Comparing 3 approaches for breast neoplasms

Inclusion

• +i) InvestigatorPrincipal investigatorThe doctor or researcher responsible for running the study at a site.Read more →-determined ineligibility based on PD-L1 negative disease determined and documented prior to trial screeningScreeningThe checks done before joining, to see whether a study fits.Read more → as part of standard of careStandard of careThe treatment normally given for a condition outside a study.Read more → (SoC); ii) Has experienced disease relapse between 6 to 12 months after the completion of (neo)adjuvant therapy with an anti-PD(L)1; iii) Has a severe auto-immune disease or other contraindication, in the opinion of the investigator, for the use of an anti-PD(L)1 drug: iv) Any auto-immune disease that requires current immunosuppression (eg, methotrexate, cyclophosphamide, prednisone \> 10 mg/day).
• +Untreated symptomatic central nervous system (CNS) metastases. Participants are eligible if CNS metastases have been treated, and participants' neurological signs and symptoms have returned to baselineBaselineYour starting measurements, taken before treatment begins.Read more →. In addition, participants must have been either off corticosteroids, or on a stable or decreasing dose of ≤ 10 mg daily prednisone (or equivalent) for at least 2 weeks prior to randomizationRandomisedWhich group you go into is decided by chance, not by you or your doctor.Read more →. Imaging performed within 28 days of randomization must document radiographic stability of CNS lesions and be performed after completion of any CNS directed therapy.
• +Leptomeningeal metastases.
• +vii) Current or prior auto-immune diseases per below: A. Moderate to severe rheumatoid arthritis. B. Auto-immune hepatitis or cholangitis. C. Myasthenia gravis. D. Moderate-to-severe or poorly controlled inflammatory bowel disease. E. Multiple sclerosis. F. Lupus with kidney involvement or moderate to severe lupus. G. Auto-immune myocarditis. Note: if participant meets Inclusion CriteriaInclusion criteriaThe things you must have or be for a study to consider you.Read more → 5b or 5c, unknown PDL1 results per local SOC are acceptable in these specific cases.
• +Histologically or cytologically confirmed and documented locally-advanced, recurrent inoperable, or metastatic triple-negative breast cancer (TNBC) (ER \< 1%, PgR \< 1%, HER2 IHC 0, 1+, or 2+ with ISH negative for HER2 gene amplification) or ER-low, HER2-negative BC (ER and / or PgR 1% to 10%, HER2 IHC 0, 1+, or 2+ with ISH negative for HER2 gene amplification) per American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) criteria, based on the most recently analyzed biopsy or other pathology specimen.
• +Patients with recurrent disease must have experienced disease relapse at least 6 months after finishing their last therapy with curative intent.
• +v) Prior auto-immune AEAdverse eventAny medical problem that happens during a study, whether or not the treatment caused it.Read more → to peri-adjuvant ICI that required immunosuppression. vi) Current Graves' disease with ophthalmopathy or in need of radioiodine or in use of antithyroid medication.
• +Patients with ER-low, HER2-negative BC must be ineligible, in the opinion of the Investigator, for endocrine therapy-based treatments.
• +No previous systemic therapy in the locally advanced, recurrent inoperable or metastatic setting (ie incurable setting).
• +Measurable disease by CT or MRI as per RECIST v1.1.
• +Exclusion CriteriaExclusion criteriaThe things that would prevent someone from taking part.Read more →
• +Participants with a known germline breast cancer gene (BRCA) 1 or 2 mutation whose best 1L treatment option, in the opinion of the investigator, is a poli-ADP-ribose-polymerase inhibitors (PARPi).
• +Participants with history of severe heart disease including, but not limited to, any of the following:
• +i) History of clinically significant heart disease (eg, cardiomyopathy, congestive heart failure with New York Heart Association functional classification II to IV, pericarditis, or significant pericardial effusion).
• +ii) Myocardial infarction, uncontrolled angina, or stroke/transient ischemic attack within the past 6 months.
• +iii) QTc (by Fridericia's formula) prolongation ≥ 450 msec for males and ≥ 470 msec for females, except for right bundle branch block.
• +iv) Known LVEF \< 50%.
• +Prior therapy with iza-bren or any other ADC targeting EGFR and/or HER3 or containing a topoisomerase 1 inhibitor payload.
• +Other protocolProtocolThe detailed plan a study must follow.Read more →-defined Inclusion/Exclusion criteria apply.
• +Participants with TNBC must be considered ineligible for 1L chemotherapy combination treatment with an anti-PD-1 (eg, pembrolizumab) or an anti-PD-L1 (eg, atezolizumab) due to any one of the following criteria: