Patients with human epidermal growth factor receptor 3-overexpressing (HER3-high) and hormone-receptor positive (HR+) advanced breast cancer who have already received standard therapy for HR+ advanced breast cancer (ABC), including only one line of chemotherapy for ABC. MedDRA version: 21.1 Level: LLT Classification code 10072737 Term: Advanced breast cancer System Organ Class: 100000004864
Conditions
Interventions
Product Name: Patritumab Deruxtecan
Product Code: U3-1402
Pharmaceutical Form: Powder for concentrate for solution for injection/infusion
INN or Proposed INN: Patritumab deruxtecan
Other descriptive n
Sponsors
Gustave Roussy
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Female or male patient aged =18 years. 2. Patient with histologically-confirmed HER3-high (=75% of tumor cell membrane positivity at 10x objective) unresectable locally advanced or metastatic on most recent tumor tissue sample available. Tumors have also to be hormone receptor positive (estrogen receptor positive (ER+) and/or, progesterone receptor positive (PR+)) and HER2-neg (IHC2+/ in situ hybridization (ISH) negative or IHC1+ or IHC0+) at the time of the first breast cancer diagnosis. If the tumor was ER+ and/or PR+ at diagnosis and became ER- and/or PR- in the following biopsies, patient can still continue the study. 3. Patient with a documented radiologic unresectable or metastatic progression. 4. Patient may have received anthracyclines and taxanes as (neo) adjuvant treatment (which do not count as a line of treatment) and must have received one line of chemotherapy for ABC, but not more than one line. All patients must be resistant to endocrine therapy and CDK4/6 inhibitors. Previous treatment with PI3K inhibitors, mTOR inhibitors, AKT-inhibitors, poly ADP ribose polymerase (PARP)-inhibitors is allowed. 5. Patient must have metastatic site easily accessible to biopsy (with exception of bone metastasis) and must have accepted to perform pre-treatment, on-treatment and end-of-treatment biopsies. 6. Patient must have at least one radiologically measurable lesion according to response evaluation criteria in solid tumors (RECIST) V1.1 criteria. 7. Patient must have an ECOG PS 0 or 1 at the time of screening. 8. Patient must have a life expectancy =12 weeks. 9. Patient must have adequate bone marrow reserve and organ function, based on local laboratory data within 14 days prior to Cycle 1, Day 1 (...) 10. Female patients of reproductive/childbearing potential 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. Methods considered as highly effective methods of contraception include: • Intrauterine device (IUD) • Intrauterine hormone-releasing system (IUS) • 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. A female is considered of childbearing potential following menarche and until becoming postmenopausal (no menstrual period for a minimum of 12 months) unless permanently sterile (undergone a hysterectomy, bilateral salpingectomy or bilateral oophorectomy) with surgery at least 1 month before the first dose or confirmed by follicle stimulating hormone (FSH) test. 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. 11. If male, the patient must be surgically sterile, must withhold heterosexual intercourse, or must be or willing to use a highly effective birth control upon enrollment, during the treatment period, and for at least 4 months following the last dose of study drug. Male patients 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.
Exclusion criteria
Exclusion criteria: 1. Patient with a breast cancer amenable for resection or radiation therapy with curative intent. 2. 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. 3. Patient with clinically severe pulmonary compromise (...) resulting from intercurrent pulmonary illnesses including, but not limited to: Any underlying pulmonary disorder (...), restrictive lung disease, pleural effusion); Any autoimmune, connective tissue or inflammatory disorder with pulmonary involvement (...); OR prior pneumonectomy. 4. Patient receiving chronic systemic corticosteroids dosed at >10 mg prednisone or equivalent or any form of immunosuppressive therapy prior to Cycle 1 Day 1. Patients who require use of bronchodilators, inhaled steroids, or local steroid injections may be included in the study. 5. Evidence of any leptomeningeal disease. 6. Has clinically significant corneal disease. 7. Any evidence of severe or uncontrolled systemic diseases (...). 8. 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. Patients with clinically inactive or treated brain metastases who are asymptomatic (...) may be included in the study. Patients must have a stable neurologic status for at least 2 weeks prior to Cycle 1 Day 1. 9. Inadequate washout period prior to Cycle 1 Day 1, defined as: a. Whole brain radiation therapy 470 ms for females and >450 ms for males (in electrocardiograms (ECGs) performed at baseline in triplicate, approximately 1 minute apart); Left ventricular ejection fraction (LVEF) <50% by either echocardiogram (ECHO) or cardiac MRI if clinically indicated according to the investigator or consulting cardiologist. 15. Active Hepatitis B and/or Hepatitis C infection, such as those with serologic evidence of viral infection within 28 d
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The main objective of ICARUS-BREAST01 is to evaluate the overall anti-tumor activity of U3-1402, as measured by objective response rate (ORR) based on investigator assessment, in patients with HER3-high (=75% tumor cell membrane staining seen at 10x objective) and HR+ ABC who have progressed on previous standard therapies for HR+ ABC. ;Secondary Objective: 1/ To evaluate the efficacy of U3-1402 in terms of: a.ORR based on centralized review. b.Duration of response (DOR). c.Progression Free Survival (PFS) based on investigator and centralized review. d.Clinical benefit rate (CBR) e.Overall survival (OS) 2/ To evaluate the safety and tolerability of U3-1402, in terms of: a.Frequency and severity of all adverse events (AEs), tTEAEs, SAEs, and adverse events of special interest (AESIs), defined by NCI-CTCAE v5.0 b.Treatment discontinuation, interruptions and dose reductions due to any AEs c.Frequency and severity of laboratory abnormalities defined by NCI-CTCAE v5.0 d.ECG abnormalities (including QT/QTc interval data) and left ventricular ejection fraction (LVEF) decrease (measured by echocardiography (ECHO) or cardiac magnetic resonance imaging (MRI) if indicated) defined by NCI-CTCAE v5.0 Eastern Cooperative Oncology Group performance status [ECOG PS] changes ;Primary end point(s): The primary endpoint is anti-tumor activity of U3-1402, measured by the confirmed ORR. ORR is defined as the proportion of subjects who achieved a confirmed complete response (CR) or partial response (PR) assessed by investigators. Confirmation of response must be demonstrated with an assessment 4 weeks or later from the initial response. Treatment objective response will be radiologically assessed every 6 weeks using RECIST v1.1. ;Timepoint(s) of evaluation of this end point: Every 6 weeks | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. The secondary efficacy endpoints will be evaluated as follows: a. DOR is defined as the time from the date of the first documentation of objective response (CR or PR) to the date of the first documentation of progression (PD) or death due to any cause. Duration of response will be measured for responding subjects (CR or PR) only. b. PFS is defined as the time from date of first dose until the date of the first objective documentation of disease progression or death from any cause, whichever occurs first. For patients without documented radiological progression, follow-up will be censored at the date of last radiological assessment without progression, unless death occurs within 12 weeks following the date of last known progression-free, in which case the death will be counted as a PFS event. c. CBR is defined as the presence of at least a PR or CR, or a stable disease (SD) >6 months. d. OS is defined as the time from date of first dose until death. Patients alive at last follow-up will be censored at this date. 2. Safety and tolerability of U3-1402 will be evaluated continuously through: frequency and severity of any AEs, TEAEs, SAEs, AESIs graded by NCI-CTCAE v5.0; proportion of treatment discontinuations, interruptions, and dose reductions due to any AEs; frequency and severity of laboratory abnormalities defined by NCI-CTCAE v5.0; frequency and severity of QTcF prolongation; LVEF decrease or cardiac dysfunction graded according to NCI-CTCAE v5.0. ;Timepoint(s) of evaluation of this end point: See above | — |
Countries
France
Contacts
Public ContactSponsor Project Manager
Gustave Roussy
Outcome results
None listed