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:

Active, not recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: U31402-A-J101
  • SECONDARY ID: JapicCTI-163401
  • NCT ID: NCT02980341

Conditions

  • Metastatic Breast Cancer

Interventions

DrugSynonymsArms
U3-1402Dose Escalation Part

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Dose Escalation PartExperimentalParticipants receive U3-1402 from 1.6 mg/kg to 9.6 mg/kg, administered via intravenous (IV) solution at 3-week intervals.
  • U3-1402
Dose Finding PartExperimentalParticipants 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.
  • U3-1402
Dose Expansion PartExperimentalParticipants 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.
  • U3-1402

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
             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. (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:

          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 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:

         11. 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

         12. Has progressed after receiving 1 to 2 prior chemotherapy regimens for
             advanced/unresectable or metastatic breast cancer.

        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 radiation pneumonitis) or who are
             suspected to have these diseases by imaging at screening period

          7. Has clinically significant corneal disease

             Additional Exclusion Criteria for Dose Expansion Part:

          8. Prior treatment with an govitecan derivative (eg, IMMU-132).
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

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

Secondary Outcome Measures

Measure: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)
Safety Issue:
Description: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
Measure:Dose Finding Part: AUC of U3-1402
Time Frame:Cycle 1, Day 1 to Cycle 8, Day 1 (148 days)
Safety Issue:
Description: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
Measure:Dose Expansion Part: AUC of U3-1402
Time Frame:Cycle 1, Day 1 to Cycle 8, Day 1 (148 days)
Safety Issue:
Description: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
Measure:Dose Escalation Part: Maximum plasma concentration (Cmax) of U3-1402
Time Frame:within 148 days
Safety Issue:
Description:
Measure:Dose Finding Part: Cmax of U3-1402
Time Frame:within 148 days
Safety Issue:
Description:
Measure:Dose Expansion Part: Cmax of U3-1402
Time Frame:within 148 days
Safety Issue:
Description:
Measure:Dose Escalation Part: Time to maximum plasma concentration (Tmax) of U3-1402
Time Frame:within 148 days
Safety Issue:
Description:
Measure:Dose Finding Part: Tmax of U3-1402
Time Frame:within 148 days
Safety Issue:
Description:
Measure:Dose Expansion Part: Tmax of U3-1402
Time Frame:within 148 days
Safety Issue:
Description:
Measure:Dose Escalation Part: Change in Total anti-HER3 antibody from U3-1402
Time Frame:Baseline, 6 months
Safety Issue:
Description:
Measure:Dose Finding Part: Change in Total anti-HER3 antibody from U3-1402
Time Frame:Baseline, 6 months
Safety Issue:
Description:
Measure:Dose Expansion Part: Change in Total anti-HER3 antibody from U3-1402
Time Frame:Baseline, 6 months
Safety Issue:
Description:
Measure:Dose Escalation Part: Change in MAAA-1181 level from U3-1402
Time Frame:within 148 days
Safety Issue:
Description:
Measure:Dose Finding Part: Change in MAAA-1181 level from U3-1402
Time Frame:within 148 days
Safety Issue:
Description:
Measure:Dose Expansion Part: Change in MAAA-1181 level from U3-1402
Time Frame:within 148 days
Safety Issue:
Description:

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Daiichi Sankyo Co., Ltd.

Trial Keywords

  • Oncology
  • HER3
  • Antibody drug conjugate
  • Developmental Phase I/II

Last Updated

January 10, 2020