Try the modernized beta website. Learn more about the modernization effort.
Working… Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03255070
Recruitment Status : Recruiting
First Posted : August 21, 2017
Last Update Posted : March 11, 2022
Information provided by (Responsible Party):
Ambrx, Inc.

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.

Condition or disease Intervention/treatment Phase
Breast Neoplasms Gastric Neoplasm Solid Tumors Drug: ARX788 Phase 1

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 190 participants
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.

Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : March 20, 2018
Estimated Primary Completion Date : August 2022
Estimated Study Completion Date : March 2023

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
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.
Drug: ARX788
An antibody drug conjugate
Other Name: antibody drug conjugate (ADC)

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.
Drug: ARX788
An antibody drug conjugate
Other Name: antibody drug conjugate (ADC)

Primary Outcome Measures :
  1. 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 ]
    To assess the safety, tolerability, and immunogenicity profile

  2. Phase 1b: Objective response rate (ORR: complete response + partial response) per imaging assessment based on RECIST version 1.1. [ Time Frame: 36 months ]
    Number of subjects with objective response is assessed every 6-8 weeks from Cycle 1 Day 1 through disease progression.

Secondary Outcome Measures :
  1. Number of subjects with tumor response per imaging assessment based on RECIST version 1.1. [ Time Frame: 18 months ]
    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.

  2. Area under the concentration-time curve (AUC) from first infusion to subject end of study. [ Time Frame: 36 months ]
    Pharmacokinetic (PK) characteristics: ARX788 (intact ADC), total mAb, and metabolites

  3. Half-life of ARX788 from first infusion to end of study. [ Time Frame: 36 months ]
    Pharmacokinetic (PK) characteristics: ARX788 from first infusion to subject end of study

  4. Immunogenicity profile of ARX788 [ Time Frame: 36 months ]
    Number of subjects who develop anti-ARX788 antibody

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03255070

Layout table for location contacts
Contact: Trial Inquiry 858-875-2400

Layout table for location information
United States, California
USC Norris Cancer Hospital Recruiting
Los Angeles, California, United States, 90033
Contact: Janice Lu, M.D.         
Principal Investigator: Janice Lu, M.D.         
UCLA Hematology-Oncology Recruiting
Santa Monica, California, United States, 90095
Contact: Sara Hurvitz, M.D.         
Principal Investigator: Sara Hurvitz, M.D.         
United States, Missouri
Washington University School of Medicine Recruiting
Saint Louis, Missouri, United States, 63110
Contact: Haeseong Park, M.D.         
Principal Investigator: Haeseong Park, M.D.         
United States, Ohio
Cleveland Clinic Recruiting
Cleveland, Ohio, United States, 44195
Contact: Thomas Budd, M.D.         
Principal Investigator: Thomas Budd, M.D.         
United States, Texas
Baylor Sammons Cancer Center Recruiting
Dallas, Texas, United States, 75246
Contact: Joyce O'Shaughnessy, M.D.         
Principal Investigator: Joyce O'Shaughnessy, M.D.         
Australia, New South Wales
Albury Wodonga University Hospital Recruiting
East Albury, New South Wales, Australia, 2640
Contact: Richard Eek, M.D.         
Principal Investigator: Richard Eek, M.D.         
Australia, Queensland
Mater Misericordiae Limited Recruiting
South Brisbane, Queensland, Australia, 4101
Contact: Catherine Shannon, M.D.         
Principal Investigator: Catherine Shannon, M.D.         
Princess Alexandria Hospital Recruiting
Woolloongabba, Queensland, Australia, 4102
Contact: Katharine Cuff, M.D.         
Principal Investigator: Katharine Cuff, M.D.         
Australia, Victoria
Monash Health Recruiting
Clayton, Victoria, Australia, 3168
Contact: Sophia Frentzas, M.D.         
Principal Investigator: Sophia Frentzas, M.D.         
Sponsors and Collaborators
Ambrx, Inc.
Layout table for investigator information
Study Director: Ambrx Ambrx, Inc.
Layout table for additonal information
Responsible Party: Ambrx, Inc. Identifier: NCT03255070    
Other Study ID Numbers: ARX788-1711
First Posted: August 21, 2017    Key Record Dates
Last Update Posted: March 11, 2022
Last Verified: February 2022

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Ambrx, Inc.:
antibody drug conjugate
breast cancer
gastric cancer
advanced solid tumors
Additional relevant MeSH terms:
Layout table for MeSH terms
Breast Neoplasms
Stomach Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Gastrointestinal Neoplasms
Digestive System Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Stomach Diseases
Immunologic Factors
Physiological Effects of Drugs