| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Unresectable locally advanced or metastatic triple-negative breast cancer (TNBC) |
|
| E.1.1.1 | Medical condition in easily understood language |
| TNBC refers to breast cancer that does not express the genes for estrogen and progesterone receptors and Human epidermal growth receptor 2 |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 20.0 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10075566 |
| E.1.2 | Term | Triple negative breast cancer |
| E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| • To evaluate the safety of atezolizumab when given in combination with nab-paclitaxel/ paclitaxel in patients with unresectable locally advanced or metastatic Programmed death-ligand 1 (PD-L1)-positive TNBC who have not received prior systemic cytotoxic therapy for locally advanced or metastatic TNBC on basis of incidence of treatment-emergent Grade >=3 adverse events (AEs) and Grade >=2 Immune-mediated adverse events (imAEs) |
|
| E.2.2 | Secondary objectives of the trial |
• To further evaluate the safety of atezolizumab when given in combination with nab-paclitaxel/ paclitaxel in patients with unresectable locally advanced or metastatic PD-L1-positive TNBC who have not received prior systemic cytotoxic therapy for locally advanced or metastatic TNBC on basis of all treatment-emergent AEs and serious adverse events (SAEs)
• To evaluate the effect of atezolizumab plus nab-paclitaxel/ paclitaxel on key survival outcomes in patients with unresectable locally advanced or metastatic PD-L1-positive TNBC who have not received prior systemic cytotoxic therapy for locally advanced or metastatic TNBC on basis of overall survival and progression-free survival
|
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
- Female or male >=18 years
- Ability to comply with the study protocol, in the investigator’s judgment
- Patients with unresectable locally advanced or metastatic, histologically documented TNBC (negative for HER2 and ER and PgR)
- Patient with at least one specimen positive for PD-L1 status as determined by VENTANA PD-L1 SP142 Assay
o Specimens with PD-L1 expression on tumor-infiltrating immune cells (IC) covering >=1% of tumor area would be PD-L1 positive, whereas PD-L1 expression on IC covering <1% of tumor area would be PD-L1 negative
o PD-L1-positive tumour status. If multiple tumour specimens are available, patients may be eligible if at least one specimen is evaluable for PD-L1 testing and shows PD-L1 expression on >=1% IC
o PD-L1-positive tumour status (PD-L1 expression >=1% on tumour-infiltrating ICs as percentage per tumour area, assessed by IHC). If multiple tumour specimens are available, patients may be eligible if at least one specimen is evaluable for PD-L1 testing and shows PD-L1 expression on >=1% IC
o Acceptable samples include core needle biopsies for deep tumour tissue or excisional, incisional, punch, or forceps biopsies for cutaneous, subcutaneous, or mucosal lesions
o Fine needle aspiration, brushing, cell pellet from pleural effusion, bone metastases, and lavage samples are not acceptable
o Tumour tissue from bone metastases is not evaluable for PD-L1 expression and is therefore not acceptable
- No prior chemotherapy, experimental or targeted systemic therapy for unresectable locally advanced or metastatic TNBC
- Eastern Cooperative Oncology Group performance status of 0, 1 or 2
- Life expectancy >=12 weeks
- Measurable disease, as defined by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1)
- Adequate haematologic and end-organ function within 14 days prior to the initiation of study treatment
- Negative hepatitis B surface antigen test at screening
- Negative total hepatitis B core antibody (HBcAb) test, or positive HBcAb test followed by a negative hepatitis B virus (HBV) deoxyribonucleic acid (DNA) test at screening
- Negative hepatitis C virus (HCV) antibody test or positive HCV antibody test followed by a negative HCV ribonucleic acid (RNA) test at screening
- Patients with asymptomatic central nervous system (CNS) metastases are eligible
- Patients with a history of autoimmune disease are allowed if controlled and on stable treatment for the last 12 weeks
- For women of childbearing potential: agreement to remain abstinent or use contraceptive methods that result in a failure rate of < 1% per year, during the treatment period and for at least 5 months after the last dose of atezolizumab or 6 months after the last dose of nab-paclitaxel/paclitaxel, whichever is later. In addition, women must refrain from donating eggs during the same time period
- For men: with female partners of childbearing potential or pregnant female partners, men must remain abstinent or use a condom during the treatment period and for at least 6 months after the last dose of any component of the study treatment. Men must refrain from donating sperm during this same period
- Women who are not postmenopausal or surgically sterile must have a negative serum pregnancy test result within 14 days prior to initiation of study drug
|
|
| E.4 | Principal exclusion criteria |
Cancer-Specific Exclusion Criteria
- Spinal cord compression not definitively treated with surgery and/or radiation, or previously diagnosed and treated spinal cord compression without evidence that disease has been clinically stable for > 2 weeks prior to the first dose of study treatment
- Leptomeningeal carcinomatosis or any symptomatic CNS metastases
- Uncontrolled symptomatic pleural effusion, pericardial effusion, or ascites
- Uncontrolled tumour-related pain and hypercalcemia
- Malignancies other than TNBC within 5 years prior to the first dose of study treatment, with the exception of those with a negligible risk of metastasis or death and treated with expected curative outcome
General Medical Exclusion Criteria:
- Pregnancy or lactation
- Evidence of significant uncontrolled concomitant disease that could affect compliance with the protocol or interpretation of results, including significant liver disease
- Significant cardiovascular disease such as New York Heart Association cardiac disease, myocardial infarction within 3 months prior to the first dose of study treatment, unstable arrhythmias, or unstable angina
- Severe infection within 4 weeks prior to the first dose of study treatment, including but not limited to hospitalization for complications of infection, bacteremia, or severe pneumonia
- Treatment with oral or IV antibiotics within 2 weeks prior to initiation of study treatment
- Major surgical procedure within 28 days prior to the first dose of study treatment, or anticipation of the need for a major surgical procedure during the course of the study
- Treatment with investigational therapy within 4 weeks prior to Cycle 1, Day 1
- Known hypersensitivity to nab-paclitaxel or any of the excipients, when nab-paclitaxel is used as a backbone taxane
- Known hypersensitivity to paclitaxel or any of the excipients, when paclitaxel is used as a backbone taxane
- Positive human immunodeficiency virus test at screening
- Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that contraindicates the use of an investigational drug, may affect the interpretation of the results, or may render the patient at high risk from treatment complications
Exclusion Criteria Related to Atezolizumab
- History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
- Known hypersensitivity or allergy tbco biopharmaceuticals produced in Chinese hamster ovary cells or any component of the atezolizumab formulation
- Prior allogenic stem cell or solid organ transplantation
- History of idiopathic pulmonary fibrosis, drug-induced pneumonitis, organizing pneumonia, or evidence of active pneumonitis on screening chest computed tomography scan
- Current treatment with anti-viral therapy for HBV
- Active tuberculosis
- Receipt of a live, attenuated vaccine within 4 weeks prior to the first dose of study treatment, or anticipation that such a live, attenuated vaccine will be required during the study
- Prior treatment with CD137 agonists or immune checkpoint blockade therapies, including anti-CTLA4 antibodies
- Treatment with systemic immunostimulatory agents within 4 weeks or five half-lives of the drug prior to the first dose of study treatment
- Only in patients without autoimmune disease: Treatment with systemic corticosteroids or other systemic immunosuppressive medications within 2 weeks prior to the first dose of study treatment, or anticipated requirement for systemic immunosuppressive medications during the study
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
1. Incidence of treatment-emergent Grade >=3 AEs
2. Incidence of treatment-emergent Grade >=2 imAEs
|
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| 1-2. Up to 30 days after the last dose of study treatment |
|
| E.5.2 | Secondary end point(s) |
1. Incidence of all treatment-emergent AEs
2. Incidence of treatment-emergent SAEs
3. Overall survival
4. Progression-free survival
|
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
1-2. Up to 30 days after the last dose of study treatment
3-4. Up to 4 years
|
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | No |
| E.8.1.1 | Randomised | No |
| E.8.1.2 | Open | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | No |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 1 |
| E.8.3 |
The trial involves single site in the Member State concerned
| Information not present in EudraCT |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Information not present in EudraCT |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 10 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 73 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | No |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Yes |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
| Argentina |
| Chile |
| China |
| Czech Republic |
| France |
| Germany |
| Italy |
| Mexico |
| Peru |
| Poland |
| Portugal |
| Romania |
| Slovakia |
| Slovenia |
| Spain |
|
| E.8.7 | Trial has a data monitoring committee | No |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 4 |
| E.8.9.1 | In the Member State concerned months | 1 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 4 |
Print
