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

Recruiting now · Phase 2

Conditions studied: Metastatic Breast Cancer, Advanced Breast Cancer

In brief

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 99 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. A PET scan combined with contrast enhanced CT scan can replace all the above-mentioned imaging if performed at baseline considering that the same imaging technique should be used throughout the study. 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.

Key facts

Study ID: NCT04965766
Run by: Gustave Roussy, Cancer Campus, Grand Paris
People needed: 139
Starts: 2021-05-11
Expected to finish: 2030-04-11
Last updated by the study team: 2025-12-23

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

Adults with histologically-confirmed HER2 negative, unresectable locally advanced or metastatic breast cancer that is hormone receptor positive (HR+) 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 a tumor 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
Female patients of reproductive/childbearing potential must have a negative pregnancy test at screening (serum test within 14 days or urine test within 72 hours of enrollment). A positive urine pregnancy test result must be confirmed by a serum test. Patients must agree to use a highly effective form of contraception or avoid intercourse during and upon completion of the study and for at least 7 months after the last dose of study drug.
The following contraception methods are considered highly effective:
Hormonal or nonhormonal intrauterine device (IUD)
Progestogen-only subdermal contraceptive implant
Bilateral tubal occlusion
Vasectomized partner
Complete sexual abstinence defined as refraining from heterosexual intercourse during and upon completion of the study and for at least 7 months for females after the last dose of study drug.
Periodic abstinence (calendar, symptothermal, post-ovulation methods) is not an acceptable method of contraception. Penile/external condoms for male partners must be used in addition to the female patient's hormonal contraception for the duration treatment intervention and until 7 months following the last dose of trial intervention. Female patients must not donate, or retrieve for their own use, ova from the time of screening and throughout the study treatment period, and for at least 7 months after the final study drug administration.
A male participant capable of producing sperm is eligible to participate if he agrees to the following during the intervention period and for at least the time needed to eliminate each trial intervention. The length of time required to continue contraception after last dose for each trial intervention is 4 months. Avoid donating sperm. Note: Preservation of sperm should be considered prior to enrollment/randomization in this trial. Use a penile/external condom when having penile-vaginal intercourse with a nonparticipant of childbearing potential, PLUS partner use of an additional contraceptive method (see below), as a condom may break or leak:
Progestogen-only contraceptive implant
Hormonal or nonhormonal IUD
Bilateral tubal occlusion (includes tubal ligation)
Combined (estrogen- and progestogen-containing) hormonal contraception (oral, intravaginal, transdermal, injectable)
Progestogen-only hormonal contraception (oral, injectable)
Progesterone-only hormonal contraception where inhibition of ovulation is not the primary mode of action
Cervical cap, diaphragm, or sponge with spermicide Contraceptive use should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
If the contraception requirements in the local label for any of the trial interventions are more stringent than the requirements above, the local label requirements are to be followed. Note: If the participant is azoospermic (vasectomized or secondary to medical cause, documented from the site personnel's review of the participant's medical records, medical examination, or medical history interview), no contraception is required.

You may not qualify if…

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 daily 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
Exposure to prior systemic anticancer therapy (including investigational agents) within 4 weeks or 5 half-lives (whichever is shorter) before enrollment.
Inadequate washout period prior to Cycle 1 Day 1, defined as:
Whole brain radiation therapy <14 days or stereotactic brain radiation therapy <7 days.
Immune checkpoint inhibitor therapy <21 days
Hormonal therapy <21 days
Major surgery (excluding placement of vascular access) <28 days.
Radiotherapy treatment to more than 30% of the bone marrow or with a wide field of radiation <28 days or palliative radiation therapy <14 days.
Chloroquine or hydroxychloroquine ≤ 14 days
Live virus vaccination <28 days.
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 :

Where it is running

Gustave Roussy — Villejuif, France (enrolling)
CHU de Limoges — Limoges, France (enrolling)
Centre Léon Bérard — Lyon, France (enrolling)
Institut Paoli Calmettes — Marseille, France (enrolling)
Institut Régional du Cancer de Montpellier — Montpellier, France (enrolling)
Centre Antoine Lacassagne — Nice, France (enrolling)
Institut Curie — Paris, France (enrolling)
Hôpital Tenon — Paris, France (enrolling)
Institut de Cancérologie de l'Ouest — Saint-Herblain, France (enrolling)
Institut Claudius Regaud — Toulouse, France (enrolling)
Centre Georges François Leclerc — Dijon, France

Full record on ClinicalTrials.gov

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