Brief Summary
This multicenter, randomized, double-blind study evaluated the efficacy, safety, and pharmacokinetics of atezolizumab (MPDL3280A) administered with nab-paclitaxel compared with placebo in combination with nab-paclitaxel in participants with locally advanced or metastatic triple-negative breast cancer (TNBC) who have not received prior systemic therapy for metastatic breast cancer (mBC). The safety of single-agent nab-paclitaxel has been determined in previous studies of participants with mBC and the safety data to date suggest that atezolizumab can be safely combined with standard chemotherapy agents.
Brief Title
A Study of Atezolizumab in Combination With Nab-Paclitaxel Compared With Placebo With Nab-Paclitaxel for Participants With Previously Untreated Metastatic Triple-Negative Breast Cancer (IMpassion130)
Categories
Completion Date
Completion Date Type
Actual
Conditions
Triple Negative Breast Cancer
Eligibility Criteria
Inclusion Criteria:
* Metastatic or locally advanced, histologically documented TNBC characterized by absence of human epidermal growth factor 2 (HER2), estrogen receptor (ER), and progesterone receptor (PR) expression
* No prior chemotherapy or targeted systemic therapy for inoperable locally advanced or metastatic TNBC
* Eligible for taxane monotherapy (i.e., absence of rapid clinical progression, life-threatening visceral metastases, or the need for rapid symptom and/or disease control)
* A representative formalin-fixed, paraffin-embedded tumor specimen in paraffin blocks, or at least 20 unstained slides with an associated pathology report documenting ER, PR, and HER2 negativity. Participants with fewer than 20 unstained slides available at baseline, and not fewer than 12 unstained slides will be eligible upon discussion with Medical Monitor
* Eastern Cooperative Oncology Group performance status of 0 or 1
* Measurable disease as defined by RECIST v1.1
* Adequate hematologic and end-organ function
Exclusion Criteria:
* Known central nervous system (CNS) disease, except for treated asymptomatic CNS metastases
* Leptomeningeal disease
* Pregnancy or lactation
* History of autoimmune disease
* Prior allogeneic stem cell or solid organ transplantation
* Positive test for human immunodeficiency virus
* Active hepatitis B or hepatitis C
* Receipt of a live, attenuated vaccine within 4 weeks prior to randomization, during treatment, or within 5 months following the last dose of atezolizumab/placebo
* Metastatic or locally advanced, histologically documented TNBC characterized by absence of human epidermal growth factor 2 (HER2), estrogen receptor (ER), and progesterone receptor (PR) expression
* No prior chemotherapy or targeted systemic therapy for inoperable locally advanced or metastatic TNBC
* Eligible for taxane monotherapy (i.e., absence of rapid clinical progression, life-threatening visceral metastases, or the need for rapid symptom and/or disease control)
* A representative formalin-fixed, paraffin-embedded tumor specimen in paraffin blocks, or at least 20 unstained slides with an associated pathology report documenting ER, PR, and HER2 negativity. Participants with fewer than 20 unstained slides available at baseline, and not fewer than 12 unstained slides will be eligible upon discussion with Medical Monitor
* Eastern Cooperative Oncology Group performance status of 0 or 1
* Measurable disease as defined by RECIST v1.1
* Adequate hematologic and end-organ function
Exclusion Criteria:
* Known central nervous system (CNS) disease, except for treated asymptomatic CNS metastases
* Leptomeningeal disease
* Pregnancy or lactation
* History of autoimmune disease
* Prior allogeneic stem cell or solid organ transplantation
* Positive test for human immunodeficiency virus
* Active hepatitis B or hepatitis C
* Receipt of a live, attenuated vaccine within 4 weeks prior to randomization, during treatment, or within 5 months following the last dose of atezolizumab/placebo
Inclusion Criteria
Inclusion Criteria:
* Metastatic or locally advanced, histologically documented TNBC characterized by absence of human epidermal growth factor 2 (HER2), estrogen receptor (ER), and progesterone receptor (PR) expression
* No prior chemotherapy or targeted systemic therapy for inoperable locally advanced or metastatic TNBC
* Eligible for taxane monotherapy (i.e., absence of rapid clinical progression, life-threatening visceral metastases, or the need for rapid symptom and/or disease control)
* A representative formalin-fixed, paraffin-embedded tumor specimen in paraffin blocks, or at least 20 unstained slides with an associated pathology report documenting ER, PR, and HER2 negativity. Participants with fewer than 20 unstained slides available at baseline, and not fewer than 12 unstained slides will be eligible upon discussion with Medical Monitor
* Eastern Cooperative Oncology Group performance status of 0 or 1
* Measurable disease as defined by RECIST v1.1
* Adequate hematologic and end-organ function
* Metastatic or locally advanced, histologically documented TNBC characterized by absence of human epidermal growth factor 2 (HER2), estrogen receptor (ER), and progesterone receptor (PR) expression
* No prior chemotherapy or targeted systemic therapy for inoperable locally advanced or metastatic TNBC
* Eligible for taxane monotherapy (i.e., absence of rapid clinical progression, life-threatening visceral metastases, or the need for rapid symptom and/or disease control)
* A representative formalin-fixed, paraffin-embedded tumor specimen in paraffin blocks, or at least 20 unstained slides with an associated pathology report documenting ER, PR, and HER2 negativity. Participants with fewer than 20 unstained slides available at baseline, and not fewer than 12 unstained slides will be eligible upon discussion with Medical Monitor
* Eastern Cooperative Oncology Group performance status of 0 or 1
* Measurable disease as defined by RECIST v1.1
* Adequate hematologic and end-organ function
Gender
All
Gender Based
false
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT02425891
Org Class
Industry
Org Full Name
Hoffmann-La Roche
Org Study Id
WO29522
Overall Status
Completed
Phases
Phase 3
Primary Completion Date
Primary Completion Date Type
Actual
Official Title
A Phase III, Multicenter, Randomized, Placebo-Controlled Study of Atezolizumab (Anti-PD-L1 Antibody) in Combination With Nab-Paclitaxel Compared With Placebo With Nab-Paclitaxel for Patients With Previously Untreated Metastatic Triple-Negative Breast Cancer
Primary Outcomes
Outcome Description
PFS was defined as the time from randomization to the occurrence of disease progression, as determined by investigators from tumor assessments per RECIST v1.1, or death from any cause, whichever occurred first.
Outcome Measure
Progression Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 (v1.1) in All Randomized Participants
Outcome Time Frame
Baseline up to approximately 34 months
Outcome Description
PFS was defined as the time from randomization to the occurrence of disease progression, as determined by investigators from tumor assessments per RECIST v1.1, or death from any cause, whichever occurred first.
Outcome Measure
PFS According to RECIST v1.1 in Participants With Detectable Programmed Death-Ligand 1 (PD-L1)
Outcome Time Frame
Baseline up to approximately 34 months
Outcome Description
OS was defined as the time from the date of randomization to the date of death from any cause.
Outcome Measure
Overall Survival (OS) in All Randomized Participants
Outcome Time Frame
Baseline until death due to any cause (up to approximately 58 months)
Outcome Description
OS was defined as the time from the date of randomization to the date of death from any cause.
Outcome Measure
OS in Participants With Detectable PD-L1
Outcome Time Frame
Baseline until death due to any cause (up to approximately 58 months)
Secondary Ids
Secondary Id
2014-005490-37
Secondary Outcomes
Outcome Description
An objective response was defined for participants with measurable disease at baseline as either a partial response (PR) or a complete response (CR) using RECIST v1.1.
Outcome Time Frame
Baseline up to approximately 34 months
Outcome Measure
Percentage of Participants With an Objective Response of Complete Response (CR) or Partial Response (PR) According to RECIST v1.1 in All Randomized Participants
Outcome Description
An objective response was defined for participants with measurable disease at baseline as either a partial response (PR) or a complete response (CR) using RECIST v1.1.
Outcome Time Frame
Baseline up to approximately 34 months
Outcome Measure
Percentage of Participants With an Objective Response of CR or PR According to RECIST v1.1 in Participants With Detectable PD-L1
Outcome Description
DOR was defined for participants who had an objective response as the time from the first occurrence of a documented unconfirmed response (CR or PR) to the date of disease progression per RECIST v1.1 or death from any cause, whichever occurred first.
Outcome Time Frame
Baseline up to approximately 34 months
Outcome Measure
Duration of Response (DOR) According to RECIST v1.1 in All Randomized Participants
Outcome Description
DOR was defined for participants who had an objective response as the time from the first occurrence of a documented unconfirmed response (CR or PR) to the date of disease progression per RECIST v1.1 or death from any cause, whichever occurred first.
Outcome Time Frame
Baseline up to approximately 34 months
Outcome Measure
DOR Acccording to RECIST v1.1 in Participants With Detectable PD-L1
Outcome Description
Deterioration in GHS/HRQoL (Items 29, 30 of the EORTC QLQ C30) was defined by the following two criteria: 1. The time from randomization to the first time the participant's GHS/HRQoL scale score showed a \>=10-point decrease from the baseline scale score. A 10-point change was defined as the minimally important difference (MID). 2. The score decrease of \>= 10-points from baseline was held for at least two consecutive cycles, or an initial score decrease of \>= 10-points was followed by death or treatment discontinuation within 3 weeks from the last assessment.
Outcome Time Frame
Baseline up to approximately 58 months
Outcome Measure
Time to Deterioration (TTD) in Global Health Status/Health Related Quality of Life According to European Organisation for Research and Treatment of Cancer (EORTC) Quality-of-Life Questionnaire Core 30 (QLQ-C30) v3.0 in All Randomized Participants
Outcome Description
Deterioration in GHS/HRQoL (Items 29, 30 of the EORTC QLQ C30) was defined by the following two criteria: 1. The time from randomization to the first time the participants's GHS/HRQoL scale score showed a \>=10-point decrease from the baseline scale score. A 10-point change was defined as the minimally important difference (MID). 2. The score decrease of \>= 10-points from baseline was held for at least two consecutive cycles, or an initial score decrease of \>= 10-points was followed by death or treatment discontinuation within 3 weeks from the last assessment.
Outcome Time Frame
Baseline up to approximately 58 months
Outcome Measure
TTD in Global Health Status/Health Related Quality of Life According to EORTC QLQ-C30 v3.0 in Participants With Detectable PD-L1
Outcome Description
Percentage of participants with at least one adverse event.
Outcome Time Frame
Baseline up to to the data cutoff date: 31 August 2021 (up to approximately 74 months)
Outcome Measure
Percentage of Participants With at Least One Adverse Event
Outcome Description
Percentage of Participants with Anti-Therapeutic Antibodies (ATAs) Against Atezolizumab
Outcome Time Frame
Baseline up to approximately 53 months
Outcome Measure
Percentage of Participants With Anti-Therapeutic Antibodies (ATAs) Against Atezolizumab
Outcome Description
Maximum serum concentration for atezolizumab.
Outcome Time Frame
Cycle 1 Day 1 (Cycle = 28 days)
Outcome Measure
Maximum Serum Concentration (Cmax) for Atezolizumab
Outcome Description
Minimum serum concentration for atezolizumab.
Outcome Time Frame
Day 27 of Cycle 1, 2, 3, and 7 (Cycle = 28 days)
Outcome Measure
Minimum Serum Concentration (Cmin) for Atezolizumab
Outcome Description
Plasma Concentrations of Total Paclitaxel
Outcome Time Frame
Pre-dose (Hour 0) on Cycle 1 Day 1, pre-dose (Hour 0), 5-10 minutes before end of nab-paclitaxel infusion, 1 hour after end of nab-paclitaxel infusion (infusion duration = 30 minutes) on Cycle 3 Day 1 (Cycle = 28 days)
Outcome Measure
Plasma Concentrations of Total Paclitaxel
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Estimated
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Joseph Sparano
Investigator Email
jsparano@montefiore.org
Investigator Phone
718-405-8404