Clinical Trials /

A Dose-escalation, Expansion Study of ARX788, in Advanced Solid Tumors Subjects With HER2 Expression (ACE-Pan Tumor 01)

NCT03255070

Description:

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.

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

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Dose-escalation, Expansion Study of ARX788, in Advanced Solid Tumors Subjects With HER2 Expression (ACE-Pan Tumor 01)
  • 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

Clinical Trial IDs

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

Conditions

  • Breast Neoplasms
  • Gastric Neoplasm
  • Solid Tumors

Interventions

DrugSynonymsArms
ARX788antibody drug conjugate (ADC)Phase 1a: Cohort 1

Purpose

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.
    

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: Cohort 5ExperimentalCohort 5 will administer Dose Level 3 of ARX788 every 4 weeks (Q4W) via intravenous infusion.
  • ARX788
Phase 1a: Cohort 6ExperimentalCohort 6 will administer Dose Level 4 of ARX788 every 4 weeks (Q4W) via intravenous infusion.
  • ARX788
Phase 1a: Cohort 7ExperimentalCohort 7 will administer Dose Level 5 of ARX788 every 4 weeks (Q4W) via intravenous infusion.
  • ARX788
Phase 1b: Cohort 8 Q6WExperimentalCohort 8 will administer Dose Level 5 of ARX788 every 6 weeks (Q6W) via intravenous infusion.
  • ARX788
Phase 1b: Cohort 9 Q4WExperimentalCohort 9 will administer RP2D of ARX788 every 4 weeks (Q4W) via intravenous infusion in breast cancer subjects.
  • ARX788
Phase 1b: Cohort 10ExperimentalCohort 10 will administer RP2D of ARX788 every 4 weeks (Q4W) via intravenous infusion in gastric cancer subjects.
  • ARX788
Phase 1b: Cohort 11ExperimentalCohort 11 will administer RP2D of ARX788 every 4 weeks (Q4W) via intravenous infusion in advanced solid tumor subjects.
  • ARX788
Phase 1b: Cohort 12ExperimentalCohort 12 will administer RP2D of ARX788 every 4 weeks (Q4W) via intravenous infusion in advanced solid tumor subject with HER2 mutant.
  • ARX788
Phase 1a: Cohort 6bExperimentalCohort 6b will administer Dose Level 4 of ARX788 every 3 weeks (Q3W) via intravenous infusion.
  • ARX788

Eligibility Criteria

        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.

        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.
      
Maximum Eligible Age:N/A
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:To assess the safety, tolerability, and immunogenicity profile

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: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.
Measure:Area under the concentration-time curve (AUC) from first infusion to subject end of study.
Time Frame:36 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:36 months
Safety Issue:
Description:Pharmacokinetic (PK) characteristics: ARX788 from first infusion to subject end of study
Measure:Immunogenicity profile of ARX788
Time Frame:36 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
  • antibody drug conjugate
  • breast cancer
  • gastric cancer
  • advanced solid tumors
  • HER2-overexpression
  • HER2-mutations

Last Updated

March 22, 2021