A Study of Atezolizumab Plus Nab-Paclitaxel in the Treatment of Unresectable Locally Advanced or Metastatic PD-L1-Positive Triple-Negative Breast Cancer

Study Overview
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Brief Summary
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Study MO39874 is an open-label, Phase IIIb, single arm, global study conducted in participants with unresectable locally advanced or metastatic PD-L1-positive Triple-Negative Breast Cancer (TNBC) who have not received chemotherapy for their unresectable locally advanced or metastatic disease.

Official Title
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An Open-Label, Phase IIIb, Single Arm, Multicenter Safety Study of Atezolizumab (Tecentriq) Plus Nab-Paclitaxel in the Treatment of Unresectable Locally Advanced or Metastatic Triple-Negative Breast Cancer

Conditions
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Triple-Negative Breast Cancer

Intervention / Treatment
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* Drug: Atezolizumab
* Drug: Nab-Paclitaxel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Unresectable locally advanced or metastatic, histologically documented TNBC (negative for HER2 and ER and PgR) At least one specimen positive for PD-L1 status as determined by VENTANA PD-L1 SP142 IHC Assay No prior chemotherapy, experimental or targeted systemic therapy for unresectable locally advanced or metastatic TNBC Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2 Life expectancy ≥ 12 weeks Measurable disease, as defined by RECIST v1.1 Adequate haematologic and end-organ function, defined by the following laboratory results obtained within 14 days prior to the initiation of study treatment Negative hepatitis B surface antigen (HBsAg) test at screening Negative total hepatitis B core antibody (HBcAb) test at screening, 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 at screening, or positive HCV antibody test followed by a negative HCV ribonucleic acid (RNA) test at screening Patients with treated asymptomatic central nervous system (CNS) metastases are eligible, provided that all the following criteria are met: (a) The metastases are limited to the supratentorial region or cerebellum (b) No ongoing requirement for corticosteroids as therapy for CNS disease (c) No stereotactic radiation within 7 days or whole-brain radiation or neurosurgical resection within 2 weeks before the start of study treatment (d) Radiographic demonstration of interim stability between the completion of CNS-directed therapy and the screening imaging study. Patients with a history of autoimmune disease (Appendix 2) are allowed if controlled and on stable treatment (i.e., same treatment, same dose) for the last 12 weeks For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) 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: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures and agreement to refrain from donating sperm Women who are not postmenopausal (≥ 12 months of non-therapy-induced amenorrhea) or surgically sterile must have a negative serum pregnancy test result within 14 days prior to initiation of study drug 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 (Cycle 1, Day 1). Leptomeningeal carcinomatosis or any symptomatic CNS metastases Uncontrolled symptomatic pleural effusion, pericardial effusion, or ascites Uncontrolled tumour-related pain Uncontrolled hypercalcemia (> 1.5 mmol/L ionized calcium or calcium > 12 mg/dL or corrected serum calcium > ULN) or symptomatic hypercalcemia requiring continued use of bisphosphonate therapy. Malignancies other than breast cancer within 5 years prior to the first dose of study treatment (Cycle 1, Day 1), 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 (NYHA) cardiac disease (Class II or greater), myocardial infarction within 3 months prior to the first dose of study treatment (Cycle 1, Day 1), unstable arrhythmias, or unstable angina Severe infection within 4 weeks prior to the first dose of study treatment (Cycle 1, Day 1), including but not limited to hospitalization for complications of infection, bacteraemia, or severe pneumonia, or any active infection, that in the opinion of the investigator, could impact patient safety. Treatment with oral or IV antibiotics within 2 weeks prior to initiation of study treatment (Cycle 1, Day 1) Major surgical procedure within 28 days prior to the first dose of study treatment (Cycle 1, Day 1), or anticipation of the need for a major surgical procedure during the course of the study (other than diagnostic procedures) 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 (HIV) test at screening, unless the patient meets all of the following conditions: stable on anti-retroviral therapy, CD4 count ≥200/mL, undetectable viral load 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 to 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 (including pneumonitis), drug-induced pneumonitis, organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia), or evidence of active pneumonitis on screening chest CT 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 (Cycle 1, Day 1), or anticipation that such a live, attenuated vaccine will be required during atezolizumab treatment or within 5 months following the final dose of atezolizumab Prior treatment with CD137 agonists or immune checkpoint blockade therapies (including anti-CTLA4 antibodies), except for anti-PD-1 or anti-PD-L1 antibodies. Treatment with systemic immunostimulatory agents (including but not limited to interferons or IL-2) within 4 weeks or five half-lives of the drug (whichever is longer) prior to the first dose of study treatment (Cycle 1, Day 1) Only in patients without autoimmune disease: Treatment with systemic corticosteroids or other systemic immunosuppressive medications (including but not limited to prednisone, dexamethasone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and antitumour necrosis factor [TNF] agents) within 2 weeks prior to the first dose of study treatment (Cycle 1, Day 1), or anticipated requirement for systemic immunosuppressive medications during the study

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: This is an open-label (non-blinded), single arm safety study in which all participants will receive atezolizumab in combination with nab-paclitaxel.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Atezolizumab plus Nab-Paclitaxel<br>Participants will receive Atezolizumab via intravenous (IV) infusion on Days 1 and 15 of every 28-day cycle in combination with Nab-Paclitaxel on Days 1, 8, and 15 (individually selected by the investigator) until disease progression, or unacceptable toxicity, additionally until loss of clinical benefit as determined by the investigator or participant decision to discontinue treatment. | Drug: Atezolizumab<br>* Atezolizumab will be administered at a dose of 840 mg via IV infusion on Days 1 and 15 of every 28-day cycle. Day 15: Atezolizumab may be administered on Days 15-18 of each cycle.<br>* Other names: Tecentriq;Drug: Nab-Paclitaxel<br>* Nab-Paclitaxel will be administered at the 100 mg/m2 dose via IV infusion on Days 1, 8, and 15 of every 28-day cycle. Day 8: Nab-paclitaxel may be administered on Days 8-11 of each cycle. Day 15: Nab-paclitaxel may be administered on Days 15-18 of each cycle, on the same day with the atezolizumab infusion.<br>* Other names: Abraxane;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants with treatment-emergent Grade≥3 AEs |  | From baseline to up to 4.5 years | 
| Percentage of Participants with treatment-emergent Grade≥2 imAEs |  | From baseline to up to 4.5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants with all treatment-emergent AEs |  | From baseline to up to 4.5 years | 
| Percentage of Participants with treatment-emergent SAEs |  | From baseline to up to 4.5 years | 
| Overall survival (OS) in ITT Population | OS defined as the time from initiation of study treatment to death from any cause. | From baseline to 4.5 years | 
| Overall survival (OS) in PD-L1-Positive Tumor Status Population | OS defined as the time from initiation of study treatment to death from any cause. | From baseline to 4.5 years | 
| Progression Free Survival (PFS) in ITT Population | PFS defined as the time from initiation of study treatment to the first occurrence of disease progression or death from any cause, whichever occurs first. PFS will be assessed by the investigator according to RECIST v1.1. | From baseline to 4.5 years | 
| Progression Free Survival (PFS) in PD-L1-Positive Tumor Status Population | PFS defined as the time from initiation of study treatment to the first occurrence of disease progression or death from any cause, whichever occurs first. PFS will be assessed by the investigator according to RECIST v1.1. | From baseline to 4.5 years |