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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02512237




Registration number
NCT02512237
Ethics application status
Date submitted
22/06/2015
Date registered
30/07/2015
Date last updated
5/06/2020

Titles & IDs
Public title
A Dose-escalation Study of ARX788, IV Administered in Subjects With Advanced Cancers With HER2 Expression
Scientific 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
Secondary ID [1] 0 0
Universal Trial Number (UTN)
Secondary ID [2] 0 0
ZMC-ARX788-101
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Breast Neoplasms 0 0
Stomach Neoplasms 0 0
Condition category
Condition code
Cancer 0 0 0 0
Breast
Cancer 0 0 0 0
Stomach

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - ARX788

Experimental: Phase 1a: Dose-Escalation - 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.

Experimental: Phase 1b: Dose-evaluation 1 - 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.

Experimental: Phase 1b: Dose-evaluation 2 - 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.

Experimental: Phase 1b: Dose-evaluation 3 - 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.


Treatment: Drugs: ARX788
ARX788, an antibody drug conjugate

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Maximum tolerated dose of ARX788 - Determine highest dose level at which less than 2 of 6 subjects experience a dose limiting toxicity.
Timepoint [1] 0 0
12 months
Secondary outcome [1] 0 0
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.
Timepoint [1] 0 0
30 months
Secondary outcome [2] 0 0
Area under the plasma concentration versus time curve (AUC) of ARX788 after infusion - Pharmakokinetic characteristics of ARX788 for infusion Cycle 1 and Cycle 3
Timepoint [2] 0 0
30 months
Secondary outcome [3] 0 0
Half-life of ARX788 after infusion - Pharmakokinetic characteristics of ARX788 for infusion Cycle 1 and Cycle 3
Timepoint [3] 0 0
30 months
Secondary outcome [4] 0 0
Number of participants with tumor response to ARX788 administration
Timepoint [4] 0 0
18 months
Secondary outcome [5] 0 0
Number of subjects developed anti-ARX788 antibody - Immunogenicity profile assessment
Timepoint [5] 0 0
30 months

Eligibility
Key inclusion criteria
1. Life expectancy >12 weeks.

2. BMI is between 18 to 32 kg/m2

3. 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.

4. 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).

5. Histopathologic evidence of breast cancer based upon pathologist's report.

6. 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+.

7. 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.

8. Eastern Cooperative Oncology Group Performance Status of 0 to 1.

9. 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.

10. The last dose of prior anticancer therapy must have been administered at least 28 days
prior to the first dose of the IMP.

11. 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.

12. 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).

13. 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.

14. 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.

15. Willing and able to understand and sign an informed consent inform and to comply with
all aspects of the protocol.

16. 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.

17. 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.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Any subject who meets any of the following criteria should be excluded
from the study:

1. History of allergic reactions to any component of the ARX788.

2. 2. History of seizure disorder.

3. 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.

4. History of congestive heart failure, unstable angina pectoris, unstable atrial
fibrillation, or cardiac arrhythmia.

5. Grade 2 to 4 peripheral neuropathy (NCI CTCAE v 4.03).

6. Non-manageable electrolyte imbalances including hypokalemia, hypocalcemia, or
hypomagnesemia (Grade 2 or greater based on NCI CTCAE v 4.03).

7. Any uncontrollable intercurrent illness, infection, or other conditions that could
limit study compliance or interfere with assessments.

8. 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.

9. Significant surgical intervention within 21 days of the first dose of the IMP or with
ongoing post-operative complications if more than 21 days.

10. 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.

11. Pregnancy or breast feeding.

12. Refusal to use effective methods of contraception (see inclusion criteria for
details).

13. Legal incapacity/limited legal capacity for providing informed consent.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Terminated
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD,VIC
Recruitment hospital [1] 0 0
Mater Adult Hospital - South Brisbane
Recruitment hospital [2] 0 0
Princess Alexandra Hospital - Woolloongabba
Recruitment hospital [3] 0 0
Monash Medical Centre - Clayton
Recruitment hospital [4] 0 0
Epworth Healthcare - Richmond
Recruitment postcode(s) [1] 0 0
4101 - South Brisbane
Recruitment postcode(s) [2] 0 0
4102 - Woolloongabba
Recruitment postcode(s) [3] 0 0
3168 - Clayton
Recruitment postcode(s) [4] 0 0
3121 - Richmond
Recruitment outside Australia
Country [1] 0 0
New Zealand
State/province [1] 0 0
Auckland
Country [2] 0 0
New Zealand
State/province [2] 0 0
Wellington
Country [3] 0 0
New Zealand
State/province [3] 0 0
Christchurch

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Zhejiang Medicine Co., Ltd.
Address
Country
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
Ambrx, Inc.
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief 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) 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+).
Trial website
https://clinicaltrials.gov/show/NCT02512237
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT02512237