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Phase I/II Study of U3-1402 in Subjects With Human Epidermal Growth Factor Receptor 3 (HER3) Positive Metastatic Breast Cancer

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ClinicalTrials.gov Identifier: NCT02980341
Recruitment Status : Recruiting
First Posted : December 2, 2016
Last Update Posted : September 6, 2018
Sponsor:
Collaborator:
Daiichi Sankyo, Inc.
Information provided by (Responsible Party):
Daiichi Sankyo, Inc. ( 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), or unacceptable toxicity may continue the study treatment until the end of the trial.


Condition or disease Intervention/treatment Phase
Metastatic Breast Cancer Drug: U3-1402 Phase 1 Phase 2

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 140 participants
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase 1/2, Multicenter, Open-label, Multiple-Dose First-in-human Study of U3-1402, in Subjects With HER3 Positive Metastatic Breast Cancer
Study Start Date : November 2016
Estimated Primary Completion Date : September 2020
Estimated Study Completion Date : December 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arm Intervention/treatment
Experimental: Dose Escalation Part
Participants receive U3-1402 from 1.6 mg/kg to 9.6 mg/kg, administered via intravenous (IV) solution at 3-week intervals.
Drug: U3-1402
U3-1402 consists of an antibody component (patritumab, U3-1287) covalently conjugated to a drug-linker (MAAA-1162a) containing a drug component (MAAA-1181a)

Experimental: Dose Finding Part
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.
Drug: U3-1402
U3-1402 consists of an antibody component (patritumab, U3-1287) covalently conjugated to a drug-linker (MAAA-1162a) containing a drug component (MAAA-1181a)

Experimental: Dose Expansion Part
Participants with HER3 high 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 status receive 6.4 mg/kg of U3-1402 administered via intravenous (IV) solution at 3-week intervals.
Drug: U3-1402
U3-1402 consists of an antibody component (patritumab, U3-1287) covalently conjugated to a drug-linker (MAAA-1162a) containing a drug component (MAAA-1181a)




Primary Outcome Measures :
  1. Number of participants experiencing adverse events (AEs) [ Time Frame: within about 6 months ]
    AEs will be collected systematically from signing of the informed consent form (ICF) through 28 days after last dose

  2. Number of participants with tumor response throughout the study using Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1 [ Time Frame: From screening until disease progresses, within about 6 months ]

Secondary Outcome Measures :
  1. Dose Escalation Part: Area under the serum concentration time curve (AUC) of U3-1402 [ Time Frame: Cycle 1, Day 1 to Cycle 8, Day 1 (148 days) ]
    Samples are obtained for all secondary outcome measures in the Dose Escalation Part at Cycle 1: Days 1, 2, 4, 8, 15; Cycle 2: Days 1, 8, 15; Cycle 3: Days 1, 2, 4, 8, 15; Cycles 4, 6, 8: Day 1

  2. Dose Finding Part: AUC of U3-1402 [ Time Frame: Cycle 1, Day 1 to Cycle 8, Day 1 (148 days) ]

    Samples are obtained for all secondary outcome measures in the Dose Finding Part for the following categories:

    • Cohorts 1 and 2: at Cycle 1: Days 1, 2, 4, 8, 15; Cycle 2: Day 1; Cycle 3: Days 1, 8, 15; Cycles 4, 5, 6, 8: Day 1
    • Cohort 3: at Cycles 1, 2, 3: Days 1, 8, 15; Cycles 4, 5, 6, 8: Day 1
    • Cohorts 4 and 5: at Cycle 1: Days 1, 4, 8; Cycle 2: Day 1; Cycle 3: Days 1, 4, 8; Cycle 4: Days 1, 8, 15; Cycles 5, 6, 8: Day 1

  3. Dose Expansion Part: AUC of U3-1402 [ Time Frame: Cycle 1, Day 1 to Cycle 8, Day 1 (148 days) ]
    Samples are obtained for all secondary outcome measures in the Dose Expansion Part at Cycle 1, Days 1, 2, 4, 8, 15; Cycle 2, Day 1; Cycle 3, Days 1, 8, 15; Cycles 4, 6, 8; Day 1

  4. Dose Escalation Part: Maximum plasma concentration (Cmax) of U3-1402 [ Time Frame: within 148 days ]
  5. Dose Finding Part: Cmax of U3-1402 [ Time Frame: within 148 days ]
  6. Dose Expansion Part: Cmax of U3-1402 [ Time Frame: within 148 days ]
  7. Dose Escalation Part: Time to maximum plasma concentration (Tmax) of U3-1402 [ Time Frame: within 148 days ]
  8. Dose Finding Part: Tmax of U3-1402 [ Time Frame: within 148 days ]
  9. Dose Expansion Part: Tmax of U3-1402 [ Time Frame: within 148 days ]
  10. Dose Escalation Part: Change in Total anti-HER3 antibody from U3-1402 [ Time Frame: Baseline, 6 months ]
  11. Dose Finding Part: Change in Total anti-HER3 antibody from U3-1402 [ Time Frame: Baseline, 6 months ]
  12. Dose Expansion Part: Change in Total anti-HER3 antibody from U3-1402 [ Time Frame: Baseline, 6 months ]
  13. Dose Escalation Part: Change in MAAA-1181 level from U3-1402 [ Time Frame: within 148 days ]
  14. Dose Finding Part: Change in MAAA-1181 level from U3-1402 [ Time Frame: within 148 days ]
  15. Dose Expansion Part: Change in MAAA-1181 level from U3-1402 [ Time Frame: within 148 days ]


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Is 18 Years and older in the United States or 20 Years and older in Japan
  2. Has a pathologically documented advanced/unresectable or metastatic breast cancer
  3. Documented HER3-positive disease measured by immunohistochemistry (IHC)
  4. Has disease that is refractory to or intolerable with standard treatment, or for which standard treatment no longer is available
  5. Has an Eastern Cooperative Oncology Group Performance Status 0-1
  6. Has Left Ventricular Ejection Fraction ≥ 50%
  7. 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:

  8. 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.

    Additional Inclusion Criteria for Dose Expansion Part Only:

  9. Is able to submit a fresh tumor biopsy sample prior to starting study treatment if not already submitted for HER3 expression
  10. Has documented HER2 negative expression according to American Society of Clinical Oncology - College of American Pathologists (ASCO-CAP) guidelines
  11. Has documented hormone (estrogen and/or progesterone) receptor (HR)-positive disease

Exclusion Criteria:

  1. Prior treatment with a HER3 antibody
  2. Prior treatment with an antibody-drug conjugate (ADC) which consists of an exatecan derivative that is a topoisomerase I inhibitor (eg, DS-8201)
  3. Has a medical history of symptomatic congestive heart failure (New York Heart Association classes II-IV) or serious cardiac arrhythmia requiring treatment
  4. Has a medical history of myocardial infarction or unstable angina
  5. Has a corrected QT prolongation to > 450 millisecond (ms) in males and > 470 ms in females
  6. Has a medical history of clinically significant lung diseases (eg, interstitial pneumonia, pneumonitis, pulmonary fibrosis, and severe radiation pneumonitis) or who are suspected to have these diseases by imaging at screening period
  7. Has clinically significant corneal disease

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02980341


Contacts
Contact: Daiichi Sankyo Contact for Clinical Trial Information +81-3-6225-1111(M-F 9-5 JST) dsclinicaltrial@daiichisankyo.co.jp

Locations
Japan
National Hospital Organization Hokkaido Cancer Center Recruiting
Sapporo-Shi, Hokkaido, Japan, 003-0804
National Cancer Center Hospital East Recruiting
Chiba, Japan, 277-8577
Fukushima Medical University Hospital Recruiting
Fukushima, Japan, 960-1295
Kumamoto University Hospital Recruiting
Kumamoto, Japan, 860-8556
Aichi Cancer Center Hospital Recruiting
Nagoya, Japan, 464-8681
Nagoya City University Hospital Recruiting
Nagoya, Japan, 467-8602
National Hospital Organization Osaka National Hospital Recruiting
Osaka, Japan, 540-0006
Osaka International Cancer Institute Recruiting
Osaka, Japan, 541-8567
Saitama Medical University International Medical Center Recruiting
Saitama, Japan, 350-1298
Saitama Cancer Center Recruiting
Saitama, Japan, 362 0806
National Cancer Center Hospital Recruiting
Tokyo, Japan, 104-0045
The Cancer Institute Hospital of Japanese Foundation for Cancer Research Recruiting
Tokyo, Japan, 135-8550
Sponsors and Collaborators
Daiichi Sankyo Co., Ltd.
Daiichi Sankyo, Inc.
Investigators
Study Director: Global Clinical Leader Daiichi Sankyo, Inc.

Responsible Party: Daiichi Sankyo Co., Ltd.
ClinicalTrials.gov Identifier: NCT02980341     History of Changes
Other Study ID Numbers: U31402-A-J101
JapicCTI-163401 ( Registry Identifier: JapicCTI )
First Posted: December 2, 2016    Key Record Dates
Last Update Posted: September 6, 2018
Last Verified: September 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: De-identified individual participant data (IPD) and applicable supporting clinical trial documents may be available upon request at https://www.clinicalstudydatarequest.com//. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://www.clinicalstudydatarequest.com/Study-Sponsors/Study-Sponsors-DS.aspx
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Clinical Study Report (CSR)
Analytic Code
Time Frame: Studies for which the medicine and indication have received European Union (EU) and United States (US), and/or Japan (JP) marketing approval on or after 01 January 2014 or by the US or EU or JP Health Authorities when regulatory submissions in all regions are not planned and after the primary study results have been accepted for publication.
Access Criteria: Formal request from qualified scientific and medical researchers on IPD and clinical study documents from clinical trials supporting products submitted and licensed in the United States, the European Union and/or Japan from 01 January 2014 and beyond for the purpose of conducting legitimate research. This must be consistent with the principle of safeguarding study participants' privacy and consistent with provision of informed consent.
URL: https://www.clinicalstudydatarequest.com/Study-Sponsors/Study-Sponsors-DS.aspx

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Daiichi Sankyo, Inc. ( Daiichi Sankyo Co., Ltd. ):
Oncology
HER3
Antibody drug conjugate
Developmental Phase I/II

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases