Clinical study to assess the efficacy of U3-1402 in patients with advanced breast cancer with analyzes of biomarkers associated with response to treatment

Phase 1

• Conditions: 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: 21.1Level: LLTClassification code 10072737Term: Advanced breast cancerSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2020-005722-28-FR
• Lead Sponsor: Gustave Roussy

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2021-01-22
• Last Update Posted: 2 September 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 100

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

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 <14 days or stereotactic brain radiation therapy <7 days.
b.Any cytotoxic chemotherapy, investigational agents, or other anticancer drug(s) from a previous cancer treatment regimen or clinical study (other than EGFR TKI), <14 days or 5 half-lives, whichever is longer.
c.Immune checkpoint inhibitor therapy < 21 days.
d.Endocrine therapy < 21 days
e.Major surgery (excluding placement of vascular access) < 28 days.
f.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.
g.Chloroquine or hydroxychloroquine = 14 days.
h.Live virus vaccination <28 days.
10.Prior treatment with an anti-HER3 antibody and/or ADC containing an exatecan derivative that is a topoisomerase I inhibitor (eg, trastuzumab deruxtecan).
11. Patients with grade =2 unresolved toxicities from previous anticancer therapy (other than alopecia), as defined by the NCI-CTCAE version 5.0.
12.Has known hypersensitivity to either the drug substances or inactive ingredients in the drug product.
13.Has any primary malignancy other than locally advanced or metastatic breast cancer within 3 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.
14.Uncontrolled or significant cardiovascular disease prior to Cycle 1 Day 1, including: QT interval corrected by Fridericia's formula (QTcF) prolongation interval of >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

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified