Informations générales (source: ClinicalTrials.gov)
Phase 2, Open Label Study of Patritumab Deruxtecan (U3-1402), an Anti-HER3-Antibody Drug Conjugate (ADC), in Patients With Advanced Breast Cancer, With Biomarker Analyses to Characterize Response to Therapy
Interventional
Phase 2
Gustave Roussy, Cancer Campus, Grand Paris (Voir sur ClinicalTrials)
mai 2021
avril 2030
09 mai 2026
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.
Etablissements
| Les établissements d'Île-de-France ayant mis à jour leurs données Origine et niveau de fiabilité des données | |||||
|---|---|---|---|---|---|
| CLCC INSTITUT CURIE | 10/04/2025 13:12:12 | Contact (sur clinicalTrials) | |||
| CLCC INSTITUT GUSTAVE ROUSSY | Barbara PISTILLI | 24/07/2026 14:40:05 | Contacter | ||
| Les établissements d'Île-de-France dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données | |||||
| AP-HP - Hôpital Tenon | Xavier BARTHERE, MD | Contact (sur clinicalTrials) | |||
| CLCC INSTITUT CURIE | Delphine LOIRAT, MD | Contact (sur clinicalTrials) | |||
| Les établissements hors Île-de-France dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données | |||||
| Centre Léon Bérard - 69373 - Lyon - France | Thomas BACHELOT, MD | Contact (sur clinicalTrials) | |||
| Institut Claudius Regaud - 31059 - Toulouse - France | Florence DALENC, MD | Contact (sur clinicalTrials) | |||
| Institut de Cancérologie de l'Ouest - 44805 - Saint-Herblain - France | Jean-Sébastien FRENEL, MD | Contact (sur clinicalTrials) | |||
| Les établissements sans correspondance certaine dans le répertoire FINESS dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données | |||||
| Centre Antoine Lacassagne - 06189 - Nice - France | Agnès DUCOULOMBIER, MD | Contact (sur clinicalTrials) | |||
| Centre Georges François Leclerc - 21079 - Dijon - France | Contact (sur clinicalTrials) | ||||
| CHU de Limoges - 87042 - Limoges - France | Elise DELUCHE, MD | Contact (sur clinicalTrials) | |||
| Institut Paoli Calmettes - 13273 - Marseille - France | Cécile VICIER, MD | Contact (sur clinicalTrials) | |||
| Institut Régional du Cancer de Montpellier - 34298 - Montpellier - France | Véronique D'HONDT, MD | Contact (sur clinicalTrials) | |||
Critères
Tous
- 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:
1. Hormonal or nonhormonal intrauterine device (IUD)
2. Progestogen-only subdermal contraceptive implant
3. Bilateral tubal occlusion
4. Vasectomized partner
5. 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:
1. Progestogen-only contraceptive implant
2. Hormonal or nonhormonal IUD
3. Bilateral tubal occlusion (includes tubal ligation)
4. Combined (estrogen- and progestogen-containing) hormonal contraception (oral,
intravaginal, transdermal, injectable)
5. Progestogen-only hormonal contraception (oral, injectable)
6. Progesterone-only hormonal contraception where inhibition of ovulation is not
the primary mode of action
7. 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.
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:
1. Any underlying pulmonary disorder
2. Any autoimmune, connective tissue or inflammatory disorder with pulmonary
involvement
3. 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:
1. Whole brain radiation therapy <14 days or stereotactic brain radiation therapy
<7 days.
2. Immune checkpoint inhibitor therapy <21 days
3. Hormonal therapy <21 days
4. Major surgery (excluding placement of vascular access) <28 days.
5. 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.
6. Chloroquine or hydroxychloroquine ≤ 14 days
7. 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 :
1. 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
2. Left ventricular ejection fraction (LVEF) less than 50% by either ECHO or
cardiac MRI or multigated acquisition scan (MUGA)
3. Resting systolic blood pressure higher than 140 mmHg or diastolic blood
pressure higher than 90 mmHg
4. Myocardial infarction within six months
5. Symptomatic congestive heart failure (NYHA Classes 2 to 4 within 28 days before
treatment)
6. Uncontrolled angina pectoris within six months.
7. Cardiac arrhythmia requiring antiarrhythmic treatment
- Evidence of active or uncontrolled hepatitis B virus infection (HBV)
Participants are eligible:
1. If HBsAg positive with chronic HBV infection (lasting 6 months or longer) and meet
conditions below:
- HBV DNA viral load <2000 IU/mL
- Start or maintain antiviral treatment if clinically indicated as per the
investigator.
2. Have normal transaminase values, or, if liver metastases are present, abnormal
transaminases with a result of AST/ALT <3 × ULN, which are not attributable to HBV
infection - Evidence of active or uncontrolled hepatitis C virus infection (HCV).
Participants are eligible if:
1. History of hepatitis C infection eligible if the HCV viral load is below the level
of detection in the absence of antiviral therapy during the previous 4 weeks
2. Have normal transaminase values, or, if liver metastases are present, abnormal
transaminases with a result of AST/ALT < 3 × ULN, which are not attributable to HCV
infection - Evidence of active or uncontrolled human immunodeficiency virus (HIV
infection. Subjects must be tested for HIV viral load during the Screening Period if
acceptable by local regulations or IRBs/IECs.
Participants are eligible if:
1. CD4+ T-cell count ≥350 cells/mm3 at the time of screening 16
2. Virologic suppression defined as confirmed HIV RNA level below 50 or the LLOQ (below
the limit of detection) at the time of screening and for at least 12 weeks before
screening
3. No AIDS-defining opportunistic infections or conditions within the past 12 months
4. On stable ART regimen, without changes in drugs or dose modification, for at least 4
weeks before trial entry (Day 1) and agree to continue ART throughout the trial.
- Prior or ongoing clinically relevant illness, medical condition, surgical
history, physical finding, or laboratory abnormality that, in the
Investigator's judgment, could affect the safety of the subject; alter the
absorption, distribution, metabolism or excretion of the study drug; or
confound the assessment of study results.
- Evidence of ongoing uncontrolled systemic bacterial, fungal, or viral
infection. Subjects with localized fungal infections of skin or nails are
eligible.
- Female patient who is pregnant or breastfeeding or intends to become pregnant
during the study.
- Patient with any psychological, familial, sociological or geographical
condition potentially hindering compliance with the study protocol procedures
and follow-up schedule.
- Patient 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