Pre- and post-menopausal women or men with advanced (loco-regionally recurrent not amenable to curative therapy or metastatic) HER2-positive breast cancer who have progressed to trastuzumab based chemotherapy and AntiHER2-ADC.

Phase 1

• Conditions: Pre- and post-menopausal women or men with advanced (loco regionally recurrent not amenable to curative therapy or metastatic)HER2-positive breast cancer who have progressed to trastuzumab based chemotherapy and AntiHER2-ADC; Therapeutic area: Diseases [C] - Neoplasms [C04]

• Registration Number: CTIS2023-508829-28-00
• Lead Sponsor: Solti Group

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2024-07-22
• Last Update Posted: 21 August 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 55

Inclusion Criteria

Patient eligibility will be reviewed and documented by a suitable member of the Investigator’s study team before the patients are enrolled in the study (section 6.2.2) Any asterisked* are also applicable as an exclusion criterion prior to perform the prescreening PAM50 testing. To perform the PAM50 assay, investigator judgement of patient’s potential eligibility to the study should be assessed as per Table of assessments (section 6.1). All the following criteria must be fulfilled for a patient to be eligible to this study: 1. Written signed Informed Consent for all study procedures in accordance with the local administrative requirements prior to starting the protocol-specific procedures., *Baseline LVEF =50% measured using echocardiogram or equilibrium isotopic ventriculography (MUGA)., *Absence of psychological, family, sociological or geographical conditions that could potentially hinder compliance with the study protocol and follow-up schedule. These situations must be discussed with the patient before she is included in the study., If female of childbearing potential, must have a negative result of serum pregnancy test performed within 7 days prior to first dose of study treatment. Females of childbearing age potential and male subjects with partners of childbearing potential must use highly effective (Appendix H) contraceptive measures (according to CTFG recommendations). According to the clinical trial facilitation group recommendations, a woman is considered of childbearing potential (WOCBP), i.e. fertile, following menarche and until becoming post-menopausal unless permanently sterile. Permanent sterilisation methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. Subjects should be informed and accept that these requirements should also extend to: - 5 months after the last dose with Atezolizumab, - 3 months after the last dose with Vinorelbine and - 7 months after the last dose with Trastuzumab., Participants with a history of CNS metastases are eligible, must have one of the following: - Untreated brain metastases not needing immediate local therapy. For patients with untreated CNS lesions > 2.0 cm on screening contrast brain MRI, discussion with and approval from the medical monitor is required prior to enrollment. - Previously treated brain metastases: a) Brain metastases previously treated with local therapy may either be stable since treatment or may have progressed since prior local CNS therapy, provided that there is no clinical indication for immediate re-treatment with local therapy in the opinion of the investigator. b) Patients treated with CNS local therapy for newly identified lesions may be eligible to enroll if all of the following criteria are met: i) Time since WBRT is = 21 days prior to first dose of treatment, time since SRS is = 7 days prior to first dose of treatment, or time since surgical resection is = 21 days. ii) Other sites of disease assessable by RECIST 1.1 are present., *Male or female patients. Premenopausal or postmenopausal women., *Age 18 years or older, *ECOG performance status 0 to 2 (Appendix A)., *Histologically confirmed adenocarcinoma of the breast, metastatic or unresectable locally advanced. a. Patients with locally advanced disease must have recurrent or progressive disease unsuitable for resection with curative intent. Patients with standard curative opt

Exclusion Criteria

Treatment with any investigational anticancer drug within 14 days of the start of study treatment., Major surgery in the 28 days prior to enrolment or foreseeable during study treatment period., *Infection with HIV or active Hepatitis B and/or Hepatitis C., *History of trastuzumab intolerance, including grade 3-4 infusion reaction or hypersensitivity., *Known hypersensitivity or allergy to biopharmaceuticals produced in Chinese hamster ovary (CHO) cells or any component of the atezolizumab formulation, *History of autoimmune disease, including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjogren's syndrome, Guillain-Barré syndrome, multiple sclerosis , vasculitis, or glomerulonephritis. (Note: Patients with a history of autoimmune-related hypothyroidism on a stable dose of thyroid replacement hormone and patients with controlled Type 1 diabetes mellitus on a stable insulin regimen may be eligible for this study.), *Prior allogeneic stem cell or solid organ transplantation, *History of idiopathic pulmonary fibrosis (including pneumonitis), drug-induced pneumonitis, organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia), or evidence of active pneumonitis on screening chest CT scan. (Note: History of radiation pneumonitis in the radiation field [fibrosis] is permitted.), *Active tuberculosis, Receipt of a live, attenuated vaccine within 4 weeks prior to enrolment or anticipation that such a live, attenuated vaccine will be required during the study. Note: Patients must agree not to receive live, attenuated influenza vaccine (e.g., FluMist®) within 28 days prior to enrolment, during treatment or within 5 months following the last dose of atezolizumab, *Prior treatment with CD137 agonists, anti-PD-1, or anti-PD-L1 therapeutic antibody or immune checkpoint targeting agents, Patient who has received Vinorelbine or any other vinca alkaloids immediately prior to initiate study treatment are excluded. Patients previously treated with vinorelbine or other vinca alkaloids that afterwards have received at least a subsequent treatment line with a permitted regimen can be enrolled., Treatment with systemic immunostimulatory agents (including but not limited to interferons or interleukin [IL]-2) within 4 weeks or five half-lives of the drug (whichever is longer) prior to enrolment, *Treatment with systemic immunosuppressive medications (including but not limited to corticosteroids, cyclophosphamide, azathioprine, cyclosporine, methotrexate, thalidomide, and antitumor necrosis factor [TNF] agents) within 2 weeks prior to enrolment, or anticipated requirement for systemic immunosuppressive medications during the trial. a. Patients who have received acute, low-dose (= 10 mg oral prednisone or equivalent), systemic immunosuppressant medications may be enrolled in the study. b. Patients with a history of allergic reaction to IV contrast requiring steroid pre-treatment should have baseline and subsequent tumor assessments performed using MRI. c. The use of corticosteroids (= 10 mg oral prednisone or equivalent) for chronic obstructive pulmonary disease, mineralocorticoids (e.g., fludrocortisone) for patients with orthostatic hypotension, and low dose supplemental corticosteroids for adrenocortical insufficiency are allowed., *Inability

Study & Design

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