Metastatic breast cancer, including triple negative breast cancer (TNBC), hormone receptor positive breast cancer (HR+ BC), and HER2 positive and HER2 low breast cancer (HER2+/HER2-low BC) MedDRA version: 20.0 Level: PT Classification code 10075566 Term: Triple negative breast cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 23.0 Level: LLT Classification code 10070575 Term: Estrogen receptor positive breast cancer System
Conditions
Interventions
Product Name: Atezolizumab
Product Code: RO551267
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: ATEZOLIZUMAB
Current Sponsor code: RO5541267
Concentration unit: mg/ml
Sponsors
F. Hoffman-La Roche Ltd.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: All cohorts Stage 1 - Age >= 18 years - Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 - Life expectancy>= 3 months - Tumor accessible for biopsy - Availability of a representative tumor specimen that is suitable for determination of Programmed death-ligand 1 and/or additional biomarker status via central testing All cohorts Stage 1 and Stage 2 - Measurable disease according to Response Evaluation Criteria in Solid Tumors 1.1 - Adequate hematologic and end-organ function - For patients receiving therapeutic anticoagulation: stable anticoagulant regimen during the 14 days prior to initiation of study treatment - Negative HIV test, hepatitis B surface antigen at screening, and hepatitis C virus (HCV) antibody test or positive HCV antibody test followed by a negative HCV RNA test at screening - Negative total hepatitis B core antibody (HBcAb) test at screening, or positive total HBcAb test followed by quantitative hepatitis B virus (HBV) DNA = 1%of the tumor area occupied by PD-L1- expressing tumor-infiltrating immune cells of any intensity Hormone Receptor-Positive Cohort Stage 1 - Metastatic or inoperable locally advanced, histologically documented HR+breast cancer, as defined by the ASCO, who had previous lines of treatment for metastatic disease. - Documented ER+tumor according to ASCO/CAP guidelines, defined as >= 1% of tumor cells stained positive based on the most recent tumor biopsy and assessed locally - Documented HER2 negativity determined by a local laboratory - Radiologic/objective evidence of recurrence or progression after the most recent systemic therapy for breast cancer HER2+/HER2 low Cohort Stage 1 - Histologically or cytologically confirmed and documented adenocarcinoma of the breast
Exclusion criteria
Exclusion criteria: All cohorts Stage 1, 2 - Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures, tumor-related pain and uncontrolled or symptomatic hypercalcemia - Symptomatic, untreated, or actively progressing central nervous system metastases. - Symptomatic active lung disease - History of leptomeningeal disease, idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis or tuberculosis on screening and malignancy other than breast cancer within 2 years prior to screening. - History of severe allergic anaphylactic reactions to chimeric or humanized antibodies or fusion proteins - History of autoimmune disease or immune deficiency - Grade >= 3 hemorrhage or bleeding event within 28 days prior to C1D1 - Severe infection within 4 wks prior C1D1 or any active infection - Major surgical procedure within 4wks - Treatment with antibiotics or live, attenuated vaccine within 2 wks or 4wks prior to C1D1 respectively TNBC cohorts Stage 1 - Prior treatment with T-cell co-stimulating or immune checkpoint blockade therapies - Treatment with investigational therapy within 28 days prior to C1D1 - Biologic treatment or other systemic treatment within 2 weeks (wks) prior to C1D1 - Treatment with systemic immunostimulatory agents within 4wks or 5 half-lives of the drug prior to C1D1 - Patients entering Stage 2: immunotherapy-related adverse events that have not resolved to Grade 1 or better or to baseline at the time of consent - Eligibility only for the control arm Stage 1 (2L CIT naïve cohort only) - Prior treatment with capecitabine SGN-LIV1A - Containing arm (Stage 1) - Prior treatment with SGN-LIV1A or MMAE -based biologic - Grade>= 2 neuropathy - Radiotherapy within 2wks prior to C1D1 - AST/ALT > 1.5 x ULN, or 3 x ULN if liver metastases present - Documented history of a cerebrovascular event, unstable angina myocardial infarction, or cardiac symptoms consistent with congestive heart failure, within 6 months prior to study enrollment. Nab-Paclitaxel-Containing Arms (Stage 1) - Grade >= 2 neuropathy related to taxanes Tocilizumab-Containing Arm (Stage 1) - Preexisting CNS demyelinating or seizure disorders - History of diverticulitis, chronic ulcerative lower GI disease, or other symptomatic lower GI conditions that might predispose a patient to GI perforation - Current liver disease unrelated to the underlying cancer diagnosis - Active current infection or history of recurrent bacterial, viral, fungal, mycobacterial, or other infection, including, but not limited to, TB, atypical mycobacterial disease, hepatitis B and C, and herpes zoster, but excluding fungal infections of the nail bed - Active TB as documented by a positive purified protein derivative (PPD) skin test or TB blood test and confirmed by a positive chest X-ray within 3 months prior to initiation of study treatment - Untreated latent TB - History of, or currently active, primary or secondary immunodeficiency Sacituzumab Govitecan- Containing Arm (Stage 1) - Prior treatment with a topoisomerase 1 inhibitor Inavolisib-Containing Arms during Stage 1 - Type 2 diabetes requiring ongoing systemic treatment at the time of study entry; or any history of Type 1 diabetes - Any concurrent ocular or intraocular condition that, in the opinion of the investigator, would require medical or surgical intervention during the study period to prevent or treat vision loss that m
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: - To evaluate the efficacy of treatment combinations during Stage 1 based on objective response rate (ORR) - To evaluate the safety of treatment combinations during Stage 1 based on Incidence, nature, and severity of adverse events and laboratory abnormalities, with severity determined according to NCI CTCAE v4.0, changes from baseline in vital signs and ECG parameters and change from baseline in targeted clinical laboratory test results.;Secondary Objective: - To evaluate the efficacy of treatment combinations during Stage 1 based on progression-free survival (PFS), disease control rate (DCR), overall survival (OS), OS at specific timepoints and duration of response (DOR;Primary end point(s): 1. ORR Stage 1 and 2 1. Incidence, nature, and severity of adverse events and laboratory abnormalities, with severity determined according to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 2. Change from baseline in vital signs and electrocardiogram parameters 3. Change from baseline in targeted clinical laboratory test results 4. Plasma or serum concentration of each drug at specified timepoints 5. For drugs for which anti-drug antibody (ADA) formation is measured: presence of ADAs during the study relative to the presence of ADAs at baseline;Timepoint(s) of evaluation of this end point: Stage 1 1.up to 8 years Stage 1 and 2 1-3. up to 8 years 4-5. Atezo+Nab-Pac Arm: Atezo: D1 of C1-4, 8, 12, 16; Atezo + SGN-LIV1A arm: SGN-LIV1A: D1, 8, 15 of C1; D1, of C1, 3, 4, 8, 12 and 16 ; Atezo+Nab-Pac+TCZ Arm: D1 of C1-4, 6, 8, 10, 12, 14, 16; Atezo+SG Arm: D1 of C1-5, 7,8, 9, 11, 12-16; Inavo+Abema+Fulv Arm and Inavo + Ribo + Fulv Arm: D1 and D15 of C1, D1 of C2; T-DXd+ Inavo Arms: D1 and D15 of C1; at treatment discontinuation visit (for all arms) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. PFS 2. DCR 3. OS 4. DOR 5. OS at specific timepoints ;Timepoint(s) of evaluation of this end point: 1-4. up to 8 years 5. Every year up to 8 years | — |
Countries
Australia, European Union, France, Germany, Korea, Republic of, Spain, United Kingdom, United States
Contacts
Public ContactTrial Information Support Line-TISL
F.Hoffmann-La Roche Ltd.
Outcome results
None listed