<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03255070</url>
  </required_header>
  <id_info>
    <org_study_id>ARX788-1711</org_study_id>
    <nct_id>NCT03255070</nct_id>
  </id_info>
  <brief_title>A Dose-escalation, Expansion Study of ARX788, in Advanced Solid Tumors Subjects With HER2 Expression (ACE-Pan Tumor 01)</brief_title>
  <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</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Ambrx, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Ambrx, Inc.</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This 2-part, Phase 1, open-label study will determine the recommended Phase 2 dose (RP2D) of&#xD;
      ARX788 in subjects with advanced HER2 positive cancers and will assess the safety and&#xD;
      anticancer activity in breast, gastric and other advanced HER2 positive solid tumors.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Phase 1a will determine the recommended Phase 2 dose (RP2D) in subjects with advanced cancer&#xD;
      whose HER2 test results are in situ hybridization (ISH) positive or immunohistochemistry&#xD;
      (IHC) 3+, based on safety, tolerability, PK findings and antitumor activity. Phase 1b will&#xD;
      assess the safety, tolerability, and PK and anticancer activity in five expansion cohorts,&#xD;
      including breast cancer, gastric cancer / gastroesophageal adenocarcinoma, and other advanced&#xD;
      HER2-positive solid tumors.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">March 20, 2018</start_date>
  <completion_date type="Anticipated">December 2023</completion_date>
  <primary_completion_date type="Anticipated">December 2023</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Sequential Assignment</intervention_model>
    <intervention_model_description>This is a 2-part, Phase 1, open-label study will administer the IMP, ARX788 by IV infusion every 3, 4 or 6 weeks. Sequential dose escalation cohorts are planned using a 3+3 design. A cohort may be expanded to collect additional data if recommended by Safety Monitoring Committee based on comprehensive reviews of safety, tolerability and PK data to determine RP2D.&#xD;
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+.&#xD;
Phase 1b will assess anticancer activity and safety in advanced cancer.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of subjects experiencing adverse events, frequency and seriousness of treatment emergent adverse events (TEAEs)</measure>
    <time_frame>Day 1 through 30 days after last dose</time_frame>
    <description>To assess the safety, tolerability, and immunogenicity profile</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Phase 1b: Objective response rate (ORR: complete response + partial response) per imaging assessment based on RECIST version 1.1.</measure>
    <time_frame>36 months</time_frame>
    <description>Number of subjects with objective response is assessed every 6-8 weeks from Cycle 1 Day 1 through disease progression.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of subjects with tumor response per imaging assessment based on RECIST version 1.1.</measure>
    <time_frame>18 months</time_frame>
    <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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area under the concentration-time curve (AUC) from first infusion to subject end of study.</measure>
    <time_frame>36 months</time_frame>
    <description>Pharmacokinetic (PK) characteristics: ARX788 (intact ADC), total mAb, and metabolites</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Half-life of ARX788 from first infusion to end of study.</measure>
    <time_frame>36 months</time_frame>
    <description>Pharmacokinetic (PK) characteristics: ARX788 from first infusion to subject end of study</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Immunogenicity profile of ARX788</measure>
    <time_frame>36 months</time_frame>
    <description>Number of subjects who develop anti-ARX788 antibody</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">106</enrollment>
  <condition>Breast Neoplasms</condition>
  <condition>Gastric Neoplasm</condition>
  <condition>Solid Tumors</condition>
  <arm_group>
    <arm_group_label>ARX788 Phase 1a (Dose Escalation)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>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.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>ARX788 Phase 1b (Dose Expansion)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>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.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>ARX788</intervention_name>
    <description>An antibody drug conjugate</description>
    <arm_group_label>ARX788 Phase 1a (Dose Escalation)</arm_group_label>
    <arm_group_label>ARX788 Phase 1b (Dose Expansion)</arm_group_label>
    <other_name>antibody drug conjugate (ADC)</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age &gt;18 years&#xD;
&#xD;
          -  Life expectancy &gt;3 months.&#xD;
&#xD;
          -  Female or male subjects whose advanced HER2 expressing cancer has failed standard of&#xD;
             care treatments, or for whom such therapy is not acceptable to the subject. Subjects&#xD;
             with advanced breast, gastric cancer, or other solid tumor who test positive for HER2&#xD;
             by ASCO/CAP criteria (either IHC or FISH) must have received prior treatment with a&#xD;
             trastuzumab containing therapy. Subjects who have been previously treated with&#xD;
             pertuzumab, TDM-1, lapatinib, or other available and accessible HER2-directed&#xD;
             therapies or investigational therapies are eligible.&#xD;
&#xD;
          -  Disease measurability:&#xD;
&#xD;
               -  Phase 1a: measurable or non-measurable disease per RECIST v 1.1.&#xD;
&#xD;
               -  Phase 1b: measurable disease per RECIST v 1.1 (subjects with non-measurable&#xD;
                  disease are not eligible for Phase 1b).&#xD;
&#xD;
          -  Histopathologic evidence of cancer based upon pathology report.&#xD;
&#xD;
          -  Tumor tissue local laboratory HER2 testing results, adequate tumor sample available&#xD;
             for confirmation of HER2 status. Subjects with other types of cancer must have&#xD;
             previously tested locally for HER2 status by HER2 IHC or ISH assay.&#xD;
&#xD;
               -  Phase 1a: ISH positive or IHC 3+ advanced cancer (including breast or&#xD;
                  gastric/esophageal or other solid tumors).&#xD;
&#xD;
               -  Phase 1b: Cohort 8 advanced breast cancer (IHC 3+ or IHC 2+/ISH); Cohort 9&#xD;
                  advanced breast cancer (IHC 2+ / ISH-); Cohort 10 advanced gastric cancer (IHC 3+&#xD;
                  or IHC 2+/ISH+) or gastroesophageal junction adenocarcinoma; Cohort 11 other&#xD;
                  advanced solid tumor cancers with HER2-overexpression (HER2 IHC 3+ or IHC&#xD;
                  2+/IHS+); Cohort 12 advanced solid tumor cancers with HER2 activating mutation.&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group Performance Status of 0 to 1.&#xD;
&#xD;
          -  Acute toxicities from any prior therapy, surgery, or radiotherapy must have resolved&#xD;
             to Grade 0 or 1 as per the NCI-CTCAE v 4.03 (phase 1a) and v 5.0 ( Phase 1b).&#xD;
&#xD;
          -  Adequate organ functions.&#xD;
&#xD;
          -  Willing and able to understand and sign an informed consent inform and to comply with&#xD;
             all aspects of the protocol.&#xD;
&#xD;
          -  Female subjects must be surgically sterile, or have a monogamous partner who is&#xD;
             surgically sterile, or at least 2 years postmenopausal, or who commits to use an&#xD;
             acceptable form of birth control (defined as the use of an intrauterine device, a&#xD;
             barrier method with spermicide, condoms, any form of hormonal contraceptives, or&#xD;
             abstinence) for the duration of the study and for 3 months following the last dose of&#xD;
             study treatment.&#xD;
&#xD;
          -  Male subjects must be sterile (biologically or surgically) or commit to the use of a&#xD;
             reliable method of birth control (condoms with spermicide) for the duration of the&#xD;
             study.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  History of allergic reactions to any component of ARX788.&#xD;
&#xD;
          -  History of ocular events, or any current ongoing active ocular infections.&#xD;
&#xD;
          -  History of congestive heart failure, unstable angina pectoris, unstable atrial&#xD;
             fibrillation, or cardiac arrhythmia within 12 months prior to enrollment&#xD;
&#xD;
          -  Grade 2 to 4 peripheral neuropathy (NCI CTCAE v 5.0)&#xD;
&#xD;
          -  History of unstable central nervous system (CNS) metastases&#xD;
&#xD;
          -  Current severe, uncontrolled systemic disease (eg, clinical significant&#xD;
             cardiovascular, pulmonary, or metabolic diseases)&#xD;
&#xD;
          -  Any uncontrollable intercurrent illness, infection (including subjects with active,&#xD;
             symptomatic Covid-19 infections), or other conditions that could limit study&#xD;
             compliance or interfere with assessments.&#xD;
&#xD;
          -  Exposure to any other investigational or commercial anticancer agents or therapies&#xD;
             administered with the intention to treat malignancy within 14 days before the first&#xD;
             dose of ARX788.&#xD;
&#xD;
          -  Clinically significant surgical intervention (excluding diagnostic biopsy) within 21&#xD;
             days of the first dose of ARX788&#xD;
&#xD;
          -  Radiotherapy administered less than 21 days prior to the first dose of ARX788, or&#xD;
             localized palliative radiotherapy administered less than 7 days prior to the first&#xD;
             dose of ARX788, or radiotherapy-induced toxicity of Grade 2 or greater based on&#xD;
             NCI-CTCAE v 5.0.&#xD;
&#xD;
          -  Pregnancy or breast feeding.&#xD;
&#xD;
          -  Known active HCV, HBV, and/or HIV infection.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Ambrx</last_name>
    <role>Study Director</role>
    <affiliation>Ambrx, Inc.</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>USC Norris Cancer Hospital</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90033</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UCLA Hematology-Oncology</name>
      <address>
        <city>Santa Monica</city>
        <state>California</state>
        <zip>90095</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Washington University School of Medicine</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63110</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cleveland Clinic</name>
      <address>
        <city>Cleveland</city>
        <state>Ohio</state>
        <zip>44195</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Baylor Sammons Cancer Center</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75246</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>East Albury</city>
        <state>New South Wales</state>
        <zip>2640</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>North Sydney</city>
        <state>New South Wales</state>
        <zip>2640</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mater Misericordiae Limited</name>
      <address>
        <city>South Brisbane</city>
        <state>Queensland</state>
        <zip>4101</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Princess Alexandria Hospital</name>
      <address>
        <city>Woolloongabba</city>
        <state>Queensland</state>
        <zip>4102</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Monash Health</name>
      <address>
        <city>Clayton</city>
        <state>Victoria</state>
        <zip>3168</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Frankston</city>
        <state>Victoria</state>
        <zip>3199</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Nedlands</city>
        <state>Western Australia</state>
        <zip>6009</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Australia</country>
    <country>United States</country>
  </location_countries>
  <verification_date>April 2023</verification_date>
  <study_first_submitted>August 14, 2017</study_first_submitted>
  <study_first_submitted_qc>August 16, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 21, 2017</study_first_posted>
  <last_update_submitted>April 6, 2023</last_update_submitted>
  <last_update_submitted_qc>April 6, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">April 10, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>HER2</keyword>
  <keyword>antibody drug conjugate</keyword>
  <keyword>breast cancer</keyword>
  <keyword>gastric cancer</keyword>
  <keyword>advanced solid tumors</keyword>
  <keyword>HER2-overexpression</keyword>
  <keyword>HER2-mutations</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Neoplasms</mesh_term>
    <mesh_term>Breast Neoplasms</mesh_term>
    <mesh_term>Stomach Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Immunoconjugates</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03255070
org study id: ARX788-1711
nct id: NCT03255070
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
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.
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.
allocation: Non-Randomized
intervention model: Sequential Assignment
intervention model description: This is a 2-part, Phase 1, open-label study will administer the IMP, ARX788 by IV infusion every 3, 4 or 6 weeks. Sequential dose escalation cohorts are planned using a 3+3 design. A cohort may be expanded to collect additional data if recommended by Safety Monitoring Committee based on comprehensive reviews of safety, tolerability and PK data to determine RP2D.
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+.
Phase 1b will assess anticancer activity and safety in advanced cancer.
primary purpose: Treatment
masking: None (Open Label)
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
description: To assess the safety, tolerability, and immunogenicity profile
measure: Phase 1b: Objective response rate (ORR: complete response + partial response) per imaging assessment based on RECIST version 1.1.
time frame: 36 months
description: Number of subjects with objective response is assessed every 6-8 weeks from Cycle 1 Day 1 through disease progression.
measure: Number of subjects with tumor response per imaging assessment based on RECIST version 1.1.
time frame: 18 months
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
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
description: Pharmacokinetic (PK) characteristics: ARX788 from first infusion to subject end of study
measure: Immunogenicity profile of ARX788
time frame: 36 months
description: Number of subjects who develop anti-ARX788 antibody
arm group label: ARX788 Phase 1a (Dose Escalation)
arm group type: Experimental
description: 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.
arm group label: ARX788 Phase 1b (Dose Expansion)
arm group type: Experimental
description: 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.
intervention type: Drug
intervention name: ARX788
description: An antibody drug conjugate
arm group label: ARX788 Phase 1a (Dose Escalation)
arm group label: ARX788 Phase 1b (Dose Expansion)
other name: antibody drug conjugate (ADC)
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Ambrx
role: Study Director
affiliation: Ambrx, Inc.
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Australia
country: United States
responsible party type: Sponsor
mesh term: Neoplasms
mesh term: Breast Neoplasms
mesh term: Stomach Neoplasms
mesh term: Immunoconjugates