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)

Phase 3

Completed

Conditions: Triple Negative Breast Cancer

Interventions: Drug: Atezolizumab (MPDL3280A), an engineered anti-PDL1 antibody
Drug: Nab-Paclitaxel
Drug: Placebo

Registration Number: NCT02425891

Lead Sponsor: Hoffmann-La Roche

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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 902

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Atezolizumab Plus Nab-Paclitaxel	Atezolizumab (MPDL3280A), an engineered anti-PDL1 antibody	Participants assigned to atezolizumab plus nab-paclitaxel received both agents until disease progression or unacceptable toxicity.
Atezolizumab Plus Nab-Paclitaxel	Nab-Paclitaxel	Participants assigned to atezolizumab plus nab-paclitaxel received both agents until disease progression or unacceptable toxicity.
Placebo Plus Nab-Paclitaxel	Placebo	Participants assigned to placebo plus nab-paclitaxel received both agents until disease progression or unacceptable toxicity.
Placebo Plus Nab-Paclitaxel	Nab-Paclitaxel	Participants assigned to placebo plus nab-paclitaxel received both agents until disease progression or unacceptable toxicity.

Primary Outcome Measures

Name	Time	Method
Progression Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 (v1.1) in All Randomized Participants	Baseline up to approximately 34 months	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.
OS in Participants With Detectable PD-L1	Baseline until death due to any cause (up to approximately 58 months)	OS was defined as the time from the date of randomization to the date of death from any cause.
Overall Survival (OS) in All Randomized Participants	Baseline until death due to any cause (up to approximately 58 months)	OS was defined as the time from the date of randomization to the date of death from any cause.
PFS According to RECIST v1.1 in Participants With Detectable Programmed Death-Ligand 1 (PD-L1)	Baseline up to approximately 34 months	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.

Secondary Outcome Measures

Name	Time	Method
Percentage of Participants With an Objective Response of Complete Response (CR) or Partial Response (PR) According to RECIST v1.1 in All Randomized Participants	Baseline up to approximately 34 months	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.
Percentage of Participants With an Objective Response of CR or PR According to RECIST v1.1 in Participants With Detectable PD-L1	Baseline up to approximately 34 months	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.
Duration of Response (DOR) According to RECIST v1.1 in All Randomized Participants	Baseline up to approximately 34 months	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.
DOR Acccording to RECIST v1.1 in Participants With Detectable PD-L1	Baseline up to approximately 34 months	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.
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	Baseline up to approximately 58 months	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.
TTD in Global Health Status/Health Related Quality of Life According to EORTC QLQ-C30 v3.0 in Participants With Detectable PD-L1	Baseline up to approximately 58 months	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.
Percentage of Participants With at Least One Adverse Event	Baseline up to to the data cutoff date: 31 August 2021 (up to approximately 74 months)	Percentage of participants with at least one adverse event.
Percentage of Participants With Anti-Therapeutic Antibodies (ATAs) Against Atezolizumab	Baseline up to approximately 53 months	Percentage of Participants with Anti-Therapeutic Antibodies (ATAs) Against Atezolizumab
Maximum Serum Concentration (Cmax) for Atezolizumab	Cycle 1 Day 1 (Cycle = 28 days)	Maximum serum concentration for atezolizumab.
Minimum Serum Concentration (Cmin) for Atezolizumab	Day 27 of Cycle 1, 2, 3, and 7 (Cycle = 28 days)	Minimum serum concentration for atezolizumab.
Plasma Concentrations of Total Paclitaxel	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)	Plasma Concentrations of Total Paclitaxel

Trial Locations

Locations (247): University of Alabama at Birmingham
🇺🇸
Birmingham, Alabama, United States
Highlands Oncology Group
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Springdale, Arkansas, United States
Kaiser Permanente of Northern California
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Oakland, California, United States
Emad Ibrahim, Md, Inc
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Redlands, California, United States
Univ of Calif, San Francisco; Breast Cancer Center
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San Francisco, California, United States
Kaiser Permanente - San Marcos
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San Marcos, California, United States
Cancer Research Collaboration, Inc.
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Santa Ana, California, United States
Stanford Univ School of Med; Oncology
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Stanford, California, United States
Kaiser Permanente Of Colorado
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Aurora, Colorado, United States
Yale Cancer Center; Medical Oncology
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New Haven, Connecticut, United States
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University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States