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Metastatic Breast CancerPhase 1/2NCT02980341

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

A Phase 1/2 study testing Patritumab Deruxtecan in people with Metastatic Breast Cancer, run by Daiichi Sankyo Co., Ltd. at 26 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Metastatic Breast Cancer
What is being tested?
Patritumab Deruxtecan
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
182 participants
Where
26 sitesin 2 countries
Study dates
28 Nov 2016to 7 Sep 2023
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Is 18 Years and older in the United States or 20 Years and older in Japan
  • Has a pathologically documented advanced/unresectable or metastatic breast cancer
  • Documented HER3-positive disease measured by immunohistochemistry (IHC)
  • Has disease that is refractory to or intolerable with standard treatment, or for which standard treatment no longer is available
  • Has an Eastern Cooperative Oncology Group Performance Status 0-1
  • Has Left Ventricular Ejection Fraction ≥ 50%
Show all 15Show fewer
  • 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:
  • 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:
  • Is able to submit a fresh tumor biopsy sample prior to starting study treatment if not already submitted for HER3 expression
  • 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:
  • 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
  • Has progressed after receiving 1 to 2 prior chemotherapy regimens for advanced/unresectable or metastatic breast cancer.

Who cannot join

  • Prior treatment with a HER3 antibody
  • Prior treatment with an antibody-drug conjugate (ADC) which consists of an exatecan derivative that is a topoisomerase I inhibitor (eg, DS-8201)
  • Has a medical history of symptomatic congestive heart failure (New York Heart Association classes II-IV) or serious cardiac arrhythmia requiring treatment
  • Has a medical history of myocardial infarction or unstable angina
  • Has a corrected QT prolongation to > 450 millisecond (ms) in males and > 470 ms in females
  • 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
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  • Has clinically significant corneal disease
  • Additional Exclusion Criteria for Dose Expansion Part:
  • Prior treatment with an govitecan derivative (eg, IMMU-132).

Trial locations and contacts

26 sites in 2 countries.

26 sites in 2 countries

Japan16 sites

  • National Cancer Center Hospital East

    Chiba, 277-8577

  • Fukushima Medical University Hospital

    Fukushima, 960-1295

  • Local Independent Administrative Corporation Hiroshima City Hospital Organization Hiroshima City Hiroshima Citizens Hospital

    Hiroshima, 730-518

  • Hakuaikai Social Medical Corporation Sagara Hospital

    Kagoshima, 892-0833

  • Kanagawa Cancer Center

    Kanagawa, 241-0815

  • Kumamoto University Hospital

    Kumamoto, 860-8556

  • Aichi Cancer Center Hospital

    Nagoya, 464-8681

  • Nagoya City University Hospital

    Nagoya, 467-8602

  • National Hospital Organization Osaka National Hospital

    Osaka, 540-0006

  • Osaka International Cancer Institute

    Osaka, 541-8567

  • Kindai University Hospital

    Osaka, 589-8511

  • Saitama Medical University International Medical Center

    Saitama, 350-1298

  • Saitama Cancer Center

    Saitama, 362 0806

  • National Hospital Organization Hokkaido Cancer Center

    Sapporo, Hokkaido, 003-0804

  • National Cancer Center Hospital

    Tokyo, 104-0045

  • The Cancer Institute Hospital of Japanese Foundation for Cancer Research

    Tokyo, 135-8550

Other trials in Japan

United States10 sites

  • Massachusetts General Hospital

    Boston, Massachusetts, 02114

  • Dana Farber Cancer Institute

    Boston, Massachusetts, 02215

  • Northwestern University

    Chicago, Illinois, 60611

  • Texas Oncology, P.A.

    Dallas, Texas, 75231

  • UT Southwestern Medical Center

    Dallas, Texas, 75390

  • University of Texas MD Anderson Cancer Center

    Houston, Texas, 77030

  • Memorial Sloan Kettering Cancer Center

    New York, New York, 10022

  • Southeastern Regional Medical Center

    Newnan, Georgia, 30265

  • Mays Cancer Center

    San Antonio, Texas, 78229

  • Albert Einstein College of Medicine

    The Bronx, New York, 10467

Other trials in United States

About this study

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

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.

Being tested
Patritumab Deruxtecan
Keywords
Oncology, HER3, Antibody drug conjugate, Developmental Phase I/II
Medical subject headings
Breast Neoplasms, Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Patritumab DeruxtecanDrug

    Also called 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)

Study groups in NCT02980341
Study groupRoleWhat they receive
Dose Escalation PartExperimentalParticipants receive U3-1402 from 1.6 mg/kg to 8.0 mg/kg, administered via intravenous (IV) solution at 3-week intervals.
Receives: Drug: Patritumab Deruxtecan
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.
Receives: Drug: Patritumab Deruxtecan
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.
Receives: Drug: Patritumab Deruxtecan

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Participants Reporting Treatment-emergent Adverse Events (TEAEs)

    AEs will be collected systematically from signing of the informed consent form (ICF) through 28 days after last dose

    Measured: Baseline up to 28 days post last dose, up to approximately 9 months

  2. Number of Participants With Best Overall Tumor Response Using Blinded Independent Central Review Based on Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1

    CR was defined as a disappearance of all target and non-target lesions, PR was defined as at least a 30% decrease in the sum of diameters of target and non-target lesions, and stable disease (SD) was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD; at least a 20% increase in the sum of diameters of target and non-target lesions. Objective response rate is the number of patients with confirmed complete response and confirmed partial response.

    Measured: From screening until disease progresses, up to approximately 9 months

Secondary outcomes (18)

  1. Dose Escalation Part: Area Under the Serum Concentration Time Curve (AUC) of Anti-HER3-ac-DXd

    The serum concentrations for anti-HER3-ac-DXd were quantified using the IC-LC/MS assay.

    Measured: Cycle 1, Day 1 to Cycle 3, Day 21 (each cycle is 21 days)

  2. Dose Finding Part: AUC of Anti-HER3-ac-DXd

    The serum concentrations for anti-HER3-ac-DXd were quantified using the IC-LC/MS assay.

    Measured: Cycle 1, Day 1 to Cycle 4, Day 21 (each cycle is 21 days)

  3. Dose Expansion Part: AUC of Anti-HER3-ac-DXd

    The serum concentrations for anti-HER3-ac-DXd were quantified using the IC-LC/MS assay.

    Measured: Cycle 1, Day 1 to Cycle 3, Day 21 (each cycle is 21 days)

  4. Dose Escalation Part: Maximum Plasma Concentration (Cmax) of Anti-HER3-ac-DXd

    The serum concentrations for anti-HER3-ac-DXd were quantified using the IC-LC/MS assay.

    Measured: Cycle 1, Day 1 to Cycle 3, Day 21 (each cycle is 21 days)

  5. Dose Finding Part: Cmax of Anti-HER3-ac-DXd

    The serum concentrations for anti-HER3-ac-DXd were quantified using the IC-LC/MS assay.

    Measured: Cycle 1, Day 1 to Cycle 4, Day 21 (each cycle is 21 days)

  6. Dose Expansion Part: Cmax of Anti-HER3-ac-DXd

    The serum concentrations for anti-HER3-ac-DXd were quantified using the IC-LC/MS assay.

    Measured: Cycle 1, Day 1 to Cycle 3, Day 21 (each cycle is 21 days)

  7. Dose Escalation Part: Time to Maximum Plasma Concentration (Tmax) of Anti-HER3-ac-DXd

    The serum concentrations for anti-HER3-ac-DXd were quantified using the IC-LC/MS assay.

    Measured: Cycle 1, Day 1 to Cycle 3, Day 21 (each cycle is 21 days)

  8. Dose Finding Part: Tmax of Anti-HER3-ac-DXd

    The serum concentrations for anti-HER3-ac-DXd were quantified using the IC-LC/MS assay.

    Measured: Cycle 1, Day 1 to Cycle 4, Day 21 (each cycle is 21 days)

  9. Dose Expansion Part: Tmax of Anti-HER3-ac-DXd

    The serum concentrations for anti-HER3-ac-DXd were quantified using the IC-LC/MS assay.

    Measured: Cycle 1, Day 1 to Cycle 3, Day 21 (each cycle is 21 days)

  10. Dose Escalation Part: Area Under the Concentration-Time Curve of Total Anti-HER3 Antibody

    The serum concentrations for total anti-HER3 antibody LC/MS were quantified using the IC-LC/MS assay.

    Measured: Cycle 1, Day 1 to Cycle 3, Day 21 (each cycle is 21 days)

  11. Dose Finding Part: Area Under the Concentration-Time Curve in Total Anti-HER3 Antibody

    The serum concentrations for total anti-HER3 antibody LC/MS were quantified using the IC-LC/MS assay.

    Measured: Cycle 1, Day 1 to Cycle 4, Day 21 (each cycle is 21 days)

  12. Dose Expansion Part: Area Under the Concentration-Time Curve in Total Anti-HER3 Antibody

    The serum concentrations for total anti-HER3 antibody LC/MS were quantified using the IC-LC/MS assay.

    Measured: Cycle 1, Day 1 to Cycle 3, Day 21 (each cycle is 21 days)

  13. Dose Escalation Part: Cmax of Total Anti-HER3 Antibody

    The serum concentrations for total anti-HER3 antibody LC/MS were quantified using the IC-LC/MS assay.

    Measured: Cycle 1, Day 1 to Cycle 3, Day 21 (each cycle is 21 days)

  14. Dose Finding Part: Cmax of Anti-HER3 Antibody

    The serum concentrations for total anti-HER3 antibody LC/MS were quantified using the IC-LC/MS assay.

    Measured: Cycle 1, Day 1 to Cycle 4, Day 21 (each cycle is 21 days)

  15. Dose Expansion Part: Cmax in Anti-HER3 Antibody

    The serum concentrations for total anti-HER3 antibody LC/MS were quantified using the IC-LC/MS assay.

    Measured: Cycle 1, Day 1 to Cycle 3, Day 21 (each cycle is 21 days)

  16. Dose Escalation Part: Tmax of Total Anti-HER3 Antibody

    The serum concentrations for total anti-HER3 antibody LC/MS were quantified using the IC-LC/MS assay.

    Measured: Cycle 1, Day 1 to Cycle 3, Day 21 (each cycle is 21 days)

  17. Dose Finding Part: Tmax of Anti-HER3 Antibody

    The serum concentrations for total anti-HER3 antibody LC/MS were quantified using the IC-LC/MS assay.

    Measured: Cycle 1, Day 1 to Cycle 4, Day 21 (each cycle is 21 days)

  18. Dose Expansion Part: Tmax in Anti-HER3 Antibody

    The serum concentrations for total anti-HER3 antibody LC/MS were quantified using the IC-LC/MS assay.

    Measured: Cycle 1, Day 1 to Cycle 3, Day 21 (each cycle is 21 days)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted2 Dec 2016 (estimated)
  2. Study start28 Nov 2016
  3. Primary completion16 Aug 2021
  4. Study completion7 Sep 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
182 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02980341
Sponsor's protocol ID
U31402-A-J101
Other IDs
JapicCTI-163401
Status last verified
Oct 2024
First submitted
28 Nov 2016
Last updated
30 Oct 2024
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: De-identified individual participant data (IPD) and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. 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://vivli.org/ourmember/daiichi-sankyo/ .

Publications

  • Krop IE, Masuda N, Mukohara T, Takahashi S, Nakayama T, Inoue K, Iwata H, Yamamoto Y, Alvarez RH, Toyama T, Takahashi M, Osaki A, Saji S, Sagara Y, O'Shaughnessy J, Ohwada S, Koyama K, Inoue T, Li L, Patel P, Mostillo J, Tanaka Y, Sternberg DW, Sellami D, Yonemori K. Patritumab Deruxtecan (HER3-DXd), a Human Epidermal Growth Factor Receptor 3-Directed Antibody-Drug Conjugate, in Patients With Previously Treated Human Epidermal Growth Factor Receptor 3-Expressing Metastatic Breast Cancer: A Multicenter, Phase I/II Trial. J Clin Oncol. 2023 Dec 20;41(36):5550-5560. doi: 10.1200/JCO.23.00882. Epub 2023 Oct 6.

    PubMed 37801674

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Patritumab Deruxtecan in people with Metastatic Breast Cancer, run by Daiichi Sankyo Co., Ltd. at 26 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 15 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 30 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 26 sites in Japan, United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 13 Aug 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants Reporting Treatment-emergent Adverse Events (TEAEs) (time frame: Baseline up to 28 days post last dose, up to approximately 9 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02980341, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Oct 2024.

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