Phase I/II Study of U3-1402 in Subjects With Human Epidermal Growth Factor Receptor 3 (HER3) Positive Metastatic Breast Cancer
- Registration Number
- NCT02980341
- Lead Sponsor
- Daiichi Sankyo Co., Ltd.
- Brief Summary
This is an open-label, three-part, multiple-dose study to evaluate safety, tolerability, and efficacy of U3-1402 in patients with HER3-positive metastatic breast cancer. HER3 is a unique member of the human epidermal growth factor receptor, which defines a certain type of cancer.
The number of patients and treatment cycles are not fixed in this study. Subjects who continue to derive clinical benefit from the study treatment in the absence of withdrawal of consent, progressive disease (PD), unacceptable toxicity, or death may continue the study treatment until the end of the trial.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 182
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Is 18 Years and older in the United States or 20 Years and older in Japan
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Has a pathologically documented advanced/unresectable or metastatic breast cancer
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Documented HER3-positive disease measured by immunohistochemistry (IHC)
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Has disease that is refractory to or intolerable with standard treatment, or for which standard treatment no longer is available
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Has an Eastern Cooperative Oncology Group Performance Status 0-1
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Has Left Ventricular Ejection Fraction ≥ 50%
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Has measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
Additional Inclusion Criteria for Dose Finding Part and Dose Expansion Part:
-
Has received 2-6 prior chemotherapy regimens for breast cancer, at least 2 of which were administered for treatment of advanced/unresectable or metastatic disease. At least 1 prior chemotherapeutic regimen must have included a taxane, administered in the neoadjuvant, adjuvant, or advanced setting. (With exception of Dose Expansion Part TNBC cohort. See additional inclusion criteria for Dose Expansion Part TNBC cohort.)
Additional Inclusion Criteria for Dose Expansion Part Only:
-
Is able to submit a fresh tumor biopsy sample prior to starting study treatment if not already submitted for HER3 expression
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Has documented hormone (estrogen and/or progesterone) receptor (HR)-positive and HER2 negative expression according to American Society of Clinical Oncology - College of American Pathologists (ASCO-CAP) guidelines. (With exception of Dose Expansion Part TNBC cohort. See additional inclusion criteria for Dose Expansion Part TNBC cohort.)
Additional Inclusion Criteria for Dose Expansion Part TNBC cohort Only:
-
Has documented hormone (estrogen and progesterone) receptor (HR)-negative and HER2 negative expression according to American Society of Clinical Oncology - College of American Pathologists (ASCO-CAP) guidelines
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Has progressed after receiving 1 to 2 prior chemotherapy regimens for advanced/unresectable or metastatic breast cancer.
Key
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Prior treatment with a HER3 antibody
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Prior treatment with an antibody-drug conjugate (ADC) which consists of an exatecan derivative that is a topoisomerase I inhibitor (eg, DS-8201)
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Has a medical history of symptomatic congestive heart failure (New York Heart Association classes II-IV) or serious cardiac arrhythmia requiring treatment
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Has a medical history of myocardial infarction or unstable angina
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Has a corrected QT prolongation to > 450 millisecond (ms) in males and > 470 ms in females
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Has a medical history of clinically significant lung diseases (eg, interstitial pneumonia, pneumonitis, pulmonary fibrosis, and radiation pneumonitis) or who are suspected to have these diseases by imaging at screening period
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Has clinically significant corneal disease
Additional Exclusion Criteria for Dose Expansion Part:
-
Prior treatment with an govitecan derivative (eg, IMMU-132).
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Dose Expansion Part Patritumab Deruxtecan Participants with HER3 high, HER2 negative, HR positive status receive 4.8 mg/kg or 6.4 mg/kg of U3-1402 administered via intravenous (IV) solution at 3-week intervals. Participants with HER3 low, HER2 negative, HR positive status receive 6.4 mg/kg of U3-1402 administered via intravenous (IV) solution at 3-week intervals. Participants with HER3 high, HER2 negative, HR negative status receive 6.4 mg/kg of U3-1402 administration via intravenous (IV) solution at 3-week intervals. Dose Escalation Part Patritumab Deruxtecan Participants receive U3-1402 from 1.6 mg/kg to 8.0 mg/kg, administered via intravenous (IV) solution at 3-week intervals. Dose Finding Part Patritumab Deruxtecan Participants receive 1 of 5 different U3-1402 dosing regimens, administered via IV solution at 2 or 3-week intervals at doses at or lower than those studied in the Dose Escalation Part.
- Primary Outcome Measures
Name Time Method Number of Participants Reporting Treatment-emergent Adverse Events (TEAEs) Baseline up to 28 days post last dose, up to approximately 9 months AEs will be collected systematically from signing of the informed consent form (ICF) through 28 days after last dose
Number of Participants With Best Overall Tumor Response Using Blinded Independent Central Review Based on Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1 From screening until disease progresses, up to approximately 9 months CR was defined as a disappearance of all target and non-target lesions, PR was defined as at least a 30% decrease in the sum of diameters of target and non-target lesions, and stable disease (SD) was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD; at least a 20% increase in the sum of diameters of target and non-target lesions. Objective response rate is the number of patients with confirmed complete response and confirmed partial response.
- Secondary Outcome Measures
Name Time Method Dose Escalation Part: Area Under the Serum Concentration Time Curve (AUC) of Anti-HER3-ac-DXd Cycle 1, Day 1 to Cycle 3, Day 21 (each cycle is 21 days) The serum concentrations for anti-HER3-ac-DXd were quantified using the IC-LC/MS assay.
Dose Finding Part: AUC of Anti-HER3-ac-DXd Cycle 1, Day 1 to Cycle 4, Day 21 (each cycle is 21 days) The serum concentrations for anti-HER3-ac-DXd were quantified using the IC-LC/MS assay.
Dose Expansion Part: AUC of Anti-HER3-ac-DXd Cycle 1, Day 1 to Cycle 3, Day 21 (each cycle is 21 days) The serum concentrations for anti-HER3-ac-DXd were quantified using the IC-LC/MS assay.
Dose Escalation Part: Maximum Plasma Concentration (Cmax) of Anti-HER3-ac-DXd Cycle 1, Day 1 to Cycle 3, Day 21 (each cycle is 21 days) The serum concentrations for anti-HER3-ac-DXd were quantified using the IC-LC/MS assay.
Dose Finding Part: Cmax of Anti-HER3-ac-DXd Cycle 1, Day 1 to Cycle 4, Day 21 (each cycle is 21 days) The serum concentrations for anti-HER3-ac-DXd were quantified using the IC-LC/MS assay.
Dose Expansion Part: Cmax of Anti-HER3-ac-DXd Cycle 1, Day 1 to Cycle 3, Day 21 (each cycle is 21 days) The serum concentrations for anti-HER3-ac-DXd were quantified using the IC-LC/MS assay.
Dose Escalation Part: Time to Maximum Plasma Concentration (Tmax) of Anti-HER3-ac-DXd Cycle 1, Day 1 to Cycle 3, Day 21 (each cycle is 21 days) The serum concentrations for anti-HER3-ac-DXd were quantified using the IC-LC/MS assay.
Dose Finding Part: Tmax of Anti-HER3-ac-DXd Cycle 1, Day 1 to Cycle 4, Day 21 (each cycle is 21 days) The serum concentrations for anti-HER3-ac-DXd were quantified using the IC-LC/MS assay.
Dose Expansion Part: Tmax of Anti-HER3-ac-DXd Cycle 1, Day 1 to Cycle 3, Day 21 (each cycle is 21 days) The serum concentrations for anti-HER3-ac-DXd were quantified using the IC-LC/MS assay.
Dose Escalation Part: Area Under the Concentration-Time Curve of Total Anti-HER3 Antibody Cycle 1, Day 1 to Cycle 3, Day 21 (each cycle is 21 days) The serum concentrations for total anti-HER3 antibody LC/MS were quantified using the IC-LC/MS assay.
Dose Finding Part: Area Under the Concentration-Time Curve in Total Anti-HER3 Antibody Cycle 1, Day 1 to Cycle 4, Day 21 (each cycle is 21 days) The serum concentrations for total anti-HER3 antibody LC/MS were quantified using the IC-LC/MS assay.
Dose Expansion Part: Area Under the Concentration-Time Curve in Total Anti-HER3 Antibody Cycle 1, Day 1 to Cycle 3, Day 21 (each cycle is 21 days) The serum concentrations for total anti-HER3 antibody LC/MS were quantified using the IC-LC/MS assay.
Dose Escalation Part: Cmax of Total Anti-HER3 Antibody Cycle 1, Day 1 to Cycle 3, Day 21 (each cycle is 21 days) The serum concentrations for total anti-HER3 antibody LC/MS were quantified using the IC-LC/MS assay.
Dose Finding Part: Cmax of Anti-HER3 Antibody Cycle 1, Day 1 to Cycle 4, Day 21 (each cycle is 21 days) The serum concentrations for total anti-HER3 antibody LC/MS were quantified using the IC-LC/MS assay.
Dose Expansion Part: Cmax in Anti-HER3 Antibody Cycle 1, Day 1 to Cycle 3, Day 21 (each cycle is 21 days) The serum concentrations for total anti-HER3 antibody LC/MS were quantified using the IC-LC/MS assay.
Dose Escalation Part: Tmax of Total Anti-HER3 Antibody Cycle 1, Day 1 to Cycle 3, Day 21 (each cycle is 21 days) The serum concentrations for total anti-HER3 antibody LC/MS were quantified using the IC-LC/MS assay.
Dose Finding Part: Tmax of Anti-HER3 Antibody Cycle 1, Day 1 to Cycle 4, Day 21 (each cycle is 21 days) The serum concentrations for total anti-HER3 antibody LC/MS were quantified using the IC-LC/MS assay.
Dose Expansion Part: Tmax in Anti-HER3 Antibody Cycle 1, Day 1 to Cycle 3, Day 21 (each cycle is 21 days) The serum concentrations for total anti-HER3 antibody LC/MS were quantified using the IC-LC/MS assay.
Trial Locations
- Locations (26)
Dana Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
Southeastern Regional Medical Center
🇺🇸Newnan, Georgia, United States
Northwestern University
🇺🇸Chicago, Illinois, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Albert Einstein College of Medicine
🇺🇸Bronx, New York, United States
Texas Oncology, P.A.
🇺🇸Dallas, Texas, United States
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
University of Texas MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
UT Southwestern Medical Center
🇺🇸Dallas, Texas, United States
National Cancer Center Hospital East
🇯🇵Chiba, Japan
Mays Cancer Center
🇺🇸San Antonio, Texas, United States
Local Independent Administrative Corporation Hiroshima City Hospital Organization Hiroshima City Hiroshima Citizens Hospital
🇯🇵Hiroshima, Japan
National Hospital Organization Hokkaido Cancer Center
🇯🇵Sapporo-Shi, Hokkaido, Japan
Kumamoto University Hospital
🇯🇵Kumamoto, Japan
Osaka International Cancer Institute
🇯🇵Osaka, Japan
Hakuaikai Social Medical Corporation Sagara Hospital
🇯🇵Kagoshima, Japan
Fukushima Medical University Hospital
🇯🇵Fukushima, Japan
Nagoya City University Hospital
🇯🇵Nagoya, Japan
National Cancer Center Hospital
🇯🇵Tokyo, Japan
Kanagawa Cancer Center
🇯🇵Kanagawa, Japan
Aichi Cancer Center Hospital
🇯🇵Nagoya, Japan
National Hospital Organization Osaka National Hospital
🇯🇵Osaka, Japan
Kindai University Hospital
🇯🇵Osaka, Japan
Saitama Medical University International Medical Center
🇯🇵Saitama, Japan
Saitama Cancer Center
🇯🇵Saitama, Japan
The Cancer Institute Hospital of Japanese Foundation for Cancer Research
🇯🇵Tokyo, Japan