Study of A166 in Patients With Relapsed/Refractory Cancers Expressing HER2 Antigen or Having Amplified HER2 Gene
A Phase I-II, FIH Study of A166 in Locally Advanced/Metastatic Solid Tumors Expressing Human Epidermal Growth Factor Receptor 2 (HER2) or Are HER2 Amplified That Did Not Respond or Stopped Responding to Approved Therapies
1 other identifier
interventional
49
1 country
10
Brief Summary
Open-label, Phase I-II, first-in-human (FIH) study for A166 monotherapy in HER2-expressing or amplified patients who progressed on or did not respond to available standard therapies. Patients must have documented HER2 expression or amplification. The patient must have exhausted available standard therapies. Patients will receive study drug as a single IV infusion. Cycles will continue until disease progression or unacceptable toxicity.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_1
Started Jul 2018
Typical duration for phase_1
10 active sites
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
July 6, 2018
CompletedStudy Start
First participant enrolled
July 16, 2018
CompletedFirst Posted
Study publicly available on registry
July 26, 2018
CompletedPrimary Completion
Last participant's last visit for primary outcome
January 12, 2022
CompletedStudy Completion
Last participant's last visit for all outcomes
January 12, 2022
CompletedAugust 3, 2023
August 1, 2023
3.5 years
July 6, 2018
August 2, 2023
Conditions
Outcome Measures
Primary Outcomes (1)
Phase I: Maximum Tolerated Dose
Number of patients with dose limiting toxicities
Minimum of 21 days from date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months
Secondary Outcomes (9)
Phase I: Number of patients with Dose Limiting Toxicities
Minimum of 21 days from date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months
Phase I: Number of participants with treatment-related adverse events as assessed by CTCAE v4.03.
Every 3 weeks from date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months
Phase I: Number of participants who developed measurable anti-drug antibodies
Minimum of 21 days from date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months
Phase I Maximum observed serum or plasma concentration (Cmax).
84 Days from date of first dose
Phase I Clearance (CL).
84 Days from date of first dose
- +4 more secondary outcomes
Study Arms (5)
Phase I: Dose Escalation
EXPERIMENTALSix 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
Phase II: • Cohort 1
EXPERIMENTALHER2 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.
Phase II: • Cohort 2
EXPERIMENTALHER2 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.
Phase II: • Cohort 3
EXPERIMENTALHER2 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.
Phase II: • Cohort 4
EXPERIMENTALAll 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.
Interventions
A166 is an Antibody Drug Conjugate (ADC) targeting HER2 expressing cancer cells.
Eligibility Criteria
You may qualify if:
- Phase I
- 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.
You may not qualify if:
- 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.
- +2 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Klus Pharma Inc.lead
Study Sites (10)
Florida Cancer Specialists & Research Institute
Sarasota, Florida, 34232, United States
Beth Israel Deaconess Medical Center Cancer Center
Boston, Massachusetts, 02215, United States
Karmanos Cancer Institute
Detroit, Michigan, 48201, United States
Clinical Research Alliance, Inc.
Lake Success, New York, 11042, United States
Stephenson Cancer Center
Oklahoma City, Oklahoma, 73104, United States
Providence Cancer Institute
Portland, Oregon, 97213, United States
Mary Crowley Cancer Research Centers - Medical City
Dallas, Texas, 75230, United States
The University of Texas MD Anderson Cancer Center
Houston, Texas, 77030, United States
South Texas Accelerated Research Therapeutics, LLC (START)
San Antonio, Texas, 78229, United States
Virginia Cancer Specialist
Fairfax, Virginia, 22031, United States
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Study Officials
- STUDY CHAIR
Jordi Rodon Ahnert, MD, PhD
MD Anderson
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
July 6, 2018
First Posted
July 26, 2018
Study Start
July 16, 2018
Primary Completion
January 12, 2022
Study Completion
January 12, 2022
Last Updated
August 3, 2023
Record last verified: 2023-08
Data Sharing
- IPD Sharing
- Will not share