A Study of Atezolizumab in Combination With Carboplatin Plus (+) Paclitaxel With or Without Bevacizumab Compared With Carboplatin+Paclitaxel+Bevacizumab in Participants With Stage IV Non-Squamous Non-Small Cell Lung Cancer (NSCLC) (IMpower150)

• ClinicalTrials.gov Identifier: NCT02366143
• Recruitment Status: Completed
• First Posted: February 19, 2015
• Results First Posted: October 27, 2020
• Last Update Posted: September 23, 2021
• Sponsor: Hoffmann-La Roche
• Information provided by (Responsible Party): Hoffmann-La Roche

Tracking Information

• First Submitted Date: February 12, 2015
• First Posted Date: February 19, 2015
• Results First Submitted Date: August 21, 2020
• Results First Posted Date: October 27, 2020
• Last Update Posted Date: September 23, 2021
• Actual Study Start Date: March 31, 2015
• Actual Primary Completion Date: September 13, 2019 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 5, 2020)

• Progression Free Survival (PFS), as Determined by the Investigator in Arm B Versus Arm C in the Teff-high WT Population and ITT-WT Population [ Time Frame: Baseline until disease progression or death, whichever occurs first until data cut-off on 15 September 2017 (up to approximately 29 months) ]
  Progression Free Survival (PFS), as Determined by the Investigator using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Arm B versus Arm C in the T-effector (Teff)-high wild type (WT) population and the intent-to-treat (ITT)-WT population.
• Overall Survival (OS) in Arm B Versus Arm C in ITT-WT Population [ Time Frame: Baseline until death until data cut-off on 22 January 2018 (up to approximately 34 months) ]
  Overall Survival (OS) in Arm B Versus Arm C in ITT-WT Population
• Overall Survival (OS) in Arm A Versus Arm C in ITT-WT Population [ Time Frame: Baseline until death (up approximately 53 months) ]
  Overall Survival (OS) in Arm A Versus Arm C in ITT-WT Population

• Original Primary Outcome Measures (submitted: February 12, 2015): Progression Free Survival (PFS) as determined by the Investigator using Response Evaluation Criteria in Solid Tumors (RECIST v1.1) [ Time Frame: up to 2 years ]

Current Secondary Outcome Measures (submitted: August 26, 2021)

• PFS, as Determined by the Independent Review Facility (IRF) in Arm B Versus Arm C in Teff-High-WT Population and ITT-WT Population [ Time Frame: Baseline until disease progression or death, whichever occurs first (up to approximately 29 months) ]
  PFS, as determined by the independent review facility (IRF) Using RECIST v1.1 in Arm B versus Arm C in the T-effector (Teff)-high wild type (WT) population and the intent-to-treat (ITT)-WT population.
• PFS, as Determined by the Investigator in Arm B Versus Arm C in Teff High Population and ITT Population [ Time Frame: Baseline until disease progression or death, whichever occurs first (up to approximately 29 months) ]
  PFS, as determined by the investigator according to RECIST v1.1, in Arm B versus C in the Teff high population and ITT population.
• PFS, as Determined by the Investigator in Arm A Versus Arm B in Teff High-WT Population and ITT-WT Population [ Time Frame: Baseline until disease progression or death, whichever occurs first (up to approximately 29 months) ]
  PFS, as determined by the investigator according to RECIST v1.1, in Arm A versus B in the Teff high-WT population and ITT-WT population.
• PFS, as Determined by the Investigator in Arm B Versus Arm C by PD-L1 Subgroup [ Time Frame: Baseline until disease progression or death, whichever occurs first (up to approximately 29 months) ]
  PFS as Determined by the Investigator according to RECIST v1.1, in Arm B Versus Arm C by PD-L1 Subgroup: TC2/3 or 1C2/3 and TC1/2/3 or IC1/2/3 (ITT-WT Population)
• OS in Arm B Versus Arm C by PD-L1 Subgroup [ Time Frame: Baseline until death (up to approximately 34 months) ]
  OS in Arm B Versus Arm C by PD-L1 Subgroup: TC2/3 or 1C2/3 and TC1/2/3 or IC1/2/3 (ITT-WT Population)
• OS in Arm A Versus Arm C by PD-L1 Subgroup [ Time Frame: Baseline until death (up approximately 53 months) ]
  OS in Arm A Versus Arm C by PD-L1 Subgroup: TC2/3 or 1C2/3 and TC1/2/3 or IC1/2/3 (ITT-WT Population)
• OS in Arm B Versus Arm C in Teff High-WT Population, Teff High Population, and ITT Population [ Time Frame: Baseline until death (up to approximately 34 months) ]
• OS in Arm A Versus Arm C in Teff High-WT Population, Teff High Population, and ITT Population [ Time Frame: Baseline until death (up approximately 53 months) ]
• OS in Arm A Versus Arm B in Teff High-WT Population and ITT-WT Population [ Time Frame: Baseline until death (up approximately 53 months) ]
• Duration of Response (DOR), as Determined By Investigator in Arm B Versus Arm C [ Time Frame: Baseline until disease progression or death, whichever occurs first (up to approximately 29 months) ]
  DOR, as determined by investigator according to RECIST v1.1 in Arm B versus Arm C in the Teff high-WT population and the ITT-WT population.
• Percentage of Participants With an Objective Response (OR) (Complete Response [CR] or Partial Response [PR]) as Determined by the Investigator in the Teff-High-WT Population and ITT-WT Population [ Time Frame: Baseline until disease progression or death, whichever occurs first (up to approximately 29 months) ]
  Percentage of Participants With an Objective Response (OR) (Complete Response [CR] or Partial Response [PR]) as Determined by the Investigator using RECIST v1.1 in the Teff-High-WT population and ITT-WT population.
• OS Rates at Years 1 and 2 in Arm B Versus Arm C [ Time Frame: Baseline to 2 years or death, whichever occurs first. ]
  OS at 1- and 2-year landmark timepoints in Teff-high WT population and ITT-WT population.
• OS Rates at Years 1 and 2 in Arm A Versus Arm C [ Time Frame: Baseline to 2 years or death, whichever occurs first. ]
  OS at 1- and 2-year landmark timepoints in Teff-high WT population and ITT-WT population.
• Time to Deterioration (TTD) in Patient-Reported Lung Cancer Symptoms Determined by European Organization for Research and Treatment of Cancer (EORTC) Quality-of-Life Questionnaire-Core 30 (QLQ-C30) Score [ Time Frame: Baseline up to approximately 29 months ]
  EORTC QLQ-C30 is a validated & reliable self-report measure (Aaronson et al.1993;Fitzsimmons et al.1999) that consists of 30 questions that assess 5 aspects of patient functioning (physical,emotional,role, cognitive,and social), 3 symptom scales (fatigue,nausea & vomiting, pain),global health/quality of life,and six single items (dyspnea,insomnia, appetite loss,constipation,diarrhea, and financial difficulties). EORTC QLQ-C30 is scored according to the EORTC scoring manual (Fayers et al. 2001). All EORTC scales and single-item measures are linearly transformed so that each score has a range of 0-100. A high score for a functional/global health status scale represents a high or healthy level of functioning/HRQoL (Health-Related Quality of Life);however a high score for a symptom scale or item represents a high level of symptomatology or problems. A ≥10-point change in the symptoms subscale score is perceived by patients as clinically significant (Osoba et al.1998).
• TTD in Patient-Reported Lung Cancer Symptoms as Determined by EORTC Quality-of-Life Questionnaire-Core Lung Cancer Module 13 (QLQ-LC13) Score [ Time Frame: Baseline up to approximately 29 months ]
  QLQ-LC13 Quality-of-Life Questionnaire Lung Cancer Module incorporates one multiple-item scale to assess dyspnea and a series of single items assessing pain, coughing, sore mouth, dysphagia, peripheral neuropathy, alopecia, and hemoptysis. The EORTC QLQ-LC13 is scored according to the EORTC scoring manual (Fayers et al. 2001). All EORTC scales and single-item measures are linearly transformed so that each score has a range of 0-100. A high score for a functional/global health status scale represents a high or healthy level of functioning/HRQoL (Health-Related Quality of Life); however, a high score for a symptom scale or item represents a high level of symptomatology or problems. A ≥10-point change in the symptoms subscale score is perceived by patients as clinically significant (Osoba et al. 1998).
• Change From Baseline in Patient-Reported Lung Cancer Symptoms Score Using the Symptoms in Lung Cancer (SILC) Scale [ Time Frame: Baseline up to approximately 29 months ]
  The SILC (Symptoms in Lung Cancer) scale was used to assess patient-reported severity of lung cancer symptoms (chest pain, dyspnea, and cough). The SILC scale is a 9-item content validated self-report measure of lung cancer symptoms. It measures severity of cough, dyspnea, and chest pain with a symptom severity score. The SILC questionnaire comprises three individual symptoms (dyspnea, cough, chest pain) and are scored at the individual symptom level, thus have a dyspnea score, chest pain score, and cough score. Each individual symptom score is calculated as the average of responses for the symptom items [e.g. Chest Pain Score=mean (item 1; item 2)]. An increase in score is suggestive of a worsening in symptomology (i.e. frequency or severity). A score change of ≥0.3 points for the dyspnea and cough symptom scores is considered to be clinically significant; whereas a score change of ≥0.5 points for the chest pain score is considered to be clinically significant.
• Percentage of Participants With Adverse Events [ Time Frame: Baseline up to data cutoff date 7 December 2020 (up to approximately 68 months) ]
  Percentage of participants with at least one adverse event.
• Percentage of Participants With Anti-Therapeutic Antibodies (ATAs) to Atezolizumab [ Time Frame: Baseline up to approximately 29 months ]
• Maximum Observed Serum Concentration (Cmax) of Atezolizumab in Arm A and Arm B [ Time Frame: Day 1 of Cycle 1 and 3 (Cycle length=21 days) ]
  The predose samples will be collected on the same day of treatment administration. The infusion duration of atezolizumab will be of 30-60 minutes.
• Minimum Observed Serum Concentration (Cmin) of Atezolizumab Prior to Infusion in Arm A and Arm B [ Time Frame: Day 21 of Cycles 1, 2 3, and 7 (Cycle length=21 days) ]
• Plasma Concentrations for Carboplatin in Arm A, Arm B, and Arm C [ Time Frame: Predose (same day of treatment administration), 5-10 minutes before end of carboplatin infusion, 1 h after carboplatin infusion (infusion duration=15 to 30 minutes) on D1 of Cy1,3 (Cycle length=21 days) ]
• Plasma Concentrations for Paclitaxel in Arm A, Arm B, and Arm C [ Time Frame: Predose (same day of treatment administration), 5-10 minutes before end of paclitaxel infusion, 1 h after paclitaxel infusion (infusion duration=3 h) on D1 of Cy1,3 (Cycle length=21 days) ]
• Cmax of Bevacizumab in Arm B and Arm C [ Time Frame: Cycle 1 Day 1 and Cycle 3 Day 1 (Cycle length=21 days) ]
• Cmin of Bevacizumab in Arm B and Arm C [ Time Frame: Cycle 1 Day 1 and Cycle 2 Day 21 (Cycle length=21 days) ]

Original Secondary Outcome Measures (submitted: February 12, 2015)

• Objective Response as determined by the Investigator using RECIST v1.1 [ Time Frame: up to 2 years ]
• Overall Survival (OS) [ Time Frame: up to 7 years ]
• Duration of response as determined by the Investigator using RECIST v1.1 [ Time Frame: up to 2 years ]
• PFS as determined by the Independent Review Facility using RECIST v1.1 [ Time Frame: up to 2 years ]
• OS at 1 and 2 Years [ Time Frame: Years 1 and 2 ]
• Time to deterioration (TTD) in patient-reported Lung Cancer Symptoms [ Time Frame: up to 2 years ]
• Change from baseline in patient-reported Lung Cancer Symptoms [ Time Frame: up to 2 years ]
• Safety: Incidence of Adverse Events [ Time Frame: up to 2 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 Carboplatin Plus (+) Paclitaxel With or Without Bevacizumab Compared With Carboplatin+Paclitaxel+Bevacizumab in Participants With Stage IV Non-Squamous Non-Small Cell Lung Cancer (NSCLC)
• Official Title: A Phase III, Open-Label, Randomized Study of Atezolizumab (MPDL3280A, Anti-PD-L1 Antibody) in Combination With Carboplatin+Paclitaxel With or Without Bevacizumab Compared With Carboplatin + Paclitaxel + Bevacizumab in Chemotherapy-Naïve Patients With Stage IV Non-Squamous Non-Small Cell Lung Cancer
• Brief Summary: This randomized, open-label study evaluated the safety and efficacy of atezolizumab (an engineered anti-programmed death-ligand 1 [PD-L1] antibody) in combination with carboplatin+paclitaxel with or without bevacizumab compared with treatment with carboplatin+paclitaxel+bevacizumab in chemotherapy-naïve participants with Stage IV non-squamous NSCLC. Participants were randomized in a 1:1:1 ratio to Arm A (Atezolizumab+Carboplatin+Paclitaxel), Arm B (Atezolizumab+Carboplatin+Paclitaxel+Bevacizumab), or Arm C (Carboplatin+Paclitaxel+Bevacizumab).
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Carcinoma, Non-Small-Cell Lung

Intervention

• Drug: Atezolizumab (MPDL3280A), an engineered anti-PD-L1 antibody
  Atezolizumab was administered as IV infusion at a dose of 1200 milligrams (mg) on Day 1 of each 21-day cycle until loss of clinical benefit.
  Other Names:

  • MPDL3280A
  • RO5541267
  • Tecentriq
• Drug: Bevacizumab
  Bevacizumab was administered as IV infusion at a dose of 15 milligrams per kilogram (mg/kg) on Day 1 of each 21-day cycle until progressive disease, unacceptable toxicity, or death.
• Drug: Carboplatin
  Carboplatin was administered at area under the concentration-time curve (AUC) 6 milligrams per milliliter per minute (mg/mL/min) on Day 1 of each 21-day cycle for 4 or 6 cycles or until loss of clinical benefit whichever occurs first.
• Drug: Paclitaxel
  Paclitaxel was administered as IV infusion at a dose of 200 milligrams per square meter (mg/m^2) on Day 1 of each 21-day cycle for 4 or 6 cycles or until loss of clinical benefit whichever occurs first.

Study Arms

• Experimental: Arm A (Atezolizumab+Paclitaxel+Carboplatin)
  Participants received intravenous (IV) infusion of atezolizumab on Day 1 of each 21-day cycle followed by IV infusion of paclitaxel and carboplatin on Day 1 of each 21-day cycle for 4 or 6 cycles or until loss of clinical benefit whichever occurs first, during induction treatment phase. Participants received IV infusion of atezolizumab during maintenance treatment phase until loss of clinical benefit.
  Interventions:

  • Drug: Atezolizumab (MPDL3280A), an engineered anti-PD-L1 antibody
  • Drug: Carboplatin
  • Drug: Paclitaxel
• Experimental: Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin)
  Participants received IV infusion of atezolizumab and bevacizumab on Day 1 of each 21-day cycle followed by IV infusion of paclitaxel and carboplatin on Day 1 of each 21-day cycle for 4 or 6 cycles or until loss of clinical benefit whichever occurs first, during induction treatment phase. Participants received IV infusion of atezolizumab until loss of clinical benefit and bevacizumab until progressive disease, unacceptable toxicity, or death during maintenance treatment phase.
  Interventions:

  • Drug: Atezolizumab (MPDL3280A), an engineered anti-PD-L1 antibody
  • Drug: Bevacizumab
  • Drug: Carboplatin
  • Drug: Paclitaxel
• Active Comparator: Arm C (Bevacizumab+Paclitaxel+Carboplatin)
  Participants received IV infusion of bevacizumab on Day 1 of each 21-day cycle followed by IV infusion of paclitaxel and carboplatin on Day 1 of each 21-day cycle for 4 or 6 cycles or loss of clinical benefit whichever occurs first, during induction treatment phase. Participants received IV infusion of bevacizumab during maintenance treatment phase until progressive disease, unacceptable toxicity, or death.
  Interventions:

  • Drug: Bevacizumab
  • Drug: Carboplatin
  • Drug: Paclitaxel

Publications *

• Ton TGN, Pal N, Trinh H, Mahrus S, Bretscher MT, Machado RJM, Sadetsky N, Chaudhary N, Lu MW, Riely GJ. Replication of Overall Survival, Progression-Free Survival, and Overall Response in Chemotherapy Arms of Non-Small Cell Lung Cancer Trials Using Real-World Data. Clin Cancer Res. 2022 Jul 1;28(13):2844-2853. doi: 10.1158/1078-0432.CCR-22-0471.
• Nogami N, Barlesi F, Socinski MA, Reck M, Thomas CA, Cappuzzo F, Mok TSK, Finley G, Aerts JG, Orlandi F, Moro-Sibilot D, Jotte RM, Stroyakovskiy D, Villaruz LC, Rodriguez-Abreu D, Wan-Teck Lim D, Merritt D, Coleman S, Lee A, Shankar G, Yu W, Bara I, Nishio M. IMpower150 Final Exploratory Analyses for Atezolizumab Plus Bevacizumab and Chemotherapy in Key NSCLC Patient Subgroups With EGFR Mutations or Metastases in the Liver or Brain. J Thorac Oncol. 2022 Feb;17(2):309-323. doi: 10.1016/j.jtho.2021.09.014. Epub 2021 Oct 7.
• Socinski MA, Nishio M, Jotte RM, Cappuzzo F, Orlandi F, Stroyakovskiy D, Nogami N, Rodriguez-Abreu D, Moro-Sibilot D, Thomas CA, Barlesi F, Finley G, Kong S, Lee A, Coleman S, Zou W, McCleland M, Shankar G, Reck M. IMpower150 Final Overall Survival Analyses for Atezolizumab Plus Bevacizumab and Chemotherapy in First-Line Metastatic Nonsquamous NSCLC. J Thorac Oncol. 2021 Nov;16(11):1909-1924. doi: 10.1016/j.jtho.2021.07.009. Epub 2021 Jul 24.
• Reck M, Wehler T, Orlandi F, Nogami N, Barone C, Moro-Sibilot D, Shtivelband M, Gonzalez Larriba JL, Rothenstein J, Fruh M, Yu W, Deng Y, Coleman S, Shankar G, Patel H, Kelsch C, Lee A, Piault E, Socinski MA. Safety and Patient-Reported Outcomes of Atezolizumab Plus Chemotherapy With or Without Bevacizumab Versus Bevacizumab Plus Chemotherapy in Non-Small-Cell Lung Cancer. J Clin Oncol. 2020 Aug 1;38(22):2530-2542. doi: 10.1200/JCO.19.03158. Epub 2020 May 27.
• Reck M, Mok TSK, Nishio M, Jotte RM, Cappuzzo F, Orlandi F, Stroyakovskiy D, Nogami N, Rodriguez-Abreu D, Moro-Sibilot D, Thomas CA, Barlesi F, Finley G, Lee A, Coleman S, Deng Y, Kowanetz M, Shankar G, Lin W, Socinski MA; IMpower150 Study Group. Atezolizumab plus bevacizumab and chemotherapy in non-small-cell lung cancer (IMpower150): key subgroup analyses of patients with EGFR mutations or baseline liver metastases in a randomised, open-label phase 3 trial. Lancet Respir Med. 2019 May;7(5):387-401. doi: 10.1016/S2213-2600(19)30084-0. Epub 2019 Mar 25.
• Socinski MA, Jotte RM, Cappuzzo F, Orlandi F, Stroyakovskiy D, Nogami N, Rodriguez-Abreu D, Moro-Sibilot D, Thomas CA, Barlesi F, Finley G, Kelsch C, Lee A, Coleman S, Deng Y, Shen Y, Kowanetz M, Lopez-Chavez A, Sandler A, Reck M; IMpower150 Study Group. Atezolizumab for First-Line Treatment of Metastatic Nonsquamous NSCLC. N Engl J Med. 2018 Jun 14;378(24):2288-2301. doi: 10.1056/NEJMoa1716948. Epub 2018 Jun 4.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: April 17, 2017): 1202
• Original Estimated Enrollment (submitted: February 12, 2015): 1200
• Actual Study Completion Date: December 7, 2020
• Actual Primary Completion Date: September 13, 2019 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Eastern Cooperative Oncology Group performance status 0 or 1
• Histologically or cytologically confirmed, Stage IV non-squamous NSCLC
• Participants with no prior treatment for Stage IV non-squamous NSCLC
• Known PD-L1 status as determined by immunohistochemistry assay performed on previously obtained archival tumor tissue or tissue obtained from a biopsy at screening
• Measurable disease as defined by RECIST v1.1
• Adequate hematologic and end organ function

Exclusion Criteria:

Cancer-Specific Exclusions:

• Active or untreated central nervous system metastases
• Malignancies other than NSCLC within 5 years prior to randomization, with the exception of those with a negligible risk of metastasis or death treated with expected curative outcome

General Medical Exclusions:

• Pregnant or lactating women
• History of autoimmune disease
• History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography scan. History of radiation pneumonitis in the radiation field (fibrosis) is permitted
• Positive test for human immunodeficiency virus
• Active hepatitis B or hepatitis C
• Severe infection within 4 weeks prior to randomization
• Significant cardiovascular disease
• Illness or condition that interferes with the participant's capacity to understand, follow and/or comply with study procedures

Exclusion Criteria Related to Medications:

• Prior treatment with cluster of differentiation 137 agonists or immune checkpoint blockade therapies, anti-programmed death-1, and anti-PD-L1 therapeutic antibodies

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, Brazil, Bulgaria, Canada, Chile, France, Germany, Italy, Japan, Latvia, Lithuania, Mexico, Netherlands, Peru, Portugal, Russian Federation, Singapore, Slovakia, Spain, Switzerland, Taiwan, Ukraine, United States

Administrative Information

• NCT Number: NCT02366143
• Other Study ID Numbers: GO29436; 2014-003207-30 ( EudraCT Number )
• Has Data Monitoring Committee: Not Provided
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Hoffmann-La Roche
• Original Responsible Party: Same as current
• Current Study Sponsor: Hoffmann-La Roche
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Clinical Trials; Hoffmann-La Roche

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