 listed)
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 |
|---|---|---|
| ARX788ARX788, an antibody drug conjugate | Drug | Phase 1a: Dose-Escalation, Phase 1b: Dose-evaluation 1, Phase 1b: Dose-evaluation 2, Phase 1b: Dose-evaluation 3 |
Primary outcome
Maximum tolerated dose of ARX788
Time frame: 12 months
Determine highest dose level at which less than 2 of 6 subjects experience a dose limiting toxicity.
5 secondary outcomes
Number of subjects with Adverse Events
Time frame: 30 months
Area under the plasma concentration versus time curve (AUC) of ARX788 after infusion
Time frame: 30 months
Half-life of ARX788 after infusion
Time frame: 30 months
Number of participants with tumor response to ARX788 administration
Time frame: 18 months
Number of subjects developed anti-ARX788 antibody
Time frame: 30 months
Results and safety
The study was stopped early (reason given: Replace with a new trial). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Jun 2020.
- Individual participant dataSharing planned: No
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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.
The record lists no contact. Use the official record to reach the sponsor.
7 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 Stomach Neoplasms, run by Zhejiang Medicine Co., Ltd. at 7 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 31 inclusion and 0 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: stopped early, as of the sponsor's last update on 5 Jun 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in Australia, New Zealand. 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 was stopped early (reason given: Replace with a new trial). Results are not available in the source record.
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?
Maximum tolerated dose of ARX788 (time frame: 12 months). 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 5 Jun 2020.