A Study of Atezolizumab and Paclitaxel Versus Placebo and Paclitaxel in Participants With Previously Untreated Locally Advanced or Metastatic Triple Negative Breast Cancer (TNBC)

• Register: ClinicalTrials.gov
• Last refreshed on: 22 January 2024
• Main ID: NCT03125902
• Date of registration: 20/04/2017
• Prospective Registration: Yes
• Primary sponsor: Hoffmann-La Roche
• Public title: A Study of Atezolizumab and Paclitaxel Versus Placebo and Paclitaxel in Participants With Previously Untreated Locally Advanced or Metastatic Triple Negative Breast Cancer (TNBC) IMpassion131
• Scientific title: A Phase III, Multicenter, Randomised, Double-Blind, Placebo-Controlled Study of Atezolizumab (Anti-Pd-L1 Antibody) in Combination With Paclitaxel Compared With Placebo With Paclitaxel for Patients With Previously Untreated Inoperable Locally Advanced or Metastatic Triple Negative Breast Cancer
• Date of first enrolment: August 25, 2017
• Target sample size: 653
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/ct2/show/NCT03125902
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Double (Participant, Investigator).
• Phase: Phase 3

Countries of recruitment

Algeria, Argentina, Brazil, Canada, China, Croatia, Czechia, Egypt, France, Germany, Greece, India, Israel, Italy, Japan, Korea, Republic of, Lebanon, Morocco, Romania, Russian Federation, Saudi Arabia, Slovakia, South Africa, Spain, Turkey, United Kingdom, United States, Vietnam

Contacts

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

Key inclusion & exclusion criteria

Inclusion Criteria:

- Participants with locally advanced or metastatic, histologically documented TNBC
(absence of human epidermal growth factor receptor 2 [HER2], estrogen receptor [ER],
and progesterone receptor [PR] expression), not amenable to surgical therapy

- Participants eligible for taxane monotherapy

- No prior chemotherapy or targeted systemic therapy (including endocrine therapy) for
inoperable locally advanced or metastatic TNBC

- Availability of formalin-fixed paraffin-embedded (FFPE) tumor block (preferred) or at
least 17 unstained slides, collected =3 months prior to randomization, with an
associated pathology report, if available. If a tumour sample taken within 3 months
before randomisation is not available and a tumour biopsy is not clinically feasible,
the primary surgical resection sample or the most recent FFPE tumour biopsy sample may
be used. Of these additional options, the most recent sample should be used.

- Eastern Cooperative Oncology Group performance status of 0 or 1

- Life expectancy at least 12 weeks

- Measurable disease, as defined by RECIST v1.1

- Adequate hematologic and end-organ function

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

- 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 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. The HCV RNA test will be
performed only for patients who have a positive HCV antibody test.

- Women of child bearing potential must have a negative serum pregnancy test result
within 7 days prior to initiation of study drug

- For men and women of child bearing potential: agreement to remain abstinent or use
protocol defined contraceptive measures during the treatment period and for at least 5
months after the last dose of atezolizumab/placebo, or for at least 6 months after the
last dose of paclitaxel

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 at least 2 weeks prior to randomization

- Known central nervous system (CNS) disease, except for treated asymptomatic CNS
metastases

- Leptomeningeal disease

- Uncontrolled pleural effusion, pericardial effusion, or ascites

- Uncontrolled tumor-related pain, or uncontrolled hypercalcemia or clinically
significant (symptomatic) hypercalcemia

- Malignancies other than TNBC within 5 years prior to randomization, with the exception
of those with a negligible risk of metastasis or death and treated with expected
curative outcome (such as adequately treated carcinoma in situ of the cervix,
non-melanoma skin carcinoma, or Stage I uterine cancer)

- Pregnant or breast-feeding women, or intending to become pregnant during the study

- Evidence of significant uncontrolled concomitant disease that could affect compliance
with the protocol or interpretation of results, including significant liver disease,
cardiovascular disease, and presence of an abnormal electrocardiogram (ECG)

- Serious infection requiring antibiotics within 2 weeks prior to randomization,
including but not limited to infections requiring hospitalization or IV antibiotics,
such as bacteremia, or severe pneumonia

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

- Treatment with investigational therapy within 30 days prior to initiation of study
treatment

- History of hypersensitivity reactions to study drug or any component of the study drug
formulation



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

Health Condition(s) or Problem(s) studied

Triple-Negative Breast Cancer

Intervention(s)

Drug: Atezolizumab Placebo

Drug: Paclitaxel

Drug: Atezolizumab (MPDL3280A), an engineered anti-PDL1 antibody

Primary Outcome(s)

Progression-Free Survival (PFS) Assessed Using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) in the Intent-to-Treat (ITT) Population [Time Frame: From Day 1 to disease progression (PD) or death from any cause, assessed up to primary completion date (approximately 26 months)]

Progression-Free Survival (PFS) Assessed Using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) in the Subpopulation With Programmed Death-Ligand 1 (PD-L1)-Positive Tumour Status [Time Frame: From Day 1 to disease progression (PD) or death from any cause, assessed up to primary completion date (approximately 26 months)]

Secondary Outcome(s)

Minimum Observed Serum Concentration (Cmin) of Atezolizumab in PK Evaluable Population [Time Frame: Pre-dose (0 hours) on Day 1 of Cycles 2-4 and at treatment discontinuation (TD), (approximately 9 months).]

Maximum Observed Plasma Concentration (Cmax) of Paclitaxel [Time Frame: Pre-dose (0 hours), 5-10 min before and after paclitaxel infusion, 60 min after paclitaxel infusion on Day 1 of Cycles 1 and 3 (paclitaxel infusion duration= 60 min) (1 Cycle = 28 days)]

Time to Deterioration (TTD) in Global Health Status/ Health Related Quality of Life (HRQoL) in the PRO Evaluable Population [Time Frame: From Day 1 to deterioration, assessed up to primary completion date (approximately 26 months)]

Maximum Observed Serum Concentration (Cmax) of Atezolizumab in PK-evaluable Population [Time Frame: C1D1 30 min postdose]

Overall Survival by PD-L1 Status, Intent to Treat Population [Time Frame: From Day 1 up to primary completion date (approximately 26 months)]

Overall Survival (OS) in the PD-L1-Positive Subpopulation [Time Frame: From Day 1 to death from any cause, assessed up to primary completion date (approximately 26 months)]

Percentage of Participants Who Are Alive at 12 and 18 Months [Time Frame: From Day 1 to death from any cause, assessed up to 12 and 18 months]

Percentage of Participants With Anti-Drug Antibodies' (ADAs) Against Atezolizumab in ADA Evaluable Population [Time Frame: Pre-dose (0 hours) on Day 1 of Cycles 1, 2, 3, 4, 8, 12, 16, and at every 8 cycles thereafter until TD, at TD, and at 90-150 days after TD (maximum up to 45 months) (1 Cycle = 28 days)]

Minimum Observed Plasma Concentration (Cmin) of Paclitaxel [Time Frame: Pre-dose (0 hours) on Day 1 of Cycle 3 (1 Cycle = 28 days)]

Percentage of Participants With Adverse Events (AEs) and Serious AEs (SAEs) [Time Frame: From Day 1 to 90 days after last dose of study drug, assessed up to primary completion date (approximately 26 months)]

Percentage of Participants With Clinical Benefit Assessed Using RECIST v1.1 in Response-evaluable Population [Time Frame: From Day 1 to PD, assessed up to primary completion date (approximately 26 months)]

Percentage of Participants With Objective Response Assessed Using RECIST v1.1 in the PD-L1-Positive Population (Confirmed, Investigator-Assessed ) [Time Frame: From Day 1 to PD, assessed up to primary completion date (approximately 26 months)]

Percentage of Participants With Objective Response Assessed Using RECIST v1.1 in the Response-Evaluable Population (Confirmed, Investigator-Assessed ) [Time Frame: From Day 1 to PD, assessed up to primary completion date (approximately 26 months)]

Percentage of Participants With Objective Response Assessed Using RECIST v1.1 in the Response-Evaluable Population (Unconfirmed, Investigator-Assessed ) [Time Frame: From Day 1 to PD, assessed up to primary completion date (approximately 26 months)]

Duration of Confirmed Response (C-DoR) in (C-DoR)-Evaluable Population [Time Frame: From objective response to PD, assessed up to primary completion date (approximately 26 months)]

Duration of Objective Response (DOR) Assessed Using RECIST v1.1 in DOR-evaluable Population (Unconfirmed) [Time Frame: From objective response to PD, assessed up to primary completion date (approximately 26 months)]

Percentage of Participants With Objective Response Assessed Using RECIST v1.1 in the PD-L1-Positive Population (Unconfirmed, Investigator-Assessed) [Time Frame: From Day 1 to PD, assessed up to primary completion date (approximately 26 months)]

Overall Survival (OS) in the ITT Population [Time Frame: From Day 1 to death from any cause, assessed up to primary completion date (approximately 26 months)]

Progression Free Survival by PD-L1 Status, Intent to Treat Population [Time Frame: From Day 1 up to primary completion date (approximately 26 months)]

Percentage of Participants Who Are Alive Without Progression Event at Month 12 Assessed Using RECIST v1.1 [Time Frame: From Day 1 to PD or death from any cause, assessed up to 12 months]

Secondary ID(s)

2016-004024-29

MO39196

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 07/01/2021
• URL: https://clinicaltrials.gov/ct2/show/results/NCT03125902