Description:
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.
Title
- 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)
- 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
Clinical Trial IDs
- ORG STUDY ID:
WO29522
- SECONDARY ID:
2014-005490-37
- NCT ID:
NCT02425891
Conditions
- Triple Negative Breast Cancer
Interventions
Drug | Synonyms | Arms |
---|
Atezolizumab (MPDL3280A), an engineered anti-PDL1 antibody | Tecentriq, MPDL3280A | Atezolizumab Plus Nab-Paclitaxel |
Nab-Paclitaxel | Abraxane® | Atezolizumab Plus Nab-Paclitaxel |
Placebo | | Placebo Plus Nab-Paclitaxel |
Purpose
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.
Trial Arms
Name | Type | Description | Interventions |
---|
Atezolizumab Plus Nab-Paclitaxel | Experimental | Participants assigned to atezolizumab plus nab-paclitaxel received both agents until disease progression or unacceptable toxicity. | - Atezolizumab (MPDL3280A), an engineered anti-PDL1 antibody
- Nab-Paclitaxel
|
Placebo Plus Nab-Paclitaxel | Placebo Comparator | Participants assigned to placebo plus nab-paclitaxel received both agents until disease progression or unacceptable toxicity. | |
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
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Progression Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 (v1.1) in All Randomized Participants |
Time Frame: | Baseline up to approximately 34 months |
Safety Issue: | |
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. |
Secondary Outcome Measures
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 |
Time Frame: | Baseline up to approximately 34 months |
Safety Issue: | |
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. |
Measure: | Percentage of Participants With an Objective Response of CR or PR According to RECIST v1.1 in Participants With Detectable PD-L1 |
Time Frame: | Baseline up to approximately 34 months |
Safety Issue: | |
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. |
Measure: | Duration of Response (DOR) According to RECIST v1.1 in All Randomized Participants |
Time Frame: | Baseline up to approximately 34 months |
Safety Issue: | |
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. |
Measure: | DOR Acccording to RECIST v1.1 in Participants With Detectable PD-L1 |
Time Frame: | Baseline up to approximately 34 months |
Safety Issue: | |
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. |
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 |
Time Frame: | Baseline up to approximately 58 months |
Safety Issue: | |
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. |
Measure: | TTD in Global Health Status/Health Related Quality of Life According to EORTC QLQ-C30 v3.0 in Participants With Detectable PD-L1 |
Time Frame: | Baseline up to approximately 58 months |
Safety Issue: | |
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. |
Measure: | Percentage of Participants With Adverse Events (AEs) or Serious AEs (SAEs) |
Time Frame: | Baseline up to 53 months |
Safety Issue: | |
Description: | |
Measure: | Percentage of Participants With Anti-Therapeutic Antibodies (ATAs) Against Atezolizumab |
Time Frame: | Baseline up to approximately 53 months |
Safety Issue: | |
Description: | Percentage of Participants with Anti-Therapeutic Antibodies (ATAs) Against Atezolizumab |
Measure: | Maximum Serum Concentration (Cmax) for Atezolizumab |
Time Frame: | Cycle 1 Day 1 (Cycle = 28 days) |
Safety Issue: | |
Description: | Maximum serum concentration for atezolizumab. |
Measure: | Minimum Serum Concentration (Cmin) for Atezolizumab |
Time Frame: | Day 27 of Cycle 1, 2, 3, and 7 (Cycle = 28 days) |
Safety Issue: | |
Description: | Minimum serum concentration for atezolizumab. |
Measure: | Plasma Concentrations of Total Paclitaxel |
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) |
Safety Issue: | |
Description: | Plasma Concentrations of Total Paclitaxel |
Details
Phase: | Phase 3 |
Primary Purpose: | Interventional |
Overall Status: | Active, not recruiting |
Lead Sponsor: | Hoffmann-La Roche |
Last Updated
August 9, 2021