Patritumab Deruxtecan (U3-1402) in Unresectable Locally Advanced or Metastatic Breast Cancer

  • STATUS
    Recruiting
  • End date
    Jun 11, 2026
  • participants needed
    100
  • sponsor
    Gustave Roussy, Cancer Campus, Grand Paris
Updated on 22 July 2021

Summary

This study aims to evaluate the efficacy and safety of U3-1402 in participants with advanced breast cancer (ABC) and high expression of human epidermal growth factor Receptor 3 (HER3) defined as 75 percent or more of tumor cell expressing HER3 (seen at 10x objective). Participants have to be hormone-receptor positive (HR+) and have to be resistant to endocrine therapy and cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitors. Participants may have received multiple lines of endocrine therapy with or without targeted therapies and must have received only one line of chemotherapy for ABC.

Moreover, the immune effects, the predictors of resistance and response to treatment, the effect of the chemotherapy on deoxyribonucleic acid (DNA) replication will be assessed and will help identify the subgroups that will mostly benefit from the treatment. The pharmacokinetics of the product and the anti-drug antibody (ADA) will be also evaluated.

A total of 100 participants are planned to be included in the study. Participants will receive, every three weeks, a dose of U3-1402 equivalent to 5.6 mg/kg of body weight until progression or until unacceptable toxicity.

Tumor evaluation will be performed every six weeks by the mean of a computed tomography for the thorax, abdomen and pelvis (TAP CT-scan) or a magnetic resonance imaging (MRI). Brain and/or bone CT scans will be also performed throughout the study for participants with brain and/or bone metastasis.

The safety of the product will be assessed at each cycle, through complete clinical exams, biological tests, electrocardiograms (ECGs), cardiac echographies (ECHOs) and through the collection of ongoing toxicities or adverse events.

Details
Condition Stage IV Breast Cancer, Metastatic Breast Cancer
Treatment U3-1402
Clinical Study IdentifierNCT04965766
SponsorGustave Roussy, Cancer Campus, Grand Paris
Last Modified on22 July 2021

Eligibility

Yes No Not Sure

Inclusion Criteria

Adults with histologically-confirmed HER3-high (75 percent of tumor cells or more express HER3), HER2 negative, unresectable locally advanced or metastatic breast cancer that HR+ is at the time of the first breast cancer diagnosis
Participants with a documented radiologic unresectable or metastatic progression
Participants may have received anthracyclines and taxanes as (neo) adjuvant treatment and must have received one line of chemotherapy for Advanced breast cancer (ABC), but not more than one line. Participants must have a clinically or radiologically documented evidence of tumor progression on or after cyclin dependent kinase 4/6 (CDK 4/ 6) inhibitor combined with endocrine therapy. Previous treatments with PI3K inhibitors, mTOR inhibitors, AKT-inhibitors and poly ADP ribose polymerase (PARP)-inhibitors are allowed
Participants must have metastatic site easily accessible to biopsy (with exception of bone metastasis)
Participants must have at least one radiologically measurable lesion (different from the biopsy site)
Participants must have an ECOG PS equals to 0 or 1
Participants must have a life expectancy of 12 weeks or more
Participants must have adequate bone marrow reserve and organ function, based on local laboratory data within 14 days prior to Cycle 1, Day 1
Females of reproductive/childbearing potential must have a negative serum pregnancy test at screening and must agree to use a highly effective form of contraception or avoid intercourse during the study and for at least 7 months after the last dose of study drug
Contraceptive methods considered highly effective
Intrauterine device (IUD)
Bilateral tubal occlusion
Vasectomized partner
Complete sexual abstinence during and upon completion of the study and for at least 7 months for females after the last dose of study drug
Female participants must not donate, or retrieve for their own use, ova from
the time of screening and for at least 7 months after the final study drug
administration
If male, the participant must be surgically sterile, must withhold heterosexual intercourse, or must be willing to use a highly effective birth control upon enrollment, and for at least 4 months following the last dose of study drug
Male participants must not freeze or donate sperm starting at screening and
throughout the study period, and for at least 4 months after the final study
drug administration
Participant must understand, sign, and date the written ICF prior to any protocol-specific procedures performed. Participant should be able and willing to comply with study visits and procedure as per protocol
Participant must be affiliated to a social security system or beneficiary of the same

Exclusion Criteria

Breast cancer amenable for resection or radiation therapy with curative intent
Any history of interstitial lung disease (ILD), actual ILD, or a suspicion of an ILD
Clinically severe pulmonary compromise (based on investigator's assessment) resulting from intercurrent pulmonary illnesses including, but not limited to
Any underlying pulmonary disorder
Any autoimmune, connective tissue or inflammatory disorder with pulmonary involvement
OR prior pneumonectomy
The use of chronic systemic corticosteroids at a dose superior to 10 mg of prednisone or equivalent or any form of immunosuppressive therapy prior to Cycle 1 Day 1. Participants who require use of bronchodilators, inhaled steroids, or local steroid injections may be included in the study
Evidence of any leptomeningeal disease
Evidence of corneal disease
Any evidence of severe or uncontrolled systemic diseases including active bleeding diatheses, active infection, psychiatric illness/social situations, geographical factors, substance abuse, or other factors which in the investigator's opinion makes it undesirable for the participant to participate in the study or which would jeopardize compliance with the protocol
Evidence of clinically active spinal cord compression or brain metastases defined as untreated and symptomatic, or requiring therapy with corticosteroids or anticonvulsants to control associated symptoms
Inadequate washout period prior to Cycle 1 Day 1, defined as
Whole brain radiation therapy within 14 days before treatment or stereotactic brain radiation therapy, within 7 days before treatment b. Any cytotoxic chemotherapy, investigational agents or other anticancer drug(s) from a previous cancer treatment regimen or clinical study (other than Epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI)), within 14 days before treatment or 5 half-lives, whichever is longer Immune checkpoint inhibitor therapy, within 21 days before treatment d. Endocrine therapy within 21 days of treatment e. Major surgery (excluding placement of vascular access) within 28 days of treatment f. Radiotherapy treatment to more than 30% of the bone marrow or with a wide field of radiation within 28 days or palliative radiation therapy within 14 days of treatment g. Chloroquine or hydroxychloroquine within 14 days before treatment h. Live virus vaccination, within 28 days before treatment
Prior treatment with an anti-HER3 antibody and/or ADC containing an exatecan derivative that is a topoisomerase I inhibitor
Participants with a grade equals or less than 2 unresolved toxicities from previous anticancer therapy (other than alopecia)
A history of severe hypersensitivity reactions to either the drug substances or inactive ingredients of U3-1402, or to other monoclonal antibodies
Any evidence of primary malignancy other than locally advanced or metastatic lung cancer within three years prior to Cycle 1 Day 1, except adequately resected non-melanoma skin cancer, curatively treated in-situ disease, or other solid tumors curatively treated
Uncontrolled or significant cardiovascular disease prior to Cycle 1 Day
Corrected QT interval higher than 470 ms for females and 450 ms for males according to Fridericia's formula (QTcF) and assessed based on triplicate ECGs, approximately 1 minute apart
Left ventricular ejection fraction (LVEF) less than 50% by either ECHO or cardiac MRI
Resting systolic blood pressure higher than 140 mmHg or diastolic blood pressure higher than 90 mmHg
Myocardial infarction within six months f. NYHA Classes 2 to 4 within 28 days before treatment g. Uncontrolled angina pectoris within six months. h. Cardiac arrhythmia requiring antiarrhythmic treatment
Active hepatitis B and/or hepatitis C infection, such as those with serologic evidence of viral infection within 28 days of Cycle 1, Day 1
Hepatitis surface antigen (HBsAg) negative and hepatitis B core antibody (anti-HBc) positive; OR
HBsAg positive and HBV DNA viral load is documented to be equal or less than 2,000 IU/mL in the absence of anti-viral therapy and during the previous 12 weeks prior to the viral load evaluation with normal transaminases (in the absence of liver metastasis); OR
HBsAg positive and HBV DNA viral load is documented to be equal or less than 2,000 IU/mL in the absence of anti-viral therapy and during the previous 12 weeks prior to the viral load evaluation with liver metastasis and abnormal transaminases AST/ALT less than 3 ULN
Participants with a history of Hepatitis C infection will be eligible for
enrollment only if the viral load according to local standards of detection
is documented to be below the level of detection in the absence of anti-viral
therapy during the previous 12 weeks (ie, sustained viral response according
to the local product label but no less than 12 weeks, whichever is longer)
Known human immunodeficiency virus (HIV) or active COVID-19 infection
Participants under guardianship or deprived of his/her liberty by a judicial or administrative decision or incapable of giving his/her consent
Female participants who are pregnant or breastfeeding or intend to become pregnant during the study
Participation in another clinical trial evaluating an experimental drug (except non-interventional research)
Evidence of clinically active spinal cord compression or brain metastases, defined as untreated and symptomatic, or requiring therapy with corticosteroids or anticonvulsants to control associated symptoms. Participants with clinically inactive or treated brain metastases who are asymptomatic (ie, without neurologic signs or symptoms and do not require treatment with corticosteroids or anticonvulsants) may be included in the study. Participants must have a stable neurologic status for at least 2 weeks prior to Cycle 1 Day 1
Inadequate washout period prior to Cycle 1 Day 1, defined as
Whole brain radiation therapy within 14 days before treatment or stereotactic brain radiation therapy, within 7 days before treatment
Any cytotoxic chemotherapy, investigational agents or other anticancer drug(s) from a previous cancer treatment regimen or clinical study (other than epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI)), within 14 days before treatment or 5 half-lives, whichever is longer
Immune checkpoint inhibitor therapy, within 21 days before treatment
Endocrine therapy within 21 days before treatment
Major surgery (excluding placement of vascular access), within 28 days before treatment
Radiotherapy treatment to more than 30% of the bone marrow or with a wide field of radiation, within 28 days before treatment or palliative radiation therapy within 14 days before treatment
Chloroquine or hydroxychloroquine within 14 days before treatment
Live virus vaccination, within 28 days before treatment
Prior treatment with an anti-HER3 antibody and/or ADC containing an exatecan derivative that is a topoisomerase I inhibitor (eg, trastuzumab deruxtecan)
Participants with grade 2 unresolved toxicities from previous anticancer therapy (other than alopecia), as defined by the NCI-CTCAE version 5.0
Participant with a known hypersensitivity to either the drug substances or inactive ingredients in the drug product Participant with a history of severe hypersensitivity reactions to other monoclonal antibodies Participant has any primary malignancy other than locally advanced or metastatic breast cancer within 3 years prior to Cycle 1 Day 1, except adequately resected non-melanoma skin cancer, curatively treated in-situ disease, or other solid tumors curatively treated
Uncontrolled or significant cardiovascular disease prior to Cycle 1 Day 1, including
Corrected QT interval higher than 470 ms for females and 450 ms for males according to Fridericia's formula (QTcF) and assessed based on triplicate ECGs, approximately 1 minute apart
Left ventricular ejection fraction (LVEF) less than 50% by either ECHO or cardiac MRI
Resting systolic blood pressure higher than 140 mmHg or diastolic blood pressure higher than 90 mmHg
Myocardial infarction within six months
NYHA Classes 2 to 4 within 28 days before treatment
Uncontrolled angina pectoris within six months
Cardiac arrhythmia requiring antiarrhythmic treatment
Participants with past or resolved hepatitis B virus (HBV) infection are eligible if
Hepatitis surface antigen (HBsAg) negative and hepatitis B core antibody (anti-HBc) positive; OR
HBsAg positive and HBV DNA viral load is documented to be equal or less than 2,000 IU/mL in the absence of anti-viral therapy and during the previous 12 weeks prior to the viral load evaluation with normal transaminases (in the absence of liver metastasis); OR
HBsAg positive and HBV DNA viral load is documented to be equal or less than 2,000 IU/mL in the absence of anti-viral therapy and during the previous 12 weeks prior to the viral load evaluation with liver metastasis and abnormal transaminases AST/ALT less than 3 ULN
Participants with a history of Hepatitis C infection will be eligible for
enrollment only if the viral load according to local standards of detection
is documented to be below the level of detection in the absence of anti-viral
therapy during the previous 12 weeks (ie, sustained viral response according
to the local product label but no less than 12 weeks, whichever is longer)
Female participant who is pregnant or breastfeeding or intends to become pregnant during the study
Participants with human immunodeficiency virus (HIV) or active coronavirus (COVID-19) infection Participants with any psychological, familial, sociological or geographical condition potentially hindering compliance with the study protocol procedures and follow-up schedule Participants under guardianship or deprived of his liberty by a judicial or administrative decision or incapable of giving its consent
Participation in another clinical trial evaluating an experimental drug (except non-interventional research
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