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

• ClinicalTrials.gov Identifier: NCT03255070
• Recruitment Status: Recruiting
• First Posted: August 21, 2017
• Last Update Posted: March 11, 2022
• Sponsor: Ambrx, Inc.
• Information provided by (Responsible Party): Ambrx, Inc.

Study Description

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.

Study Design

• 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

Arms and Interventions

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)

Outcome Measures

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

Eligibility Criteria

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

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.

Contacts and Locations

Contacts

Contact: Trial Inquiry; 858-875-2400; pantumor01trialinquiry@ambrx.com

Locations

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.

Investigators

• Study Director: Ambrx; Ambrx, Inc.

More Information

• Responsible Party: Ambrx, Inc.
• ClinicalTrials.gov Identifier: NCT03255070
• Other Study ID Numbers: ARX788-1711
• First Posted: August 21, 2017
• Last Update Posted: March 11, 2022
• Last Verified: February 2022

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Ambrx, Inc.:

HER2; antibody drug conjugate; breast cancer; gastric cancer; advanced solid tumors; HER2-overexpression; HER2-mutations

Additional relevant MeSH terms:

Neoplasms; Breast Neoplasms; Stomach Neoplasms; Neoplasms by Site; Breast Diseases; Skin Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Immunoconjugates; Immunologic Factors; Physiological Effects of Drugs