NCT03125902 · CITED IN SOURCE DOCUMENTS

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

An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.

Phase: PHASE3
Status at capture: COMPLETED
Registry last update: 2024-03-26

This Phase 3, multicenter, randomized, double-blind, placebo controlled study is designed to evaluate the efficacy and safety of atezolizumab (MPDL3280A, an anti-programmed death-ligand 1 \[PD-L1\] antibody) administered in combination with paclitaxel compared with placebo in combination with paclitaxel in participants with previously untreated, inoperable locally advanced or metastatic, centrally confirmed TNBC. Participants will be randomized in a 2:1 ratio to receive atezolizumab or placebo plus paclitaxel until disease progression or unacceptable toxicity or end of study, whichever occurs first (maximum up to approximately 40 months). In addition, the Sponsor may decide to terminate the study at any time.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

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

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outcome · POSTED

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

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outcome · POSTED

Overall Survival (OS) in the PD-L1-Positive Subpopulation

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outcome · POSTED

Overall Survival (OS) in the ITT Population

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outcome · POSTED

Percentage of Participants Who Are Alive at 12 and 18 Months

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outcome · POSTED

Time to Deterioration (TTD) in Global Health Status/ Health Related Quality of Life (HRQoL) in the PRO Evaluable Population

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outcome · POSTED

Percentage of Participants Who Are Alive Without Progression Event at Month 12 Assessed Using RECIST v1.1

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outcome · POSTED

Percentage of Participants With Objective Response Assessed Using RECIST v1.1 in the PD-L1-Positive Population (Confirmed, Investigator-Assessed )

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outcome · POSTED

Percentage of Participants With Objective Response Assessed Using RECIST v1.1 in the PD-L1-Positive Population (Unconfirmed, Investigator-Assessed)

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outcome · POSTED

Percentage of Participants With Objective Response Assessed Using RECIST v1.1 in the Response-Evaluable Population (Confirmed, Investigator-Assessed )

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outcome · POSTED

Percentage of Participants With Objective Response Assessed Using RECIST v1.1 in the Response-Evaluable Population (Unconfirmed, Investigator-Assessed )

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outcome · POSTED

Duration of Objective Response (DOR) Assessed Using RECIST v1.1 in DOR-evaluable Population (Unconfirmed)

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outcome · POSTED

Percentage of Participants With Clinical Benefit Assessed Using RECIST v1.1 in Response-evaluable Population

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outcome · POSTED

Minimum Observed Serum Concentration (Cmin) of Atezolizumab in PK Evaluable Population

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outcome · POSTED

Maximum Observed Serum Concentration (Cmax) of Atezolizumab in PK-evaluable Population

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outcome · POSTED

Minimum Observed Plasma Concentration (Cmin) of Paclitaxel

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outcome · POSTED

Maximum Observed Plasma Concentration (Cmax) of Paclitaxel

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outcome · POSTED

Percentage of Participants With Adverse Events (AEs) and Serious AEs (SAEs)

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outcome · POSTED

Percentage of Participants With Anti-Drug Antibodies' (ADAs) Against Atezolizumab in ADA Evaluable Population

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outcome · POSTED

Overall Survival by PD-L1 Status, Intent to Treat Population

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outcome · POSTED

Progression Free Survival by PD-L1 Status, Intent to Treat Population

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outcome · POSTED

Duration of Confirmed Response (C-DoR) in (C-DoR)-Evaluable Population

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part

eligibility 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
healthy Volunteers: false
minimum Age: 18 Years
sex: ALL
std Ages: ADULT
OLDER_ADULT

Treatment arms and interventions

arm Groups

description
Participants will receive placebo matching to atezolizumab via IV infusion on Days 1 and 15 (± 3 days) of every 28-day cycle along with paclitaxel administered at a dose of 90 mg/m\^2 via IV infusion on Days 1, 8, and 15 of every 28-day cycle until disease progression or unacceptable toxicity.
intervention Names
Drug: Atezolizumab (MPDL3280A), an engineered anti-PDL1 antibody
Drug: Paclitaxel
label
Placebo and Paclitaxel
type
PLACEBO_COMPARATOR
description
Participants will receive atezolizumab at a dose of 840 milligrams (mg) via intravenous (IV) infusion on Days 1 and 15 (± 3 days) of every 28-day cycle along with paclitaxel administered at a dose of 90 mg per square meter (mg/m\^2) via IV infusion on Days 1, 8, and 15 of every 28-day cycle until disease progression or unacceptable toxicity.
intervention Names
Drug: Atezolizumab Placebo
Drug: Paclitaxel
label
Atezolizumab and Paclitaxel
type
EXPERIMENTAL

interventions

arm Group Labels
Placebo and Paclitaxel
description
Atezolizumab will be administered at a dose of 840 mg via IV infusion on Days 1 and 15 (± 3 days) of every 28-day cycle.
name
Atezolizumab (MPDL3280A), an engineered anti-PDL1 antibody
other Names
MPDL3280A, TECENTRIQ
type
DRUG
arm Group Labels
Atezolizumab and Paclitaxel
description
Placebo matching to atezolizumab will be administered via IV infusion on Days 1 and 15 (± 3 days) of every 28-day cycle.
name
Atezolizumab Placebo
type
DRUG
arm Group Labels
Atezolizumab and Paclitaxel
Placebo and Paclitaxel
description
Paclitaxel will be administered at a dose of 90 mg/m\^2 via IV infusion on Days 1, 8, and 15 of every 28-day cycle.
name
Paclitaxel
type
DRUG

Study design

allocation

RANDOMIZED

intervention Model

PARALLEL

masking Info

masking: DOUBLE
masking Description: The Sponsor and its agents; the study site personnel, including the investigator; and the participant will be blinded to treatment assignment.
who Masked: PARTICIPANT
INVESTIGATOR

primary Purpose

TREATMENT

Enrollment

count: 653
type: ACTUAL

Registered outcome plans (not posted results)

primary Outcomes

description
PFS is defined as the time from randomization to the first occurrence of PD, as determined by the investigator using RECIST v1.1, or death from any cause during the study, whichever occurs first. PD is defined as greater than or equal to (\>/=) 20 percent (%) relative increase and \>/=5 millimeter (mm) of absolute increase in the sum of diameters (SD) of target lesions (TLs), taking as reference the smallest SD recorded since treatment started, or appearance of 1 or more new lesions.
measure
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)
description
PFS is defined as the time from randomization to the first occurrence of PD, as determined by the investigator using RECIST v1.1, or death from any cause during the study, whichever occurs first. PD is defined as greater than or equal to (\>/=) 20 percent (%) relative increase and \>/=5 millimeter (mm) of absolute increase in the sum of diameters (SD) of target lesions (TLs), taking as reference the smallest SD recorded since treatment started, or appearance of 1 or more new lesions.
measure
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)

secondary Outcomes

description
OS is defined as the time from randomization to death from any cause. Results from a pre-specified interim analysis.
measure
Overall Survival (OS) in the PD-L1-Positive Subpopulation
time Frame
From Day 1 to death from any cause, assessed up 36 months
description
OS is defined as the time from randomization to death from any cause. Results from a pre-specified interim analysis.
measure
Overall Survival (OS) in the ITT Population
time Frame
From Day 1 to death from any cause, assessed up to end of study (up to approximately 36 months)
measure
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
description
Deterioration in Global Health Status/HRQoL is defined as a decrease of at least 10 points on the Global Health Status /HRQoL scale (comprised of 2 items: 29 and 30) of the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30). The 2 items use 7-point scale (1 = very poor to 7 = Excellent). Scores are averaged, transformed to 0-100 scale; where higher score=better level of functioning or greater degree of symptoms.
measure
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 64 months
description
PD is defined as \>/=20% relative increase and \>/=5 mm of absolute increase in the SD of TLs, taking as reference the smallest SD recorded since treatment started, or appearance of 1 or more new lesions.
measure
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
description
Objective response is defined as complete response (CR) or partial response (PR), as determined by the investigator using RECIST v1.1 criteria. CR is defined as the disappearance of all TLs and SA reduction to less than (\<) 10mm for nodal TLs/ non-TLs. PR is defined as \>/=30% decrease in SD of TLs, taking as reference the baseline SD. Responses were confirmed after 8 weeks if within first 12 months or after 12 weeks if later.
measure
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)
description
Objective response is defined as complete response (CR) or partial response (PR), as determined by the investigator using RECIST v1.1 criteria. CR is defined as the disappearance of all TLs and SA reduction to less than (\<) 10mm for nodal TLs/ non-TLs. PR is defined as \>/=30% decrease in SD of TLs, taking as reference the baseline SD.
measure
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)
description
Objective response is defined as complete response (CR) or partial response (PR), as determined by the investigator using RECIST v1.1 criteria. CR is defined as the disappearance of all TLs and SA reduction to less than (\<) 10mm for nodal TLs/ non-TLs. PR is defined as \>/=30% decrease in SD of TLs, taking as reference the baseline SD. Responses were confirmed after 8 weeks if within first 12 months or after 12 weeks if later.
measure
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)
description
Objective response is defined as complete response (CR) or partial response (PR), as determined by the investigator using RECIST v1.1 criteria. CR is defined as the disappearance of all TLs and SA reduction to less than (\<) 10mm for nodal TLs/ non-TLs. PR is defined as \>/=30% decrease in SD of TLs, taking as reference the baseline SD.
measure
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)
description
DOR is defined as the time period from the date of initial CR or PR until the date of PD or death from any cause, whichever occurs first. CR is defined as the disappearance of all TLs and SA reduction to \<10mm for nodal TLs/ non-TLs. PR is defined as \>/=30% decrease in SD of TLs, taking as reference the baseline SD. PD is defined as \>/=20% relative increase and \>/=5 mm of absolute increase in the SD of TLs, taking as reference the smallest SD recorded since treatment started, or appearance of 1 or more new lesions.
measure
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)
description
Clinical benefit is defined as the achievement of CR, PR, or stable disease according to RECIST v1.1 that lasts for at least 6 months. CR is defined as the disappearance of all TLs and SA reduction to \<10mm for nodal TLs/ non-TLs. PR is defined as \>/=30% decrease in SD of TLs, taking as reference the baseline SD. PD is defined as \>/=20% relative increase and \>/=5 mm of absolute increase in the SD of TLs, taking as reference the smallest SD recorded since treatment started, or appearance of 1 or more new lesions. Stable disease is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD taking as reference smallest SD since treatment started.
measure
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)
measure
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).

Full study description

brief Summary: This Phase 3, multicenter, randomized, double-blind, placebo controlled study is designed to evaluate the efficacy and safety of atezolizumab (MPDL3280A, an anti-programmed death-ligand 1 \[PD-L1\] antibody) administered in combination with paclitaxel compared with placebo in combination with paclitaxel in participants with previously untreated, inoperable locally advanced or metastatic, centrally confirmed TNBC. Participants will be randomized in a 2:1 ratio to receive atezolizumab or placebo plus paclitaxel until disease progression or unacceptable toxicity or end of study, whichever occurs first (maximum up to approximately 40 months). In addition, the Sponsor may decide to terminate the study at any time.

Source references

references

citation
Miles D, Gligorov J, Andre F, Cameron D, Schneeweiss A, Barrios C, Xu B, Wardley A, Kaen D, Andrade L, Semiglazov V, Reinisch M, Patel S, Patre M, Morales L, Patel SL, Kaul M, Barata T, O'Shaughnessy J; IMpassion131 investigators. Primary results from IMpassion131, a double-blind, placebo-controlled, randomised phase III trial of first-line paclitaxel with or without atezolizumab for unresectable locally advanced/metastatic triple-negative breast cancer. Ann Oncol. 2021 Aug;32(8):994-1004. doi: 10.1016/j.annonc.2021.05.801. Epub 2021 Jul 1.
pmid
34219000
type
DERIVED