Clinical Trials /

A Dose-escalation Study of ARX788, IV Administered in Subjects With Advanced Cancers With HER2 Expression

NCT03255070

Description:

This is a 2-part, Phase 1, open-label study. Phase 1a of this study is designed to 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+ and Phase 1b is designed to assess anticancer activity and safety in 2 advanced breast cancer expansion cohorts: 1) for tumors that test as HER2 ISH positive or IHC3+ and, 2) for tumors that test as HER2 ISH negative with IHC 2+.

Related Conditions:
  • Breast Carcinoma
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Dose-escalation Study of ARX788, IV Administered in Subjects With Advanced Cancers With HER2 Expression
  • 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

Clinical Trial IDs

  • ORG STUDY ID: ARX788-1711
  • NCT ID: NCT03255070

Conditions

  • Breast Neoplasms
  • Stomach Neoplasm

Interventions

DrugSynonymsArms
ARX788Phase 1a: Cohort 1

Purpose

This is a 2-part, Phase 1, open-label study. Phase 1a of this study is designed to 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+ and Phase 1b is designed to assess anticancer activity and safety in 2 advanced breast cancer expansion cohorts: 1) for tumors that test as HER2 ISH positive or IHC3+ and, 2) for tumors that test as HER2 ISH negative with IHC 2+.

Trial Arms

NameTypeDescriptionInterventions
Phase 1a: Cohort 1ExperimentalCohort 1 will administer Dose Level 1 of ARX788 every 4 weeks (Q4W) via intravenous infusion.
  • ARX788
Phase 1a: Cohort 2ExperimentalCohort 1 will administer Dose Level 1 of ARX788 every 3 weeks (Q3W) via intravenous infusion.
  • ARX788
Phase 1a: Cohort 3ExperimentalCohort 3 will administer Dose Level 2 of ARX788 every 4 weeks (Q4W) via intravenous infusion.
  • ARX788
Phase 1a: Cohort 4ExperimentalCohort 4 will administer Dose Level 2 of ARX788 every 3 weeks (Q3W) via intravenous infusion.
  • ARX788
Phase 1a: Optional Cohort 5 Q3WExperimentalCohort 5 may administer Dose Level 3 of ARX788 every 3 weeks (Q3W) via intravenous infusion.
  • ARX788

Eligibility Criteria

        Inclusion Criteria:

          -  Age >18 years and ≤75 years.

          -  Life expectancy >12 weeks.

          -  BMI 18 to 32 kg/m2.

          -  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 and gastric cancer 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 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, GE junction or esophageal cancer, where applicable. Subjects with
             other types of cancer must have previously tested 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 1: advanced breast cancer, ISH positive or IHC 3+.

          -  Cohort 2: advanced breast cancer, ISH negative with IHC 2+.

          -  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.

          -  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:

          -  History of allergic reactions to any component of the IMP.

          -  History of interstitial lung disease, pneumonitis or other clinically significant lung
             diseases.

          -  Any CT imaging findings indicating radiation or drug-induced lung disorders at the
             time of screening

          -  Any known clinically significant prior radiation to the chest area that included lung
             parenchyma.

          -  History of ocular events related to keratitis or corneal disorders, or any current
             ongoing active ocular infections.

          -  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. Hormonal therapy may be administered up to 7 days prior to the first
             dose of the IMP.

          -  Clinically 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 administered 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.

          -  Known active HCV, HBV, and/or HIV infection.
      
Maximum Eligible Age:75 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

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
Safety Issue:
Description:Number of subjects with objective response is assessed every 6-8 weeks from Cycle 1 Day 1 through disease progression.

Secondary Outcome Measures

Measure:Number of subjects with tumor response per imaging assessment based on RECIST version 1.1.
Time Frame:18 months
Safety Issue:
Description:
Measure:Area under the concentration-time curve (AUC) from first infusion to subject end of study.
Time Frame:18 months
Safety Issue:
Description:Pharmacokinetic (PK) characteristics: ARX788 (intact ADC), total mAb, and metabolites
Measure:Half-life of ARX788 from first infusion to end of study.
Time Frame:18 months
Safety Issue:
Description:Pharmacokinetic (PK) characteristics: ARX788 from first infusion to subject end of study
Measure:Immunogenicity profile of ARX788
Time Frame:18 months
Safety Issue:
Description:Number of subjects who develop anti-ARX788 antibody

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Ambrx, Inc.

Trial Keywords

  • HER2
  • Breast Cancer
  • ADC
  • antibody drug conjugate
  • elevated HER2 expression
  • breast neoplasm
  • stomach neoplasm
  • gastrointestinal neoplasm
  • digestive system
  • breast diseases
  • digestive system neoplasm
  • digestive system diseases
  • stomach diseases

Last Updated

March 12, 2018