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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 : March 12, 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, non-randomized, 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 : 80 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase 1/2, Multicenter, Non-randomized, 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
U.S. FDA Resources

Arm Intervention/treatment
Experimental: Dose Escalation Part
The maximum tolerated dose is determined in the Dose Escalation Part by administering U3-1402 from 1.6 mg/kg to 9.7 mg/kg, administered via intravenous (IV) solution at 3-week intervals.
Drug: U3-1402
An investigational drug, not yet approved for marketing.
Other Name: Experimental drug
Experimental: Dose Finding Part
The recommended dose is determined in the Dose Finding Part by administering U3-1402 at different doses based on Dose Escalation Part results, administered via IV solution at 3-week intervals.
Drug: U3-1402
An investigational drug, not yet approved for marketing.
Other Name: Experimental drug
Experimental: Dose Expansion Part
The safety and efficacy of the recommended dose is determined in the Dose Expansion Part by administering U3-1402 at the recommended dose determined in the Dose Finding Part, administered via IV solution at 3-week intervals.
Drug: U3-1402
An investigational drug, not yet approved for marketing.
Other Name: Experimental drug



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 ]
    Efficacy assessment of tumor response to U3-1402 is conducted every 6 weeks in the first 24 weeks and thereafter every 12 weeks until progressive disease


Secondary Outcome Measures :
  1. Change in area under the serum concentration time curve (AUC) of U3-1402 [ Time Frame: From first dose at Cycle 1, Day 1 to Cycle 8, Day 1, within 24 weeks for each part ]

    (Dose Escalation Part) Samples are obtained for AUC at Cycle 1, Days 1, 2, 4, 8, 15; Cycle 2, Days 1, 8, 15; Cycle 3, Days 1, 2, 4, 8, 15; Cycle 4, 6, 8; Day 1

    (Dose Finding Part and Dose Expansion Part) Samples are obtained for AUC at Cycle 1, Days 1, 2, 4, 8, 15; Cycle 2, Day 1; Cycle 3, Days 1, 8, 15; Cycle 4, 6, 8; Day 1


  2. Change in the maximum plasma concentration (Cmax) of U3-1402 [ Time Frame: From first dose at Cycle 1, Day 1 to Cycle 8, Day 1, within 24 weeks for each part ]

    (Dose Escalation Part) Samples are obtained for Cmax at Cycle 1, Days 1, 2, 4, 8, 15; Cycle 2, Days 1, 8, 15; Cycle 3, Days 1, 2, 4, 8, 15; Cycle 4, 6, 8; Day 1

    (Dose Finding Part and Dose Expansion Part) Samples are obtained for Cmax at Cycle 1, Days 1, 2, 4, 8, 15; Cycle 2, Day 1; Cycle 3, Days 1, 8, 15; Cycle 4, 6, 8; Day 1


  3. Change in the time to maximum plasma concentration (Tmax) of U3-1402 [ Time Frame: From first dose at Cycle 1, Day 1 to Cycle 8, Day 1, within 24 weeks for each part ]

    (Dose Escalation Part) Samples are obtained for Tmax at Cycle 1, Days 1, 2, 4, 8, 15; Cycle 2, Day 1, 8, 15; Cycle 3, Days 1, 2, 4, 8, 15; Cycle 4, 6, 8; Day 1

    (Dose Finding Part and Dose Expansion Part) Samples are obtained for Tmax at Cycle 1, Days 1, 2, 4, 8, 15; Cycle 2, Day 1; Cycle 3, Days 1, 8, 15; Cycle 4, 6, 8; Day 1


  4. Change in the total anti-HER3 antibody from U3-1402 [ Time Frame: From first dose at Cycle 1, Day 1 to Cycle 8, Day 1, within 24 weeks for each part ]

    (Dose Escalation Part) Samples are obtained for total anti-HER3 antibody 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

    (Dose Finding Part and Dose Expansion Part) Samples are obtained for total anti-HER3 antibody 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


  5. Change in the MAAA-1181 level from U3-1402 [ Time Frame: From first dose at Cycle 1, Day 1 to Cycle 8, Day 1, within 24 weeks for each part ]

    (Dose Escalation Part) Samples are obtained for measurement of MAAA1181 level 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

    (Dose Finding Part and Dose Expansion Part) Samples are obtained for measurement of MAAA1181 level 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




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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
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 no standard treatment 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:

1. Has received 2-6 prior chemotherapy regimens including taxanes in advanced setting

Additional Inclusion Criteria for Dose Expansion Part Only:

  1. Is able to submit a fresh tumor biopsy sample prior to starting study treatment if not already submitted for HER3 expression
  2. Has documented HER2 negative expression according to American Society of Clinical Oncology - College of American Pathologists (ASCO-CAP) guidelines
  3. 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: March 12, 2018
Last Verified: March 2018

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