A Study Evaluating the Efficacy and Safety of Multiple Treatment Combinations in Patients With Metastatic or Locally Advanced Breast Cancer

Recruiting now · Phase 1/Phase 2

Conditions studied: Metastatic Breast Cancer

In brief

This is an umbrella study evaluating the efficacy and safety of multiple treatment combinations in participants with metastatic or inoperable locally advanced breast cancer. The study will be performed in two stages. During Stage 1, seven cohorts will be enrolled in parallel in this study: Cohort 1 will consist of programmed death-ligand 1 (PD-L1)-positive participants who have received no prior systemic therapy for metastatic or inoperable locally advanced triple-negative breast cancer (TNBC) (first-line \[1L\] PD-L1+ cohort). Cohort 2 will consist of participants who had disease progression during or following 1L treatment with chemotherapy for metastatic or inoperable locally-advanced TNBC and have not received cancer immunotherapy (CIT) (second-line \[2L\] CIT-naïve cohort). Cohort 3, 5, 6 and 7 will consist of participants with locally advanced or metastatic hormone receptor-positive (HR+), human epidermal growth factor receptor 2 (HER2)-negative disease with one or more PIK3CA mutations. Cohort 4 will consist of participants with locally advanced or metastatic HER2+ /HER2-low disease with one or more PIK3CA mutations who had disease progression on standard-of-care therapies (HER2+ /HER2-low cohort). In each cohort, eligible participants will initially be assigned to one of several treatment arms (Stage 1). During Stage 2, participants in the 2L CIT-naïve cohort who experience disease progression, loss of clinical benefit, or unacceptable toxicity during Stage 1 may be eligible to continue treatment with a different treatment combination, provided Stage 2 is open for enrollment and all eligibility criteria are met.

Key facts

Study ID

NCT03424005

Run by

Hoffmann-La Roche

People needed

1132

Starts

2018-03-30

Expected to finish

2030-09-30

Last updated by the study team

2026-07-15

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Patients must meet all of the following criteria to qualify for Stage 1 (all cohorts) and to qualify for Stage 2 (2L CIT-naïve cohort):
• Age >/= 18 years at the time of signing Informed Consent Form
• Eastern cooperative oncology group (ECOG) performance status of 0 or 1
• Able to comply with the study protocol, in the investigator's judgment
• Metastatic or inoperable locally advanced adenocarcinoma of the breast
• Measurable disease (at least one target lesion) according to RECIST v1.1
• Life expectancy >/= 3 months, as determined by the investigator
• Tumor accessible for biopsy, unless archival tissue is available
• Availability of a representative tumor specimen that is suitable for biomarker analysis via central testing
• Adequate hematologic and end-organ function, defined by the following laboratory test results, obtained within 14 days prior to initiation of study treatment
• For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures and agreement to refrain from breastfeeding and donating eggs, as outlined for each specific treatment arm
• For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating sperm, as outlined for each specific treatment arm

You may not qualify if…

• Exclusion Criteria for Stage 1
• Prior treatment with T-cell co-stimulating or immune checkpoint blockade therapies, including anti-CTLA-4, anti-PD-1, and anti-PD-L1 therapeutic antibodies, CD40 agonists or interleukin-2 (IL-2) or IL-2-like compounds
• Biologic treatment (e.g., bevacizumab) within 2 weeks prior to initiation of study treatment, or other systemic treatment for TNBC within 2 weeks or 5 half-lives of the drug (whichever is longer) prior to initiation of study treatment
• Treatment with systemic immunosuppressive medication (including, but not limited to, corticosteroids, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor alpha agents) within 2 weeks prior to initiation of study treatment, or anticipation of need for systemic immunosuppressive medication during the course of the study
• Eligibility only for the control arm
• Exclusion Criteria for Stage 1 (both cohorts) and Stage 2 (2L CIT-naïve cohort)
• Adverse events from prior anti-cancer therapy that have not resolved to Grade </= 1 or better with the exception of alopecia of any grade and Grade </= 2 peripheral neuropathy
• Treatment with investigational therapy within 28 days prior to initiation of study treatment
• Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently)
• Uncontrolled tumor-related pain
• Symptomatic, untreated, or actively progressing central nervous system (CNS) metastases
• History of leptomeningeal disease
• Active or history of autoimmune disease or immune deficiency
• History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan. History of radiation pneumonitis in the radiation field (fibrosis) is permitted.
• Active tuberculosis
• Severe infection within 4 weeks prior to initiation of study treatment
• Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to initiation of study treatment
• Significant cardiovascular disease
• Prior allogeneic stem cell or solid organ transplantation
• History of malignancy other than breast cancer within 2 years prior to screening, with the exception of those with a negligible risk of metastasis or death
• Pregnancy or breastfeeding, or intention of becoming pregnant during the study

Where it is running

• Asan Medical Center — Seoul, South Korea (enrolling)
• Hadassah University Medical Center — Jerusalem, Israel (enrolling)
• Rabin MC — Petah Tikva, Israel (enrolling)
• Sheba Medical Center — Ramat Gan, Israel (enrolling)
• Tel-Aviv Sourasky Medical Center — Tel Aviv, Israel (enrolling)
• Assuta Medical Centers — Tel Aviv, Israel (enrolling)
• National Cancer Center Clinical Trials Center / Center for Breast Cancer — Goyang-si, South Korea (enrolling)
• Seoul National University Hospital — Seoul, South Korea (enrolling)
• Severance Hospital — Seoul, South Korea (enrolling)
• Samsung Medical Center — Seoul, South Korea (enrolling)
• Hospital Universitario Virgen Macarena — Seville, Sevilla, Spain (enrolling)
• Hospital del Mar — Barcelona, Spain (enrolling)
• Vall d?Hebron Institute of Oncology (VHIO), Barcelona — Barcelona, Spain (enrolling)
• Hospital Universitario Ramon y Cajal — Madrid, Spain (enrolling)
• Centro Integral Oncológico Clara Campal Ensayos Clínicos START — Madrid, Spain (enrolling)
• National Cheng Kung University Hospital — Tainan, Taiwan (enrolling)
• National Taiwan University Hospital — Taipei, Taiwan (enrolling)
• Metro-Minnesota Community Oncology Research Consortium — Saint Paul, Minnesota, United States (enrolling)
• Renown Regional Medical Center — Reno, Nevada, United States (enrolling)
• Tennessee Oncology - Chattanooga Oncology & Hematology Associates — Chattanooga, Tennessee, United States (enrolling)
• The West Clinic — Germantown, Tennessee, United States (enrolling)
• Tennessee Oncology PLLC — Nashville, Tennessee, United States (enrolling)
• Vanderbilt University Medical Center — Nashville, Tennessee, United States (enrolling)
• Peter MacCallum Cancer Centre-East Melbourne — Melbourne, Victoria, Australia (enrolling)
• Fiona Stanley Hospital - Medical Oncology — Murdoch, Western Australia, Australia (enrolling)

Full record on ClinicalTrials.gov

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