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About
This study aims to evaluate the efficacy and safety of U3-1402 in participants with advanced breast cancer (ABC). 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 treated 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.
Enrollment
Sex
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Volunteers
Inclusion criteria
Contraceptive methods considered highly effective:
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
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:
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:
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 greater 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 :
e. 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.
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:
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:
Participants with past or resolved hepatitis B virus (HBV) infection are eligible if:
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)
Primary purpose
Allocation
Interventional model
Masking
170 participants in 1 patient group
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Central trial contact
Fernanda Mosele, Dr; Barbara Pistilli, Dr
Data sourced from clinicaltrials.gov
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