A Global Phase 2 Study to Evaluate the Efficacy and Safety of ARX788 for Selected HER2-mutated or HER2-amplified/over-expressed Solid Tumors

Study Name
A Global Phase 2 Study to Evaluate the Efficacy and Safety of ARX788 for Selected HER2-mutated or HER2-amplified/over-expressed Solid Tumors
ClinicalTrials.gov Identifier (if applicable)
Clinical Trial Category (check all that apply)
  • Beyond First Line Therapy
  • Targeted Therapy
Study Center
Institution Name
Johns Hopkins University School of Medicine
Institution Address
5255 Loughboro Rd NW
District of Columbia
Zip Code
United States
(202) 660-6500
Study Contacts
Principal Investigator
Michael J. Pishvaian, MD, PhD
P.I. Phone
(202) 660-6500
P.I. Email
Study Coordinator
Michael J. Pishvaian, MD, PhD
Study Coordinator Phone
(202) 660-6500
Study Coordinator Email
Study Contacts
Michael J. Pishvaian, MD, PhD
Johns Hopkins University School of Medicine
5255 Loughboro Rd NW
Washington, DC  20016

Mike Cusnir, MD
Mount Sinai Comprehensive Cancer Center
4306 Alton Road
Miami Beach, FL  33140

OVERVIEW – in layman’s terms (150 words max)
The study will enroll subjects with HER2-mutated or HER2-amplified/over-expressed locally advanced or metastatic solid tumor cancers whose prior standard of care therapies have failed. This trial will evaluate efficacy and safety of ARX788, an anti-HER2 drug conjugate across multiple cancer populations, as defined by HER2 genetic biomarkers.
Study Start Date
Estimated Completion Date
Purpose of the Study – in Layman’s Terms (use the “+” to add more list items)
  • efficacy and safety
  • ARX788
  • antibody drug conjugate
  • HER2
Inclusion Criteria – Patients Must:
  • HER2 mutation
  • HER2 amplification
  • HER2 over-expression:
  • Age ≥ 18 years
  • Life expectancy > 3 months
  • Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of ≤ 1
  • HER2 status must be determined from a local CLIA-certified laboratory (or equivalent)
  • Subjects who are resistant or refractory to previous standard of care treatment
  • Presence of at least one measurable lesion per RECIST 1.1 as determined by BICR
  • A tumor block (preferred) or formalin-fixed paraffin-embedded (FFPE) tissue from most recent tumor biopsies as 10 pre-cut unstained slides must be collected for the HER2 status evaluation and biomarker analysis from most recent, available tumor tissue
  • Subjects whose brain metastases have been treated may participate provided they show radiographic stability (defined as 1 brain MR image, obtained at least four weeks after treatment to the brain metastases, showing no evidence of intracranial progression). In addition, any neurologic symptoms (including seizures) that developed either from the brain metastases or their treatment must have returned to baseline or resolved.
  • Acute toxicities from any prior therapy, surgery, or radiotherapy must have resolved to Grade ≤1 as per the NCI-CTCAE v5.0, except alopecia
  • Adequate bone marrow function defined by absolute neutrophil count of ≥ 1.5 × 109/L, platelet count of ≥ 100.0 × 109/L, and hemoglobin of ≥ 9.0 g/dL
  • Adequate hepatic function, as defined by serum total bilirubin ≤1.5 × ULN, serum aspartate aminotransferase and alanine aminotransferase ≤ 2.5 × ULN. Subjects with known hepatic metastases or primary biliary cancer may have serum total bilirubin ≤ 3.5 × ULN and transaminases ≤ 5 × ULN
  • Adequate renal function defined by serum creatinine ≤ 1.5 × ULN or creatinine clearance ≥ 30 mL/min
  • Adequate cardiac function as assessed by left ventricular ejection fraction (LVEF) ≥ 50% or institutional lower limit of normal; cumulative anthracycline dose < 360 mg/m2 doxorubicin or equivalent
  • Willing and able to understand and sign an informed consent inform and to comply with all aspects of the protocol
  • Male and female subjects of reproductive/childbearing potential must agree to use a highly effective form of contraception or avoid intercourse during and upon completion of the study and for at least 6 months after the last dose of study drug
  • Male subjects must not freeze or donate sperm starting at Screening and throughout the study period, and at least 6 months after the final study drug administration
  • Female subjects must not donate, or retrieve for their own use, ova from the time of Screening and throughout the study treatment period, and for at least 6 months after the final study drug administration
Exclusion Criteria – Patients Must NOT:
  • History of hypersensitivity reactions to any component of ARX788
  • Active primary central nervous system tumors and/or leptomeningeal metastases
  • Prior history of interstitial lung disease, pneumonitis, or other clinically significant lung disease (including asymptomatic radiographic findings) within 12 months prior to screening, with the exception of directly attributable to the presence of lung metastases from their underlying cancer. Subjects with significant treatment-related lung injury, defined as any of the following, will be excluded: a) Any prior history of drug-induced or immune-mediated pneumonitis. b) Prior history of radiation therapy to the chest of > 18 Gy with residual sequelae considered clinically significant by Investigator assessment. c) Radiographic evidence of radiation fibrosis involving > 15% of the lung parenchyma associated with clinical symptoms
  • Any active ocular infections until resolved or any chronic corneal disorder unless approved by Medical Monitor. Keratopathy of grade ≤1 due to prior treatment with anti-HER2 ADC or chemotherapy are allowed
  • History of cardiovascular diseases, including but not limited to congestive heart failure, unstable angina pectoris, unstable atrial fibrillation, uncontrolled cardiac arrhythmia, pulmonary embolism, and/or cerebrovascular accidents within 12 months prior to enrollment
  • Grade 2 to 4 peripheral neuropathy (NCI-CTCAE v5.0)
  • Non-manageable electrolyte imbalances including hypokalemia, hypocalcemia, or hypomagnesemia (Grade 2 or greater based on NCI-CTCAE v5.0)
  • 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. Anti-hormonal therapy may be administered up to 7 days prior to the first dose of ARX788
  • Major surgical intervention within 21 days of the first dose of ARX788 or with ongoing post-operative complications
  • 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 v5.0
  • Pregnancy or breast feeding
  • Known active HCV, HBV, and/or HIV infection. HIV testing is not required for the screening, unless required by the local Health Authorities
  • HER2 ISH, IHC or next generation sequencing
POTENTIAL SIDE-EFFECTS – in layman’s terms
  • Thrombocytopenia
  • Pneumonitis or interstitial lung disease
  • Ocular AEs include dry eye, blurred vision, keratopathy, and keratitis
  • infusion-related reactions include fever, chills, rigors, diaphoresis, and headache
  • Left ventricular dysfunction