A Study of the Efficacy and Safety of Atezolizumab Plus Chemotherapy for Patients With Early Relapsing Recurrent Triple-Negative Breast Cancer

• Register: ClinicalTrials.gov
• Last refreshed on: 11 March 2024
• Main ID: NCT03371017
• Date of registration: 21/11/2017
• Prospective Registration: Yes
• Primary sponsor: Hoffmann-La Roche
• Public title: A Study of the Efficacy and Safety of Atezolizumab Plus Chemotherapy for Patients With Early Relapsing Recurrent Triple-Negative Breast Cancer IMpassion132
• Scientific title: A Phase III, Randomised, Double-Blind, Placebo-Controlled, Multicentre Study Of The Efficacy And Safety Of Atezolizumab Plus Chemotherapy For Patients With Early Relapsing Recurrent (Inoperable Locally Advanced Or Metastatic) Triple-Negative Breast Cancer
• Date of first enrolment: January 11, 2018
• Target sample size: 572
• Recruitment status: Active, not recruiting
• URL: https://clinicaltrials.gov/ct2/show/NCT03371017
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor).
• Phase: Phase 3

Countries of recruitment

Algeria, Argentina, Bosnia and Herzegovina, Brazil, Chile, China, Cuba, Egypt, Finland, France, Germany, Hungary, Italy, Kazakhstan, Korea, Republic of, Mexico, Montenegro, Morocco, Panama, Peru, Poland, Portugal, Russian Federation, Serbia, Singapore, South Africa, Spain, Turkey, United Kingdom, United States

Contacts

• Name: Clinical Trials
• Affiliation: Hoffmann-La Roche

Key inclusion & exclusion criteria

Inclusion Criteria:

- Histologically confirmed triple negative breast cancer (TNBC) that is either locally
recurrent, inoperable and cannot be treated with curative intent or is metastatic

- Documented disease progression occurring within 12 months from the last treatment with
curative intent

- Prior treatment (of early breast cancer) with an anthracycline and taxane

- Have not received prior chemotherapy or targeted systemic therapy for their locally
advanced inoperable or metastatic recurrence. Prior radiation therapy for recurrent
disease is permitted

- Measurable or non-measurable disease, as defined by RECIST 1.1

- Availability of a representative formalin-fixed, paraffin-embedded (FFPE) tumour block
(preferred) or at least 17 unstained slides obtained from relapsed metastatic or
locally advanced diseases may be submitted, if clinically feasible, with an associated
pathology report, if available. If a fresh tumour sample is not clinically feasible,
either the diagnosis sample, the primary surgical resection sample, or the most recent
FFPE tumour biopsy sample should be used.

- Eastern Cooperative Oncology Group performance status 0-1

- Life expectancy = 12 weeks

- Adequate haematologic and end-organ function

- Negative human immunodeficiency virus (HIV) test ---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) DNA test at screening

- The HBV DNA test will be performed only for patients who have a negative HBsAg and a
positive HBcAb test.

- Negative hepatitis C virus (HCV) antibody test at screening, or positive HCV antibody
test followed by a negative HCV RNA test at screening.

- Women of childbearing potential must agree to remain abstinent (refrain from
heterosexual intercourse) or use a contraceptive method with 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 capecitabine, whichever is later. In
addition, women must refrain from donating eggs during the same time period.

- Men must agree to remain abstinent (refrain from heterosexual intercourse) or use
contraceptive measures, and agree to refrain from donating sperm

Inclusion criteria for patients enrolled after the recruitment of all-comers is complete:

-PD-L1-positive tumour status (assessed centrally prior to randomisation), defined as PD-L1
expression on tumour-infiltrating immune cells (IC) of 1% or greater.

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 randomisation

- Symptomatic, untreated, or actively progressing central nervous system (CNS)
metastases.

- Symptomatic or rapid visceral progression

- No prior treatment with an anthracycline and taxane

- History of leptomeningeal disease

- Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent
drainage procedures (once monthly or more frequently) (patients with indwelling
catheters such as PleurX® are allowed)

- Uncontrolled tumour-related pain

- Uncontrolled or symptomatic hypercalcemia

- Malignancies other than TNBC within 5 years prior to randomisation)

- Significant cardiovascular disease, within 3 months prior to randomisation, unstable
arrhythmias, or unstable angina

- Presence of an abnormal ECG

- Severe infection requiring oral or IV antibiotics within 4 weeks prior to
randomisation, including but not limited to hospitalization for complications of
infection, bacteraemia, or severe pneumonia.

- Current treatment with anti-viral therapy for HBV.

- Major surgical procedure within 4 weeks prior to randomisation or anticipation of the
need for a major surgical procedure during the course of the study other than for
diagnosis

- Treatment with investigational therapy within 28 days prior to randomisation

- Pregnant or lactating, or intending to become pregnant during or within 5 months after
the last dose of atezolizumab, or within 6 months after the last dose of capecitabine,
whichever is later.

Exclusion Criteria Related to Atezolizumab:

- History of severe allergic, anaphylactic, or other hypersensitivity reactions to
chimeric or humanised antibodies or fusion proteins

- Known hypersensitivity or allergy to biopharmaceuticals produced in Chinese hamster
ovary cells or to any component of the atezolizumab formulation

- History of autoimmune disease

- Prior allogeneic 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
computerised tomography (CT) scan History of radiation pneumonitis in the radiation
field (fibrosis) is permitted.

- Active tuberculosis

- Receipt of a live, attenuated vaccine within 4 weeks prior to randomisation or
anticipation that a live, attenuated vaccine will be required during
atezolizumab/placebo treatment or within 5 months after the last dose of
atezolizumab/placebo

- Prior treatment with CD137 agonists, anti-PD-1, or anti-PD-L1 therapeutic antibody or
pathway targeting agents

- Treatment with systemic immunostimulatory agents (including but not limited to
interferons or interleukin [IL]-2) within 4 weeks or five half-lives of the drug
(whichever is longer) prior to randomisation

- Treatment with systemic corticosteroids or other systemic immunosuppressive
medications within 2 weeks prior to start of study treatment, or anticipated
requirement for systemic immunosuppressive medications during the trial

Exclusion Criteria Related to Capecitabine:

- Inability to swallow pills

- Malabsorption syndrome, disease significantly affecting gastrointestinal function,
resection of the stomach or small bowel, or ulcerative colitis

- Known dihydropyrimidine dehydrogenase (DPD) deficiency or history of severe and
unexpected reactions to fluoropyrimidine therapy in patients selected to


Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Triple Negative Breast Neoplasms

Intervention(s)

Drug: Capecitabine

Drug: Placebo

Drug: Carboplatin

Drug: Gemcitabine

Drug: Atezolizumab

Primary Outcome(s)

Overall Survival (OS) in Population With Programmed Death-Ligand 1 (PD-L1)-Positive Tumour Status [Time Frame: Baseline to end of study (approximately 58 months)]

Overall Survival (OS) in Modified Intent-To-Treat (mITT) Popluation [Time Frame: Baseline to end of study (approximately 58 months)]

Secondary Outcome(s)

Duration of Objective Response (DoR) [Time Frame: Time from the first occurrence of a documented objective response to disease progression or death (through the end of study, approximately 58 months)]

Minimum Serum Concentration (Cmin) of Atezolizumab [Time Frame: At pre-defined intervals from Day 1, Cycle 1 through Cycle 4 (cycle = 21 days)]

Objective Response Rate (ORR) in Modified Intent-To-Treat (mITT) Popluation [Time Frame: Baseline; every 8 weeks for the first 12 months after randomisation, and every 12 weeks thereafter until disease progression, withdrawal of consent, death, or study termination (approximately 58 months)]

Objective Response Rate (ORR) in Population With Programmed Death-Ligand 1 (PD-L1)-Positive Tumour Status [Time Frame: Baseline; every 8 weeks for the first 12 months after randomisation, and every 12 weeks thereafter until disease progression, withdrawal of consent, death, or study termination (approximately 58 months)]

Progression Free Survival (PFS) in China Population With Programmed Death-Ligand 1 (PD-L1)-Positive Tumour Status [Time Frame: Randomisation to the first occurrence of disease progression or death (through the end of study, approximately 58 months)]

Progression-Free Survival (PFS) in Population With Programmed Death-Ligand 1 (PD-L1)-Positive Tumour Status [Time Frame: Randomisation to the first occurrence of disease progression or death (through the end of study, approximately 58 months)]

Clinical Benefit Rate (CBR) in China Population [Time Frame: 8 weeks for the first 12 months after treatment initiation and every 12 weeks thereafter until disease progression (through the end of study, approximately 58 months)]

Incidence of Anti-Drug Antibodies (ADAs) to Atezolizumab [Time Frame: Baseline to end of study (approximately 58 months)]

Duration of Objective Response (DoR) in China Population [Time Frame: Time from the first occurrence of a documented objective response to disease progression or death (through the end of study, approximately 58 months)]

Duration of Response for Confirmed Responders (C-DoR) in China Population [Time Frame: Time from the first occurrence of a documented objective response to disease progression or death (through the end of study, approximately 58 months)]

Confirmed Objective Response Rate (C-ORR) [Time Frame: Baseline; every 8 weeks for the first 12 months after randomisation, and every 12 weeks thereafter until disease progression, withdrawal of consent, death, or study termination (approximately 58 months)]

Percentage of Participants With Adverse Events [Time Frame: Baseline to end of study (approximately 58 months)]

Proportion of Participants Alive 18 Months [Time Frame: Randomization to 18 months post randomization]

Confirmed Objective Response Rate (C-ORR) in China Population [Time Frame: Baseline; every 8 weeks for the first 12 months after randomisation, and every 12 weeks thereafter until disease progression, withdrawal of consent, death, or study termination (approximately 58 months)]

Duration of Response for Confirmed Responders (C-DoR) [Time Frame: Time from the first occurrence of a documented objective response to disease progression or death (through the end of study, approximately 58 months)]

ORR in Modified Intent-To-Treat (mITT) China Popluation [Time Frame: Baseline; every 8 weeks for the first 12 months after randomisation, and every 12 weeks thereafter until disease progression, withdrawal of consent, death, or study termination (approximately 58 months)]

Proportion of Participants Alive 18 Months in China Population [Time Frame: Randomization to 18 months post randomization]

Maximum Serum Concentration (Cmax) of Atezolizumab [Time Frame: At pre-defined intervals from Day 1, Cycle 1 through Cycle 4 (cycle = 21 days)]

Overall Survival (OS) in China Population With Programmed Death-Ligand 1 (PD-L1)-Positive Tumour Status [Time Frame: Baseline to end of study (approximately 58 months)]

Time to Confirmed Deterioration (TTD) of GHS/QoL in China Population [Time Frame: Baseline to end of study (approximately 58 months)]

Progression Free Survival (PFS) in mITT China Population [Time Frame: Randomisation to the first occurrence of disease progression or death (through the end of study, approximately 58 months)]

Overall Survival (OS) in mITT China Popluation [Time Frame: Baseline to end of study (approximately 58 months)]

Progression-Free Survival (PFS) in mITT population [Time Frame: Randomisation to the first occurrence of disease progression or death (through the end of study, approximately 58 months)]

Relationship Between PD-L1 Protein Expression in Screening Tumour Tissue and Clinical Outcomes [Time Frame: Baseline to end of study (approximately 58 months)]

Clinical Benefit Rate (CBR) [Time Frame: 8 weeks for the first 12 months after treatment initiation and every 12 weeks thereafter until disease progression (through the end of study, approximately 58 months)]

Objective Response Rate (ORR) in China Population With Programmed Death-Ligand 1 (PD-L1)-Positive Tumour Status [Time Frame: Baseline; every 8 weeks for the first 12 months after randomisation, and every 12 weeks thereafter until disease progression, withdrawal of consent, death, or study termination (approximately 58 months)]

Proportion of Participants Alive 12 Months [Time Frame: Randomization to 12 months post randomization]

Proportion of Participants Alive 12 Months in China Population [Time Frame: Randomization to 12 months post randomization]

Time to Confirmed Deterioration (TTD) of GHS/QoL [Time Frame: Baseline to end of study (approximately 58 months)]

Secondary ID(s)

2016-005119-42

MO39193

Source(s) of Monetary Support

Please refer to primary and secondary sponsors