Early Human epidermal growth factor receptor 2 (HER2)-positive breast cancer MedDRA version: 20.0 Level: PT Classification code 10006187 Term: Breast cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Sponsors
F. Hoffmann-La Roche Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Age >= 18 years • Ability to comply with the study protocol, in the investigator's judgment • Confirmed diagnosis of HER2-positive breast cancer, and Hormone receptor and programmed death-ligand 1 (PD-L1) status, as documented through central testing of a representative tumor tissue specimen, is required • Primary breast tumor size of > 2 cm by radiographic measurement • Stage at presentation: T2-T4, N1-N3, M0 as determined by American Joint Committee on Cancer staging system, 8th edition • Pathologic confirmation of nodal involvement with malignancy must be determined by fine-needle aspiration or core-needle biopsy. Surgical excision of lymph nodes is not permitted • Patients with multifocal tumors are eligible provided at least one focus is sampled and centrally confirmed as HER2-positive • Patients with multicentric tumors are eligible provided all discrete lesions are sampled and centrally confirmed as HER2-positive • In patients with multifocal or multicentric breast cancer, the largest lesion should be measured to determine T stage • Patient agreement to undergo appropriate surgical management, including axillary lymph node surgery and partial or total mastectomy, after completion of neoadjuvant treatment • Eastern Cooperative Oncology Group Performance Status of 0 or 1 • Baseline left ventricular ejection fraction >= 55% measured by echocardiogram or multiple-gated acquisition scans • Adequate hematologic and end-organ function • Negative HIV test at screening • Negative hepatitis B surface antigen (HBsAg) and negative total hepatitis B core antibody (HBcAb) test at screening, or positive total HBcAb test followed by a negative hepatitis B virus (HBV) DNA test at screening • Negative hepatitis C virus (HCV) antibody test at screening, or positive HCV antibody test followed by a negative HCV RNA test at screening • For women of childbearing potential: agreement to remain abstinent or use contraceptive methods, and agreement to refrain from donating eggs; Women must remain abstinent or use contraceptive methods with a failure rate of =65 years) yes F.1.3.1 Number of subjects for this age range 42
Exclusion criteria
Exclusion criteria: •Prior history of invasive breast cancer•Stage IV (metastatic) breast cancer •Patients with hormone receptor-positive disease will be excluded once approximately 227 patients with hormone receptor-positive disease have been enrolled•Prior systemic therapy for treatment of breast cancer•Previous therapy with anthracyclines or taxanes for any malignancy•Ulcerating or inflammatory breast cancer•Bilateral invasive breast cancer•Undergone incisional and/or excisional biopsy of primary tumor and/or axillary lymph nodes•Sentinel lymph node procedure or axillary lymph node dissection prior to initiation of neoadjuvant therapy•History of other malignancy within 5 years prior to screening, with the exception of those patients who have a negligible risk of metastasis or death, such as adequately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, localized prostate cancer, ductal carcinoma in situ, or Stage I uterine cancer•Cardiopulmonary dysfunction•Dyspnea at rest •Active or history of autoimmune disease or immune deficiency (see protocol)•History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography scan•Active tuberculosis•Major surgical procedure, other than for diagnosis, within 4 weeks prior to initiation of study treatment or anticipation of need for a major surgical procedure during the study•Severe infection within 4 weeks prior to initiation of study treatment, including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia •Treatment with therapeutic antibiotics within 2 weeks (IV antibiotics) or 5 days (oral antibiotics) prior to initiation of study treatment •Prior allogeneic stem cell or solid organ transplantation•Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that contraindicates the use of an investigational drug and may affect the interpretation of the results, or may render the patient at high risk from treatment complications•Treatment with a live, attenuated vaccine within 4 weeks prior to initiation of study treatment, or anticipation of need for such a vaccine during atezolizumab/placebo treatment or within 5 months after the final dose of atezolizumab/placebo•Treatment with investigational therapy within 28 days prior to initiation of study treatment •Prior treatment with CD137 agonists or immune checkpoint blockade therapies, including anti-cytotoxic T lymphocyte-associated protein-4, anti-PD-1, and anti-PD-L1 therapeutic antibodies•Treatment with systemic immunostimulatory agents within 4 weeks or 5 half-lives of the drug (whichever is longer) prior to initiation of study treatment•Treatment with systemic immunosuppressive medication within 2 weeks prior to initiation of study treatment, or anticipation of need for systemic immunosuppressive medication during study treatment •History of severe allergic anaphylactic reactions to chimeric or humanized antibodies or fusion proteins•Known hypersensitivity to Chinese hamster ovary cell products or to any component of the atezolizumab formulation•Known allergy or hypersensitivity to the components of the paclitaxel, cyclophosphamide, or doxorubicin formulations•Known allergy or hypersensitivity to trastuzumab or pertuzumab formulations•Pregnancy or breastfeeding, or intention of becoming pregnant during study treatment or wi
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: • To evaluate the efficacy of atezolizumab + dose-dense anthracycline (doxorubicin) + cyclophosphamide followed by paclitaxel + trastuzumab + pertuzumab [ddAC-PacHP] compared with placebo + ddAC-PacHP in HER2-positive early breast cancer (EBC) in the PD-L1-positive (IC 1/2/3) and the ITT populations on basis of pathological complete response (pCR) (ypT0/is ypN0);Secondary Objective: • To evaluate the efficacy of atezolizumab + ddAC-PacHP compared with placebo + ddAC-PacHP in HER2-positive EBC on basis of pCR based upon hormone receptor status, pCR in the PD L1 negative (IC 0) population and on the basis of event-free survival (EFS), disease-free survival (DFS) and overall survival (OS) • To evaluate patient-reported outcomes (PROs) of function and health-related quality of life (HRQoL) associated with atezolizumab + ddAC-PacHP compared with placebo + ddAC-PacHP, as measured by the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) • To evaluate the safety of atezolizumab + ddAC-PacHP compared with placebo + ddAC-PacHP • To characterize the pharmacokinetic profile of atezolizumab, pertuzumab, trastuzumab, and trastuzumab emtansine • To evaluate the immune response to atezolizumab, trastuzumab, pertuzumab and trastuzumab emtansine • To evaluate pCR, EFS, DFS and OS based upon PIK3CA mutation status;Primary end point(s): 1. pCR in the PD-L1-positive and ITT populations;Timepoint(s) of evaluation of this end point: 1. Up to 54 months | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. pCR (ypT0/is ypN0) based upon hormone receptor status 2. pCR (ypT0/is ypN0) in the PD L1 negative (IC 0) population 3. EFS in all patients and based upon hormone receptor status (ER/PgR positive or ER/PgR negative) and PD-L1 status (IC 0; IC 1/2/3) 4. DFS in all patients who undergo surgery and based upon hormone receptor status (ER/PgR positive or ER/PgR negative) and PD-L1 status (IC 0; IC 1/2/3) 5. OS in all patients and based upon hormone receptor status (ER/PgR positive or ER/PgR negative) and PD-L1 status (IC 0; IC 1/2/3) 6. Mean and mean changes from baseline score in function (role, physical) and global health status (GHS)/ HRQoL by assessment timepoint, and between treatment arms as assessed by the functional and GHS/HRQoL scales of the EORTC QLQ-C30 7. Incidence and severity of adverse events, with severity determined according to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 8. Change from baseline in targeted vital signs 9. Change from baseline in targeted clinical laboratory test results 10. Maximum serum concentration observed [Cmax] and minimum serum concentration under steady-state conditions within a dosing interval [Cmin]) of atezolizumab concentrations in serum at specified timepoints 11. Cmin for pertuzumab, trastuzumab, and trastuzumab emtansinse in serum at specified timepoints 12. Incidence of treatment-emergent anti-drug antibodies (ADAs) to atezolizumab, trastuzumab, pertuzumab, and trastuzumab emtansine 13. pCR (ypT0/is ypN0) based upon PIK3CA mutation status 14. EFS based upon PIK3CA mutation status 15. DFS based upon PIK3CA mutation status 16. OS based upon PIK3CA mutation status;Timepoint(s) of evaluation of this end point: 1-5. Up to 54 months 6. Day 1 of Cycle 1-9, then Day 1 of every other cycle until Cycle 22; at the treatment discontinuation visit (TDV) and in follow-up 7. Up to 54 months 8-9. Baseline to 54 months 10. Day 1 of Cycle 1, 2, 3, 4, 8, | — |
Countries
Brazil, Canada, China, Czechia, Czech Republic, Germany, Italy, Japan, Korea, Republic of, Poland, Russian Federation, Spain, Taiwan, United States
Contacts
Public ContactTrial Information Support Line-TISL
F. Hoffmann-La Roche Ltd
Outcome results
None listed