NCT03255070

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.

Trial Health

90
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
106

participants targeted

Target at P75+ for phase_1

Timeline
Completed

Started Mar 2018

Longer than P75 for phase_1

Geographic Reach
2 countries

12 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

August 14, 2017

Completed
7 days until next milestone

First Posted

Study publicly available on registry

August 21, 2017

Completed
7 months until next milestone

Study Start

First participant enrolled

March 20, 2018

Completed
5.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

September 13, 2023

Completed
1 month until next milestone

Study Completion

Last participant's last visit for all outcomes

October 18, 2023

Completed
Last Updated

February 1, 2024

Status Verified

January 1, 2024

Enrollment Period

5.5 years

First QC Date

August 14, 2017

Last Update Submit

January 31, 2024

Conditions

Breast NeoplasmsGastric NeoplasmSolid Tumors

Keywords

HER2antibody drug conjugatebreast cancergastric canceradvanced solid tumorsHER2-overexpressionHER2-mutations

Outcome Measures

Primary Outcomes (2)

  • Number of subjects experiencing adverse events, frequency and seriousness of treatment emergent adverse events (TEAEs)

    To assess the safety, tolerability, and immunogenicity profile

    Day 1 through 30 days after last dose

  • Phase 1b: Objective response rate (ORR: complete response + partial response) per imaging assessment based on RECIST version 1.1.

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

    36 months

Secondary Outcomes (4)

  • Number of subjects with tumor response per imaging assessment based on RECIST version 1.1.

    18 months

  • Area under the concentration-time curve (AUC) from first infusion to subject end of study.

    36 months

  • Half-life of ARX788 from first infusion to end of study.

    36 months

  • Immunogenicity profile of ARX788

    36 months

Study Arms (2)

ARX788 Phase 1a (Dose Escalation)

EXPERIMENTAL

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

ARX788 Phase 1b (Dose Expansion)

EXPERIMENTAL

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

Interventions

ARX788DRUG

An antibody drug conjugate

Also known as: antibody drug conjugate (ADC)
ARX788 Phase 1a (Dose Escalation)ARX788 Phase 1b (Dose Expansion)

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.
  • +1 more criteria

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (12)

USC Norris Cancer Hospital

Los Angeles, California, 90033, United States

Location

UCLA Hematology-Oncology

Santa Monica, California, 90095, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

Baylor Sammons Cancer Center

Dallas, Texas, 75246, United States

Location

Research Site

East Albury, New South Wales, 2640, Australia

Location

Research Site

North Sydney, New South Wales, 2640, Australia

Location

Mater Misericordiae Limited

South Brisbane, Queensland, 4101, Australia

Location

Princess Alexandria Hospital

Woolloongabba, Queensland, 4102, Australia

Location

Monash Health

Clayton, Victoria, 3168, Australia

Location

Research Site

Frankston, Victoria, 3199, Australia

Location

Research Site

Nedlands, Western Australia, 6009, Australia

Location

MeSH Terms

Conditions

Breast NeoplasmsStomach Neoplasms

Interventions

ARX788Immunoconjugates

Condition Hierarchy (Ancestors)

Neoplasms by SiteNeoplasmsBreast DiseasesSkin DiseasesSkin and Connective Tissue DiseasesGastrointestinal NeoplasmsDigestive System NeoplasmsDigestive System DiseasesGastrointestinal DiseasesStomach Diseases

Intervention Hierarchy (Ancestors)

AntibodiesImmunoglobulinsSerum GlobulinsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsGlobulinsImmunologic FactorsPhysiological Effects of DrugsPharmacologic ActionsChemical Actions and Uses

Study Officials

  • Ambrx

    Ambrx, Inc.

    STUDY DIRECTOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
SEQUENTIAL
Model Details: 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.
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

August 14, 2017

First Posted

August 21, 2017

Study Start

March 20, 2018

Primary Completion

September 13, 2023

Study Completion

October 18, 2023

Last Updated

February 1, 2024

Record last verified: 2024-01

Locations

US(5)AU(7)