Study of A166 in Patients With Relapsed/Refractory Cancers Expressing HER2 Antigen or Having Amplified HER2 Gene
HER2-positive Breast Cancer, HER2 Gene Mutation, HER-2 Gene Amplification
About this trial
This is an interventional treatment trial for HER2-positive Breast Cancer
Eligibility Criteria
Inclusion Criteria:
Phase I
Patients must meet the following criteria for inclusion into the study:
- Patients must be able to provide documented voluntary informed consent.
- Male or female patient ≥ 18 years.
- Histologically documented, incurable, locally advanced or metastatic cancer.
- Evaluable or measurable HER2 positive (by ISH or NGS) disease or HER2 expressing disease. HER2 expressing is defined in this protocol as HER2 expression of ≥ 1+ determined by validated IHC.
- Patients should have no available therapy likely to convey clinical benefit.
- Granulocyte count ≥ 1,500/μL, platelet count ≥ 100,000/μL, and hemoglobin ≥ 9 g/dL.
- Serum bilirubin ≤ 1.5 mg/dL, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase ≤ 2.5 × upper limit of normal (ULN), with the exception of patients with hepatic metastases (ALT and AST ≤ 5 × ULN) and patients with hepatic and/or bone metastases (alkaline phosphatase ≤ 5 × ULN).
- Creatinine clearance ≥ 50 mL/min calculated by Cockroft-Gault, Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), or Modification of Diet in Renal Disease (MDRD) formulas. Note that 24 hour urine collection is not required but is allowed.
- ECOG Performance Status ≤ 1.
- Women of childbearing potential and men must agree to use an approved method of birth control (e.g., hormonal, barrier) while receiving study drug, and for at least 7 months after the last dose of study drug. Women are excluded from birth control if they had had tubal ligation or a hysterectomy.
- Patients must have recovered (i.e., improvement to Grade 1 or better) from all acute toxicities from previous therapy, excluding alopecia and vitiligo.
Exclusion Criteria:
Phase I:
- Severe or uncontrolled cardiac disease requiring treatment, congestive heart failure (New York Heart Association) III or IV, unstable angina pectoris even if medically controlled, history of myocardial infarction during the last 6 months, serious arrhythmias requiring medication (with exception of atrial fibrillation or paroxysmal supraventricular tachycardia).
- History of Grade ≥ 3 hypersensitivity reaction to trastuzumab.
- History of any toxicity to trastuzumab that resulted in trastuzumab being permanently discontinued.
- Symptomatic brain metastases or any radiation or surgery for brain metastases within 3 months of first infusion of study drug.
- Require supplemental oxygen for daily activities.
- Documented Grade ≥ 2 peripheral neuropathy.
- Any chemotherapy, hormonal therapy, radiotherapy, immunotherapy, or biologic therapy treatment within 4 weeks of first infusion of study drug.
- Any experimental therapy within 4 weeks of first infusion of study drug.
- Any major surgical procedure within 4 weeks of first infusion of study drug.
- Diagnosed active liver disease, including viral or other hepatitis, current or history of alcoholism, or cirrhosis. Patients who have positive hepatitis B virus test results due to having been previously vaccinated against hepatitis B, as evidenced by negative hepatitis B surface antigen (HBsAg), negative anti hepatitis B core protein, and positive antibody to the HBsAg (anti-HBs) are not excluded.
- Have known prior positive test results for human immunodeficiency virus.
- Uncontrolled hypertension or diabetes.
- Pregnancy or lactation.
- Resting corrected QT interval (QTc) > 470 ms at baseline.
- Left ventricular ejection fraction (LVEF) < 45% determined by echocardiogram (ECHO) or multigated acquisition (MUGA) scan.
- Prior cumulative doxorubicin dose of > 360 mg/m2 or equivalent.
Sites / Locations
- Florida Cancer Specialists & Research Institute
- Beth Israel Deaconess Medical Center Cancer Center
- Karmanos Cancer Institute
- Clinical Research Alliance, Inc.
- Stephenson Cancer Center
- Providence Cancer Institute
- Mary Crowley Cancer Research Centers - Medical City
- The University of Texas MD Anderson Cancer Center
- South Texas Accelerated Research Therapeutics, LLC (START)
- Virginia Cancer Specialist
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Experimental
Experimental
Experimental
Experimental
Experimental
Phase I: Dose Escalation
Phase II: • Cohort 1
Phase II: • Cohort 2
Phase II: • Cohort 3
Phase II: • Cohort 4
Six dose levels have been selected for evaluation in the Phase I part of the study: 0.3, 0.6, 1.2, 2.4, 3.6, and 4.8 mg/kg of A166
HER2 positive (Immunohistochemistry (IHC) 2+ with fluorescence in situ hybridization (FISH) confirmation and Immunohistochemistry (IHC) 3+) breast cancer. Treatment with A166 at recommended Phase II dose.
HER2 positive (Immunohistochemistry (IHC) 2+ with fluorescence in situ hybridization (FISH) confirmation and Immunohistochemistry (IHC) 3+) gastric cancer. Treatment with A166 at recommended Phase II dose.
HER2 low expressing (Immunohistochemistry (IHC) 1+ and IHC 2+ without fluorescence in situ hybridization (FISH) confirmation) breast cancer. Treatment with A166 at recommended Phase II dose.
All cancers other than breast cancer with low HER2 expression (Immunohistochemistry (IHC) 1+ and IHC 2+ without fluorescence in situ hybridization (FISH) confirmation) and HER2 positive (IHC2+ with FISH confirmation and Immunohistochemistry (IHC) 3+) cancers other than breast and gastric cancer. Treatment with A166 at recommended Phase II dose.