Patritumab Deruxtecan (U3-1402) in Unresectable Locally Advanced or Metastatic Breast Cancer
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorGustave Roussy, Cancer Campus, Grand Paris
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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)
Disqualifiers
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
Any underlying pulmonary disorder
Any autoimmune, connective tissue or inflammatory disorder with pulmonary involvement
Trial design
Design model
Single group
Treatments tested in this trial
U3-1402
DrugU3-1402 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.
Treatment groups
139 Participants
are divided into 1 treatment groupGroup A: U3-1402Experimental treatment 1 intervention
Trial outcomes
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
Time frame
During treatment period, an average of 8 monthsSecondary outcomes
1
Evaluation of duration of response (DOR, investigator-assessed and as per retrospective central review)
Applicable to participants with either complete response (CR) or partial response (PR) and is defined as the time from the first documented CR or PR until the date of disease progression, or until the date of death. It will be evaluated in the overall population and in subgroups of patients according to investigator assessment and as per retrospective central review
Time frame
From cycle 3 (Week 6) up to 3 years after the EoT, an average of 42 months2
Evaluation of progression free Survival (PFS), investigator-assessed and as per retrospective central review
Defined as the time date of the first dose until progression or death from any cause, whichever occurs first. It will be evaluated in the overall population according to investigator assessment and as per retrospective central review
Time frame
From cycle 3 (Week 6) up to 3 years after the EoT, an average of 42 months3
Evaluation of clinical benefit ratio (CBR), investigator-assessed and as per retrospective central review
Defined as the presence of at least a PR or CR, or a stable disease (SD) for more than six months under treatment. It will be evaluated in the overall population according to investigator assessment and as per retrospective central review
Time frame
From cycle 3 (Week 6) up to 3 years after the EoT, an average of 42 months4
Percentage of patients experiencing adverse events
Time frame
During treatment (at each cycle), at EoT and up to 47 days after EoT, an average of 9 monthsSponsors and contacts
Click on the lead sponsor to view all of their trials.
Gustave Roussy, Cancer Campus, Grand Paris
Lead sponsor
Daiichi Sankyo
Collaborator
Source ClinicalTrials.gov