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Tests treatment safety and results for Breast Cancer Metastatic
Official title Dose-Expansion Modular Study To Explore the Safety, Tolerability, and Anti-tumor Activity of HER3- DXd Monotherapy and Combinations in Patients With Inoperable Advanced Breast Cancer (ABC) After Progression on T-DXd
ClinicalTrials.gov ID: NCT06298084
What this study is testing
What is Patritumab deruxtecan?
Patritumab deruxtecan is an investigational medicine, being studied as a potential treatment for breast cancer metastatic.
Also referred to as U3-1402, HER3-DXd.
Plain-language explanation of the investigational treatment - it is being studied and is not an approved or proven therapy. The study team can confirm the details.
- What it's testing
- ICARUS-BREAST02 is an open-label, multicenter, phase 1b/2, platform study that aims to evaluate the safety, tolerability, and efficacy of HER3-DXd monotherapy and in combination with other anti-cancer agents in patients with ABC. The first 2 modules will evaluate: i.
- Phase 2: a mid-size study of how well it works
A plain-language read of the study's public ClinicalTrials.gov listing. The study team confirms the details.
Who can take part
Ages 18 and older
You may be able to join if
- Patients must have received prior treatment with T-DXd and presented disease progression while on T-DXd treatment or within 2 months from T-DXd...
- Patients with HER2-positive tumors must have received prior treatment with trastuzumab and taxanes. They may have received prior treatment with T-DM1...
- Patients with HER2-low tumors must have been treated with taxanes. Patients with HR-positive tumors must have received ET and CDK4/6 inhibitors...
- Patients with germline pathogenic BRCA1/2 mutations and HER2-positive or HER2-low breast cancer are eligible to the study but must have received a...
- Female or male patient aged ≥18 years on the day of the ICF signature
You likely can't join if
- The following exclusion criteria are applicable for all modules. Patients will be excluded if they present one of them:
- Patient with a breast cancer amenable for resection or radiation therapy with curative intent
- Patient with any history of ILD (including pulmonary fibrosis or radiation pneumonitis), has current ILD, or is suspected to have ILD as assessed by...
- Patient with clinically severe pulmonary compromise (based on investigator's assessment) resulting from intercurrent pulmonary illnesses including...
- Any underlying pulmonary disorder (eg, pulmonary embolism, severe asthma, severe chronic obstructive pulmonary disease (COPD), restrictive lung...
- Any autoimmune, connective tissue or inflammatory disorder with pulmonary involvement (eg, rheumatoid arthritis, Sjögren's syndrome, sarcoidosis) OR
See the full eligibility criteria
Who can join
- Patients must have received prior treatment with T-DXd and presented disease progression while on T-DXd treatment or within 2 months from T-DXd interruption/discontinuation for any reason, without requiring to be the...
- Patients with HER2-positive tumors must have received prior treatment with trastuzumab and taxanes. They may have received prior treatment with T-DM1 and pertuzumab.
- Patients with HER2-low tumors must have been treated with taxanes. Patients with HR-positive tumors must have received ET and CDK4/6 inhibitors (patients may have received prior treatment with sacituzumab govitecan) If...
- Patients with germline pathogenic BRCA1/2 mutations and HER2-positive or HER2-low breast cancer are eligible to the study but must have received a prior treatment with PARP inhibitor (olaparib or talazoparib)
- Female or male patient aged ≥18 years on the day of the ICF signature
- Patient who has histologically confirmed diagnosis of breast cancer with unresectable loco regional or metastatic disease
- Patient must have an ECOG PS ≤1 at the time of screening
- Patients must have HER2-pos (IHC 3+ or IHC2+/ISH positive) or HER-2 low (IHC2+/ISH negative or IHC 1+) tumors with any HR status, any time before T-DXd exposure
- Patient must have at least one radiologically measurable lesion (different from the biopsy site) according to response evaluation criteria in solid tumors (RECIST) V1.1 criteria. At least one predominantly lytic or...
- Patient must have a tumor site easily accessible to biopsy, avoiding bone biopsy when possible. Patients must have accepted to perform pre-treatment, on-treatment, and end-of-treatment biopsies
- Patient must have adequate bone marrow reserve and organ function, based on local laboratory data within 14 days prior to Cycle 1, Day 1, defined per the protocol
- Female patients of reproductive/childbearing potential must have a negative pregnancy test at screening (serum test within 24 hours before C1D1 or urine test within 72 hours of C1D1) and must and must agree to use a...
- Intrauterine device (IUD)
- Bilateral tubal occlusion
- Vasectomized partner
- Complete sexual abstinence defined as refraining from heterosexual intercourse during and till the end of treatment and for at least 8 months for females after the last dose of study drug. Periodic abstinence not an...
- 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 8 months after the final study drug administration
- Male patients must be surgically sterile or must withhold heterosexual intercourse, or must be willing to use a highly effective birth control upon enrollment, during the treatment period, and for at least 5 months...
- Male patients must not freeze or donate sperm starting at screening and throughout the study period, and for at least 5 months after the final study drug administration.
- Patient must understand, sign and date the written informed consent form (ICF) prior to any protocol-specific procedures performed. Patient should be able and willing to comply with study visits and procedure as per...
- Patient must be affiliated to a social security system or beneficiary of the same
What rules you out
- The following exclusion criteria are applicable for all modules. Patients will be excluded if they present one of them:
- Patient with a breast cancer amenable for resection or radiation therapy with curative intent
- Patient with any history of ILD (including pulmonary fibrosis or radiation pneumonitis), has current ILD, or is suspected to have ILD as assessed by imaging during screening
- Patient with clinically severe pulmonary compromise (based on investigator's assessment) resulting from intercurrent pulmonary illnesses including, but not limited to:
- Any underlying pulmonary disorder (eg, pulmonary embolism, severe asthma, severe chronic obstructive pulmonary disease (COPD), restrictive lung disease, pleural effusion) OR
- Any autoimmune, connective tissue or inflammatory disorder with pulmonary involvement (eg, rheumatoid arthritis, Sjögren's syndrome, sarcoidosis) OR
- Prior pneumonectomy
- Patient receiving chronic systemic corticosteroids dosed at \>10 mg/day prednisone or equivalent anti-inflammatory activity or any form of immunosuppressive therapy prior to Cycle 1 Day 1. Patients who require use of...
- Patient with evidence of any leptomeningeal disease
- Patient with clinically significant corneal disease
- Patient with any evidence of severe or uncontrolled systemic diseases (e.g. active bleeding diatheses, active infection, or psychiatric illness) which in the investigator's opinion makes it undesirable for the patient...
- Evidence of spinal cord compression or brain metastases, defined as being clinically active and symptomatic, or requiring therapy with corticosteroids or anticonvulsants to control associated symptoms. Patients with...
- Inadequate washout period prior to Cycle 1 Day 1, defined as:
- Whole brain radiation therapy or stereotactic brain radiation therapy \<14 days
- Previous treatment with T-DXd \< 28 days
- Any cytotoxic chemotherapy, investigational agents or other anticancer drug(s) from a previous cancer treatment regimen or clinical study \<14 days or 5 half-lives, whichever is longer
- Endocrine therapy \<21 days
- Monoclonal antibodies \<28 days including immune checkpoint inhibitors (ICIs)
- 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
- Live virus vaccination \<28 days
- Prior treatment with an anti-HER3 antibody
- Patients with unresolved toxicities from previous anticancer therapy, defined as toxicities (other than alopecia) not yet resolved to grade ≤1 or baseline, as defined by National Cancer Institute Common Terminology...
- Chemotherapy-induced neuropathy
- Fatigue
- Residual toxicities from prior immuno-oncology treatment: Grade 1 or Grade 2 endocrinopathies provided they are clinically stable and receiving hormone replacement therapy when applicable which may include:
- Hypothyroidism/ hyperthyroidism
- Type I diabetes
- Hyperglycemia
- Adrenal insufficient
- Adrenalitis
- Skin hypopigmentation (vitiligo)
- Has known hypersensitivity to either the drug substances or the inactive ingredients of HER3-DXd and/or T-DXd
- Patient with a history of severe hypersensitivity reactions to other monoclonal antibodies or PARP inhibitors
- Has any malignancy other than locally advanced or ABC within 3 years prior to Cycle 1 Day 1, except adequately resected non-melanoma skin cancer or curatively treated in-situ disease or other curatively treated solid...
- Documented uncontrolled or significant cardiovascular disorder prior to Cycle 1 Day 1, including:
- Corrected QT interval \>450 ms according to Fridericia's formula (QTcF) based on triplicate 12-lead ECGs, approximately 1 minute apart
- LVEF \<45% by either ECHO or MUGA or cardiac MRI if clinically indicated according to the investigator or consulting cardiologist
- Resting systolic blood pressure \>140 mmHg or diastolic blood pressure \>90 mmHg
- Myocardial infarction within 6 months
- Symptomatic congestive heart failure (NYHA class from III to IV)
- Uncontrolled angina pectoris within 6 months
- Cardiac arrhythmia not controlled by ongoing antiarrhythmic treatment
- Diagnosed or suspected long QT syndrome, or known family history of long QT syndrome
- History of clinically relevant ventricular arrhythmias, such as ventricular tachycardia, ventricular fibrillation, or Torsade de Pointes
- Patient has bradycardia of less than 50 bpm (as determined by central reading) unless the subject has a pacemaker
- History of second or third degree heart block. Candidates with a history of heart block may be eligible if they currently have pacemakers, and have no history of fainting or clinically relevant arrhythmia with pacemakers
- Coronary/peripheral artery bypass graft within 6 months
- Complete left bundle branch block
- Active Hepatitis B and/or Hepatitis C infection, such as those with serologic evidence of active viral infection within 28 days of Cycle 1, Day 1. Patients with past or resolved Hepatitis B virus (HBV) infection are...
- Hepatitis B surface antigen (HBsAg) negative and hepatitis B core antibody (anti-HBc) positive; OR
- HBsAg positive and HBV deoxyribonucleic acid (DNA) viral load is documented to be ≤ 2000 IU/mL in the absence of anti-viral therapy and during the previous 12 weeks prior to the viral load evaluation with normal...
- HBsAg positive and HBV DNA viral load is documented to be ≤2000 IU/mL in the absence of anti-viral therapy and during the previous 12 weeks prior to the viral load evaluation with liver metastasis and abnormal...
- Female patient who is pregnant or breastfeeding or intends to become pregnant during the study
- Has a known human immunodeficiency virus (HIV) infection that is not well controlled. All the following criteria are required to define an HIV infection that is well controlled: undetectable viral ribonucleic acid (RNA)...
- 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 patient; alter the...
- Adult under legal protection: guardianship, curatorship, or legal protection; or patient deprived of his/her liberty by a judicial or administrative decision; or patient incapable of giving his/her consent, or patient...
- Participation in another clinical trial evaluating an experimental drug during the last 4 weeks (except non-treatment research) Specific exclusion criteria for each module Module 0: There are no specific exclusion...
- History of hypersensitivity to excipients of olaparib
- Inadequate washout period prior to Cycle 1 Day 1, defined as:
- Strong CYP3A inhibitors \< 1 week
- CYP3A inducers for olaparib and phenobarbital \< 5 weeks and for any other drug \< 3 weeks
The study team makes the final eligibility decision.
Where it's taking place
- Villejuif, France
Questions & answers
Do participants get paid in this trial?
This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.
Is it free to join, and do I need insurance?
Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.
How long does this study last?
The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.
Who can join this trial?
This study is enrolling all sexes, 18 years and older. The study team makes the final eligibility decision.
Where is this trial taking place?
Study sites include Villejuif, France. Enter your location above to see the nearest site and check your eligibility.
Explore other conditions
BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from ClinicalTrials.gov; the study team decides eligibility.