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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT03255070




Registration number
NCT03255070
Ethics application status
Date submitted
14/08/2017
Date registered
21/08/2017
Date last updated
1/02/2024

Titles & IDs
Public title
A Dose-escalation, Expansion Study of ARX788, in Advanced Solid Tumors Subjects With HER2 Expression (ACE-Pan Tumor 01)
Scientific title
A Phase 1, Multicenter, Open-label, Multiple Dose-escalation and Expansion Study of ARX788, as Monotherapy in Advanced Solid Tumors With HER2 Expression
Secondary ID [1] 0 0
ARX788-1711
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Breast Neoplasms 0 0
Gastric Neoplasm 0 0
Solid Tumors 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: ARX788 Phase 1a (Dose Escalation) - 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.

Experimental: ARX788 Phase 1b (Dose Expansion) - 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.


Treatment: Drugs: ARX788
An antibody drug conjugate
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of subjects experiencing adverse events, frequency and seriousness of treatment emergent adverse events (TEAEs)
Timepoint [1] 0 0
Day 1 through 30 days after last dose
Primary outcome [2] 0 0
Phase 1b: Objective response rate (ORR: complete response + partial response) per imaging assessment based on RECIST version 1.1.
Timepoint [2] 0 0
36 months
Secondary outcome [1] 0 0
Number of subjects with tumor response per imaging assessment based on RECIST version 1.1.
Timepoint [1] 0 0
18 months
Secondary outcome [2] 0 0
Area under the concentration-time curve (AUC) from first infusion to subject end of study.
Timepoint [2] 0 0
36 months
Secondary outcome [3] 0 0
Half-life of ARX788 from first infusion to end of study.
Timepoint [3] 0 0
36 months
Secondary outcome [4] 0 0
Immunogenicity profile of ARX788
Timepoint [4] 0 0
36 months

Eligibility
Key inclusion criteria
- 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).

- 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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- 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)

- 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.

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
Other
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
20/03/2018
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
18/10/2023
Sample size
Target
Accrual to date
Final
106
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC,WA
Recruitment hospital [1] 0 0
Research Site - East Albury
Recruitment hospital [2] 0 0
Research Site - North Sydney
Recruitment hospital [3] 0 0
Mater Misericordiae Limited - South Brisbane
Recruitment hospital [4] 0 0
Princess Alexandria Hospital - Woolloongabba
Recruitment hospital [5] 0 0
Monash Health - Clayton
Recruitment hospital [6] 0 0
Research Site - Frankston
Recruitment hospital [7] 0 0
Research Site - Nedlands
Recruitment postcode(s) [1] 0 0
2640 - East Albury
Recruitment postcode(s) [2] 0 0
2640 - North Sydney
Recruitment postcode(s) [3] 0 0
4101 - South Brisbane
Recruitment postcode(s) [4] 0 0
4102 - Woolloongabba
Recruitment postcode(s) [5] 0 0
3168 - Clayton
Recruitment postcode(s) [6] 0 0
3199 - Frankston
Recruitment postcode(s) [7] 0 0
6009 - Nedlands
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Missouri
Country [3] 0 0
United States of America
State/province [3] 0 0
Ohio
Country [4] 0 0
United States of America
State/province [4] 0 0
Texas

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Ambrx, Inc.
Address
Country

Ethics approval
Ethics application status

Summary
Brief 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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT03255070
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Ambrx
Address 0 0
Ambrx, Inc.
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