Clinical Trials /

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

NCT02980341

Description:

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.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

    <li>Brief Title: Phase I/II Study of U3-1402 in Subjects With Human Epidermal Growth Factor Receptor 3 (HER3) Positive Metastatic Breast Cancerli><li>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 Cancerli>

Clinical Trial IDs

    <li>ORG STUDY ID: U31402-A-J101li><li>SECONDARY ID: JapicCTI-163401li><li>NCT ID: NCT02980341li>

Conditions

    <li>Metastatic Breast Cancerli>

Interventions

<td>U3-1402td><td>Experimental drugtd><td>Dose Escalation Parttd>
DrugSynonymsArms

Purpose

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.

Trial Arms

<td>Dose Escalation Parttd><td>Experimentaltd><td>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.td><td>
    <li>U3-1402li>
td><td>Dose Finding Parttd><td>Experimentaltd><td>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.td><td>
    <li>U3-1402li>
td><td>Dose Expansion Parttd><td>Experimentaltd><td>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.td><td>
    <li>U3-1402li>
td>
NameTypeDescriptionInterventions

Eligibility 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
      
<td>Maximum Eligible Age:td><td>N/Atd><td>Minimum Eligible Age:td><td>18 Yearstd><td>Eligible Gender:td><td>Alltd><td>Healthy Volunteers:td><td>Notd>

Primary Outcome Measures

<td>Measure:td><td>Number of participants experiencing adverse events (AEs)td><td>Time Frame:td><td>within about 6 monthstd><td>Safety Issue:td><td/><td>Description:td><td>AEs will be collected systematically from signing of the informed consent form (ICF) through 28 days after last dosetd>

Secondary Outcome Measures

<td>Measure:td><td>Change in area under the serum concentration time curve (AUC) of U3-1402td><td>Time Frame:td><td>From first dose at Cycle 1, Day 1 to Cycle 8, Day 1, within 24 weeks for each parttd><td>Safety Issue:td><td/><td>Description:td><td>(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 1td>
<td>Measure:td><td>Change in the maximum plasma concentration (Cmax) of U3-1402td><td>Time Frame:td><td>From first dose at Cycle 1, Day 1 to Cycle 8, Day 1, within 24 weeks for each parttd><td>Safety Issue:td><td/><td>Description:td><td>(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 1td>
<td>Measure:td><td>Change in the time to maximum plasma concentration (Tmax) of U3-1402td><td>Time Frame:td><td>From first dose at Cycle 1, Day 1 to Cycle 8, Day 1, within 24 weeks for each parttd><td>Safety Issue:td><td/><td>Description:td><td>(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 1td>
<td>Measure:td><td>Change in the total anti-HER3 antibody from U3-1402td><td>Time Frame:td><td>From first dose at Cycle 1, Day 1 to Cycle 8, Day 1, within 24 weeks for each parttd><td>Safety Issue:td><td/><td>Description:td><td>(Dose Escalation Part) Samples are obtained for total anti-HER3 antibodyat 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 antibodyat Cycle 1, Days 1, 2, 4, 8, 15; Cycle 2, Day 1; Cycle 3, Days 1, 8, 15; Cycles 4, 6, 8; Day 1td>
<td>Measure:td><td>Change in the MAAA-1181 level from U3-1402td><td>Time Frame:td><td>From first dose at Cycle 1, Day 1 to Cycle 8, Day 1, within 24 weeks for each parttd><td>Safety Issue:td><td/><td>Description:td><td>(Dose Escalation Part) Samples are obtained for measurement of MAAA1181 levelat 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 levelat Cycle 1, Days 1, 2, 4, 8, 15; Cycle 2, Day 1; Cycle 3, Days 1, 8, 15; Cycles 4, 6, 8; Day 1td>

Details

<td>Phase:td><td>Phase 1/Phase 2td><td>Primary Purpose:td><td>Interventionaltd><td>Overall Status:td><td>Recruitingtd><td>Lead Sponsor:td><td>Daiichi Sankyo Co., Ltd.td>

Trial Keywords

    <li>Oncologyli><li>HER3li><li>Antibody drug conjugateli><li>Developmental Phase I/IIli>

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