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)

• ClinicalTrials.gov Identifier: NCT02425891
• Recruitment Status: Active, not recruiting
• First Posted: April 24, 2015
• Last Update Posted: February 11, 2021
• Sponsor: Hoffmann-La Roche
• Information provided by (Responsible Party): Hoffmann-La Roche

Tracking Information

• First Submitted Date: April 21, 2015
• First Posted Date: April 24, 2015
• Last Update Posted Date: February 11, 2021
• Actual Study Start Date: June 23, 2015
• Actual Primary Completion Date: April 14, 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 23, 2017)

• 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 53 months (assessed at Screening, every 8 weeks for the first 12 months, thereafter every 12 weeks until disease progression or death, whichever occurs first) ]
• PFS According to RECIST v1.1 in Participants with Detectable Programmed Death-Ligand 1 (PD-L1) [ Time Frame: Baseline up to 53 months (assessed at Screening, every 8 weeks for the first 12 months, thereafter every 12 weeks until disease progression or death, whichever occurs first) ]
• Overall Survival (OS) in all Randomized Participants [ Time Frame: Baseline until death due to any cause (up to 53 months) ]
• OS in Participants with Detectable PD-L1 [ Time Frame: Baseline until death due to any cause (up to 53 months) ]

• Original Primary Outcome Measures (submitted: April 21, 2015): Progression Free Survival (PFS), defined as the time from randomization to the time of radiographic progression or death from any cause during the study for both the Intent To Treat (ITT) population and the PD-L1-positive subpopulations [ Time Frame: Approximately 22 months ]

Current Secondary Outcome Measures (submitted: March 23, 2017)

• 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 53 months (assessed at Screening, every 8 weeks for the first 12 months, thereafter every 12 weeks until disease progression or death, whichever occurs first) ]
• 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 53 months (assessed at Screening, every 8 weeks for the first 12 months, thereafter every 12 weeks until disease progression or death, whichever occurs first) ]
• Duration of Response (DOR) According to RECIST v1.1 in all Randomized Participants [ Time Frame: Baseline up to 53 months (assessed at Screening, every 8 weeks for the first 12 months, thereafter every 12 weeks until disease progression or death, whichever occurs first) ]
• DOR Acccording to RECIST v1.1 in Participants with Detectable PD-L1 [ Time Frame: Baseline up to 53 months (assessed at Screening, every 8 weeks for the first 12 months, thereafter every 12 weeks until disease progression or death, whichever occurs 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 [ Time Frame: Baseline up to 53 months (assessed at Day 1 of each cycle up to treatment discontinuation [approximately 53 months], every 28 days after treatment discontinuation for 1 year [overall approximately 53 months]) (cycle = 28 days) ]
• 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 53 months (assessed at Day 1 of each cycle up to treatment discontinuation [approximately 53 months], every 28 days after treatment discontinuation for 1 year [overall approximately 53 months]) (cycle = 28 days) ]
• Percentage of Participants with Adverse Events (AEs) or Serious AEs (SAEs) [ Time Frame: Baseline up to 53 months ]
• Percentage of Participants with Anti-Therapeutic Antibodies (ATAs) Against Atezolizumab [ Time Frame: Baseline up to 53 months (assessed at pre-dose [Hour 0] on Day 1 of Cycles 1, 2, 3, 4, 8, 16, and every 8 cycles thereafter up to treatment discontinuation [approximately 53 months], 120 days after last dose [approximately 53 months]) (Cycle = 28 days) ]
• Maximum Serum Concentration (Cmax) for Atezolizumab [ Time Frame: Pre-dose (Hour 0) on Cycle 1 Day 1 up to 53 months (detailed timeframe is provided in outcome description section) ]
  Pre-dose (Hour 0), 30 minutes after end of atezolizumab infusion (infusion duration = 60 minutes) on Cycle 1 Day 1; pre-dose (Hour 0) on Day 1 of Cycles 2, 3, 4, 8, 16, and every 8 cycles thereafter up to treatment discontinuation (approximately 53 months), 120 days after last dose (approximately 53 months) (Cycle = 28 days)
• Minimum Serum Concentration (Cmin) for Atezolizumab [ Time Frame: Pre-dose (Hour 0) on Cycle 1 Day 1 up to 53 months (detailed timeframe is provided in outcome description section) ]
  Pre-dose (Hour 0), 30 minutes after end of atezolizumab infusion (infusion duration = 60 minutes) on Cycle 1 Day 1; pre-dose (Hour 0) on Day 1 of Cycles 2, 3, 4, 8, 16, and every 8 cycles thereafter up to treatment discontinuation (approximately 53 months), 120 days after last dose (approximately 53 months) (Cycle = 28 days)
• 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) ]

Original Secondary Outcome Measures (submitted: April 21, 2015)

• Overall Survival, defined as the time from the date of randomization to the date of death from any cause for both Intent to Treat population and PD-L1-positive subpopulation [ Time Frame: Approximately 3.6 years ]
• Objective Response Rate for both Intent to Treat population and PD-L1-positive subpopulation [ Time Frame: Approximately 3.6 years ]
• Duration of Objective Response (DOR) defined as time from first occurrence of a documented objective tumor response to time of radiographic progression (per investigator using RECIST v1.1) or death from any cause on study, whichever occurs first [ Time Frame: Approximately 3.6 years ]
• Time to deterioration (TTD) in global health status/HRQoL, defined by a minimally important decrease of > or = 10 points on the global health status/HRQoL scale of the EORTC QLQ-C30 [ Time Frame: Approximately 3.6 years ]
• Incidence, nature, and severity of adverse events graded according to NCI CTCAE v4.0 [ Time Frame: Approximately 3.6 years ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• 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
• Brief Summary: This multicenter, randomized, double-blind study will evaluate 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 Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Triple Negative Breast Cancer

Intervention

• Drug: Atezolizumab (MPDL3280A), an engineered anti-PDL1 antibody
  Atezolizumab at a fixed dose of 840 milligrams via intravenous (IV) infusion on Days 1 and 15 of each 28-day cycle until disease progression or unacceptable toxicity.
  Other Name: Tecentriq, MPDL3280A
• Drug: Nab-Paclitaxel
  Nab-Paclitaxel at a starting dose of 100 milligrams per square meter via IV infusion on Days 1, 8, and 15 of each 28-day cycle. Nab-Paclitaxel will be administered for a target of at least 6 cycles, with no maximum in the absence of disease progression or unacceptable toxicity.
  Other Name: Abraxane®
• Drug: Placebo
  Placebo administered via IV infusion on Days 1 and 15 of each 28-day cycle until disease progression or unacceptable toxicity.

Study Arms

• Experimental: Atezolizumab Plus Nab-Paclitaxel
  Participants assigned to atezolizumab plus nab-paclitaxel will receive both agents until disease progression or unacceptable toxicity.
  Interventions:

  • Drug: Atezolizumab (MPDL3280A), an engineered anti-PDL1 antibody
  • Drug: Nab-Paclitaxel
• Placebo Comparator: Placebo Plus Nab-Paclitaxel
  Participants assigned to placebo plus nab-paclitaxel will receive both agents until disease progression or unacceptable toxicity.
  Interventions:

  • Drug: Nab-Paclitaxel
  • Drug: Placebo

Publications *

• Adams S, Diéras V, Barrios CH, Winer EP, Schneeweiss A, Iwata H, Loi S, Patel S, Henschel V, Chui SY, Rugo HS, Emens LA, Schmid P. Patient-reported outcomes from the phase III IMpassion130 trial of atezolizumab plus nab-paclitaxel in metastatic triple-negative breast cancer. Ann Oncol. 2020 May;31(5):582-589. doi: 10.1016/j.annonc.2020.02.003. Epub 2020 Feb 20.
• Schmid P, Rugo HS, Adams S, Schneeweiss A, Barrios CH, Iwata H, Diéras V, Henschel V, Molinero L, Chui SY, Maiya V, Husain A, Winer EP, Loi S, Emens LA; IMpassion130 Investigators. Atezolizumab plus nab-paclitaxel as first-line treatment for unresectable, locally advanced or metastatic triple-negative breast cancer (IMpassion130): updated efficacy results from a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2020 Jan;21(1):44-59. doi: 10.1016/S1470-2045(19)30689-8. Epub 2019 Nov 27.
• Schmid P, Adams S, Rugo HS, Schneeweiss A, Barrios CH, Iwata H, Diéras V, Hegg R, Im SA, Shaw Wright G, Henschel V, Molinero L, Chui SY, Funke R, Husain A, Winer EP, Loi S, Emens LA; IMpassion130 Trial Investigators. Atezolizumab and Nab-Paclitaxel in Advanced Triple-Negative Breast Cancer. N Engl J Med. 2018 Nov 29;379(22):2108-2121. doi: 10.1056/NEJMoa1809615. Epub 2018 Oct 20.

Recruitment Information

• Recruitment Status: Active, not recruiting
• Estimated Enrollment (submitted: February 23, 2016): 900
• Original Estimated Enrollment (submitted: April 21, 2015): 350
• Estimated Study Completion Date: July 30, 2021
• Actual Primary Completion Date: April 14, 2020 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Argentina, Australia, Austria, Belgium, Bosnia and Herzegovina, Brazil, Canada, Chile, Colombia, Costa Rica, Czechia, Estonia, Finland, France, Germany, Greece, Guatemala, Hong Kong, Hungary, Italy, Japan, Korea, Republic of, Latvia, Mexico, Norway, Panama, Poland, Romania, Russian Federation, Serbia, Singapore, Slovenia, Spain, Sweden, Switzerland, Taiwan, Thailand, Turkey, Ukraine, United Kingdom, United States
• Removed Location Countries: Czech Republic, Denmark, Portugal

Administrative Information

• NCT Number: NCT02425891
• Other Study ID Numbers: WO29522; 2014-005490-37 ( EudraCT Number )
• Has Data Monitoring Committee: Not Provided
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Hoffmann-La Roche
• Study Sponsor: Hoffmann-La Roche
• Collaborators: Not Provided

Investigators

• Study Director: Clinical Trials; Hoffmann-La Roche

• PRS Account: Hoffmann-La Roche
• Verification Date: February 2021