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

NCT04965766 | Recruiting Phase 2

• 3 other identifiers: 2020-005722-282020/31882023-505923-30-00
• Study Type: interventional
• Target: 139
• Locations: 1 country
• Sites: 11

Brief Summary

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.

Conditions

Metastatic Breast Cancer; Advanced Breast Cancer

Keywords

Metastatic breast cancer; Advanced breast cancer; Unresectable breast cancer; HER2- Breast Cancer; Hormone-receptor positive breast cancer; HR+ breast cancer; Antibody drug conjugate; ADC; Patritumab deruxtecan; U3-1402; Refractory metastatic breast cancer; HER2 Negative; MBC; ABC; Metastatic BC; Advanced BC; Unresectable BC; Refractory advanced breast cancer; Refractory ABC; Refractory MBC; HER3-DXd; estrogen receptor positive; progesterone receptor positive; ER+; PR+; ER+/PR+

Outcome Measures

Primary Outcomes (1)

• Evaluation of objective response rate (ORR) based on investigator assessment

  Defined as the proportion of participants who achieved a confirmed complete response (CR) or partial response (PR) assessed by investigators

  During treatment period, an average of 8 months

Secondary Outcomes (14)

• Evaluation of duration of response (DOR, investigator-assessed and as per retrospective central review)

  From cycle 3 (Week 6) up to 3 years after the EoT, an average of 42 months

• Evaluation of progression free Survival (PFS), investigator-assessed and as per retrospective central review

  From cycle 3 (Week 6) up to 3 years after the EoT, an average of 42 months

• Evaluation of clinical benefit ratio (CBR), investigator-assessed and as per retrospective central review

  From cycle 3 (Week 6) up to 3 years after the EoT, an average of 42 months

• Percentage of patients experiencing adverse events

  During treatment (at each cycle), at EoT and up to 47 days after EoT, an average of 9 months

• Frequency of treatment emergent adverse events (TEAEs) leading to change in treatment dose

  During treatment, an average of 8 months

Study Arms (1)

U3-1402

EXPERIMENTAL

All participants enrolled in the study will receive U3-1402 at a dose of 5.6 mg/kg every 3 weeks until progression or until unacceptable toxicity

Drug: U3-1402

Interventions

U3-1402 DRUG

U3-1402 is uniquely designed to target HER3-a receptor that contributes to treatment resistance and poor prognosis in hormone receptor-positive, HER2-negative (HR+/HER2-) breast cancer patients. This drug is distinct from other interventions due to its composition as an antibody-drug conjugate (ADC): a monoclonal antibody against HER3 conjugated to a topoisomerase I inhibitor, which specifically targets HER3-overexpressing tumor cells. The drug is delivered via a cleavable linker that allows for controlled release of the chemotherapeutic agent within the cancer cells, minimizing systemic side effects.

Also known as: HER3-DXd

U3-1402

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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.

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

Sponsors & Collaborators

• Daiichi Sankyo: collaborator
• Gustave Roussy, Cancer Campus, Grand Paris: lead

Study Sites (11)

Centre Georges François Leclerc

Dijon, 21079, France

ACTIVE NOT RECRUITING

CHU de Limoges

Limoges, 87042, France

RECRUITING

Centre Léon Bérard

Lyon, 69373, France

RECRUITING

Institut Paoli Calmettes

Marseille, 13273, France

RECRUITING

Institut Régional du Cancer de Montpellier

Montpellier, 34298, France

RECRUITING

Centre Antoine Lacassagne

Nice, 06189, France

RECRUITING

Institut Curie

Paris, 75005, France

RECRUITING

Hôpital Tenon

Paris, 75020, France

RECRUITING

Institut de Cancérologie de l'Ouest

Saint-Herblain, 44805, France

RECRUITING

Institut Claudius Regaud

Toulouse, 31059, France

RECRUITING

Gustave Roussy

Villejuif, 94805, France

RECRUITING

Related Publications (1)

• Pistilli B, Mosele F, Corcos N, Pierotti L, Pradat Y, Le Bescond L, Lacroix-Triki M, Nachabeh G, Alfaro A, Catelain C, Job B, Mami-Chouaib F, Badel S, Farace F, Oulhen M, Kannouche P, Tran DTN, Droin N, Vicier C, Frenel JS, D'Hondt V, Dalenc F, Bachelot T, Ducoulombier A, Benderra MA, Loirat D, Mayeur D, Deluche E, Deneuve J, Cheikh-Hussin R, Guyader P, Signolle N, Godefroy K, Talbot H, Vakalopoulou M, Christodoulidis S, Bernard E, Koudou Y, Sporchia A, Suto F, Li L, Sternberg DW, Michiels S, Andre F, Sellami D, Montagnac G. Patritumab deruxtecan in HR+HER2- advanced breast cancer: a phase 2 trial. Nat Med. 2025 Oct;31(10):3492-3503. doi: 10.1038/s41591-025-03885-3. Epub 2025 Sep 4.

  PMID: 40908353 DERIVED

MeSH Terms

Conditions

Breast Neoplasms

Interventions

patritumab deruxtecan

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Barbara PISTILLI, Dr

  Gustave Roussy, Cancer Campus, Grand Paris

  STUDY DIRECTOR

Central Study Contacts

Barbara PISTILLI, MD

CONTACT

+33 (0)1 42 11 42 11; barbara.pistilli@gustaveroussy.fr

Souad COSSÉ

CONTACT

+33 (0)1 42 11 42 11; souad.cosse@gustaveroussy.fr

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: One group of 139 participants treated with U3-1402

Study Record Dates

• First Submitted: June 3, 2021
• First Posted: July 16, 2021
• Study Start: May 11, 2021
• Primary Completion (Estimated): April 11, 2027
• Study Completion (Estimated): April 11, 2030
• Last Updated: December 23, 2025

Record last verified: 2025-12

Locations

FR (11)