Clinical Trial - NCT02980341

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

Recruiting

Sponsor: Daiichi Sankyo Co., Ltd.

Collaborators: Daiichi Sankyo, Inc.

Information provided by (Responsible party): Sponsor

ClinicalTrials.gov Identifier: NCT02980341

Protocol Info

Short Description: Phase I/II Study of U3-1402 in Subjects With Human Epidermal Growth Factor Receptor 3 (HER3) Positive Metastatic Breast Cancer
Long Description: Phase 1/2, Multicenter, Open-Label, Multiple Dose, First-in-Human Study of U3-1402 in Subjects with HER3-Positive Metastatic Breast Cancer
MGH Status: Open
Sponsor: Daiichi Sankyo Pharmaceuticals
Disease Program: Breast

Next Steps


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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.
Condition Title Intervention Phase
Metastatic Breast Cancer U3-1402 Phase 1/Phase 2
Study Type Interventional
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

Primary Outcome Measures

Number of participants experiencing adverse events (AEs) [Time Frame: within about 6 months] [Designated as safety issue: ]

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] [Designated as safety issue: ]


Secondary Outcome Measures

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)] [Designated as safety issue: ]

Dose Finding Part: AUC of U3-1402 [Time Frame: Cycle 1, Day 1 to Cycle 8, Day 1 (148 days)] [Designated as safety issue: ]

Dose Expansion Part: AUC of U3-1402 [Time Frame: Cycle 1, Day 1 to Cycle 8, Day 1 (148 days)] [Designated as safety issue: ]

Dose Escalation Part: Maximum plasma concentration (Cmax) of U3-1402 [Time Frame: within 148 days] [Designated as safety issue: ]

Dose Finding Part: Cmax of U3-1402 [Time Frame: within 148 days] [Designated as safety issue: ]

Dose Expansion Part: Cmax of U3-1402 [Time Frame: within 148 days] [Designated as safety issue: ]

Dose Escalation Part: Time to maximum plasma concentration (Tmax) of U3-1402 [Time Frame: within 148 days] [Designated as safety issue: ]

Dose Finding Part: Tmax of U3-1402 [Time Frame: within 148 days] [Designated as safety issue: ]

Dose Expansion Part: Tmax of U3-1402 [Time Frame: within 148 days] [Designated as safety issue: ]

Dose Escalation Part: Change in Total anti-HER3 antibody from U3-1402 [Time Frame: Baseline, 6 months] [Designated as safety issue: ]

Dose Finding Part: Change in Total anti-HER3 antibody from U3-1402 [Time Frame: Baseline, 6 months] [Designated as safety issue: ]

Dose Expansion Part: Change in Total anti-HER3 antibody from U3-1402 [Time Frame: Baseline, 6 months] [Designated as safety issue: ]

Dose Escalation Part: Change in MAAA-1181 level from U3-1402 [Time Frame: within 148 days] [Designated as safety issue: ]

Dose Finding Part: Change in MAAA-1181 level from U3-1402 [Time Frame: within 148 days] [Designated as safety issue: ]

Dose Expansion Part: Change in MAAA-1181 level from U3-1402 [Time Frame: within 148 days] [Designated as safety issue: ]

Estimated Enrollment: 180
Study Start Date: November 2016
Estimated Study Completion Date: December 2020
Estimated Primary Completion Date: September 2020
Arms Assigned Interventions

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.

Experimental:Dose Expansion Part

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.

Eligibility

Ages Eligible for Study: N/A-N/A

Genders Eligible for Study: All

Accepts Healthly Volunteers: No

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 severe 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).

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT02980341

Locations

  • United States, Georgia
    • Southeastern Regional Medical Center Newnan, Georgia, United States, 30265
  • United States, Illinois
    • Northwestern University Chicago, Illinois, United States, 60611
  • United States, Massachusetts
    • Massachusetts General Hospital Boston, Massachusetts, United States, 02114-2752
    • Beth Israel Deaconess Medical Center Boston, Massachusetts, United States, 02215
    • Dana Farber Cancer Institute Boston, Massachusetts, United States, 02215
  • United States, New York
    • Albert Einstein College of Medicine Bronx, New York, United States, 10467
  • United States, Texas
    • Texas Oncology, P.A. Dallas, Texas, United States, 75231
    • UT Southwestern Medical Center Dallas, Texas, United States, 75390
    • University of Texas MD Anderson Cancer Center Houston, Texas, United States, 77030-4009
    • Mays Cancer Center San Antonio, Texas, United States, 78229
  • Japan, Hokkaido
    • National Hospital Organization Hokkaido Cancer Center Sapporo-Shi, Hokkaido, Japan, 003-0804
  • Japan,
    • National Cancer Center Hospital East Chiba, , Japan, 277-8577
    • Fukushima Medical University Hospital Fukushima, , Japan, 960-1295
    • Sagara Hospital Kagoshima, , Japan, 892-0833
    • Kumamoto University Hospital Kumamoto, , Japan, 860-8556
    • Aichi Cancer Center Hospital Nagoya, , Japan, 464-8681
    • Nagoya City University Hospital Nagoya, , Japan, 467-8602
    • National Hospital Organization Osaka National Hospital Osaka, , Japan, 540-0006
    • Osaka International Cancer Institute Osaka, , Japan, 541-8567
    • Kindai University Hospital Osaka, , Japan, 589-8511
    • Saitama Medical University International Medical Center Saitama, , Japan, 350-1298
    • Saitama Cancer Center Saitama, , Japan, 362 0806
    • National Cancer Center Hospital Tokyo, , Japan, 104-0045
    • The Cancer Institute Hospital of Japanese Foundation for Cancer Research Tokyo, , Japan, 135-8550

Sponsors and Collaborators

Daiichi Sankyo Co., Ltd.

Daiichi Sankyo, Inc.

More Information

No publications provided

Responsible Party: Sponsor
ClinicalTrials.gov Identifier: NCT02980341
Other Study ID Numbers: JapicCTI-163401
Study First Received:
Last Updated:
Health Authority:

Keywords provided by Daiichi Sankyo, Inc.:

Oncology

HER3

Antibody drug conjugate

Developmental Phase I/II

Additional relevant MeSH terms:

Breast Neoplasms

Next Steps


If you are interested in this protocol or in other treatment options at Massachusetts General Hospital, please Request a Consultation.







ClinicalTrials.gov processed this data on August 15, 2019