A Study of Atezolizumab Compared With a Single-Agent Chemotherapy in Treatment Naïve Participants With Locally Advanced or Recurrent or Metastatic Non-Small Cell Lung Cancer Who Are Deemed Unsuitable For Platinum-Doublet Chemotherapy (IPSOS)

• ClinicalTrials.gov Identifier: NCT03191786
• Recruitment Status: Completed
• First Posted: June 19, 2017
• Results First Posted: May 17, 2023
• Last Update Posted: November 7, 2023
• Sponsor: Hoffmann-La Roche
• Information provided by (Responsible Party): Hoffmann-La Roche

Tracking Information

• First Submitted Date: June 15, 2017
• First Posted Date: June 19, 2017
• Results First Submitted Date: April 18, 2023
• Results First Posted Date: May 17, 2023
• Last Update Posted Date: November 7, 2023
• Actual Study Start Date: September 11, 2017
• Actual Primary Completion Date: April 30, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 18, 2023)

Overall Survival (OS) [ Time Frame: From randomization up to death from any cause (up to approximately 55 months) ]

Overall survival is defined as the time between the date of randomization and the date of death due to any cause.

• Original Primary Outcome Measures (submitted: June 15, 2017): Overall Survival [ Time Frame: From randomization up to death from any cause (up to approximately 3.5 years) ]

Current Secondary Outcome Measures (submitted: April 18, 2023)

• OS Rates at the 6, 12, 18, 24-Months Timepoints [ Time Frame: 6, 12, 18 and 24 months ]
  OS rate at 6, 12, 18 and 24 months were estimated for each treatment arm.
• Percentage of Participants With Objective Response Rate, as Determined by the Investigator Using Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1 (v1.1) [ Time Frame: From randomization to the first occurence of disease progression or death from any cause, whichever occurs first (up to approximately 55 months) ]
  Objective response rate (ORR) is defined as a Best Overall Response (BOR) of either Complete Response (CR) or Partial Response (PR), as determined by the investigator with use of RECIST v1.1. A minimum interval of 6 weeks (42 days) will be considered for Stable Disease (SD) to be assigned as best overall response, i.e. in the case the single response is SD, PR or CR, this single response must have been assessed no less than 6 weeks (at least 42 days) after start date of study treatment.
• Progression-Free Survival (PFS), as Determined by the Investigator Using RECIST v1.1 [ Time Frame: From randomization to the first occurence of disease progression or death from any cause, whichever occurs first (up to approximately 55 months) ]
  PFS is defined as the time from randomization to the first documented disease progression as determined by the investigator with the use of RECIST v1.1 or death from any cause, whichever occurs first.
• Duration of Response (DOR), as Determined by the Investigator Using RECIST v1.1 [ Time Frame: Time from the first occurrence of a documented objective response to the time of disease progression or death from any cause, whichever occurs first (up to approximately 55 months) ]
  DOR is defined as the time from the first tumor assessment that supports the participants' objective response (CR or PR, whichever is first reported) to documented disease progression as determined by the investigator according to RECIST v1.1 or death from any cause, whichever occurs first, among patients who have a best overall response as CR or PR.
• Percentage of Participants With At Lease One Adverse Event [ Time Frame: From randomization up to approximately 55 months ]
  Percentage of participants with at least one adverse event.
• Change From Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 (EORTC-QLQ-C30) Score [ Time Frame: Baseline, Day 1 of each treatment cycle up to 30 days after last dose (up to approximately 55 months) (Cycle length = 21 days) ]
  EORTC QLQ-C30 is a validated and reliable self-report measure that consists of 30 questions that assess five aspects of patient functioning (physical, emotional, role, cognitive, and social), three symptom scales (fatigue, nausea and 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 participants as clinically significant (Osoba et al. 1998).
• Change From Baseline in EORTC QLQ Supplementary Lung Cancer Module 13 (EORTC QLQ-LC13) Score [ Time Frame: Baseline, Day 1 of each treatment cycle up to 30 days after last dose (up to approximately 55 months) (Cycle length = 21 days) ]
  The EORTC QLQ-LC13 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 participants as clinically significant (Osoba et al. 1998).
• Time to Deterioration (TTD) in Patient-Reported Lung Cancer Symptoms as Assessed by EORTC QLQ-C30 Score [ Time Frame: From baseline up to approximately 55 months ]
  TTD with use of the EORTC is defined as the time from randomization to the first confirmed clinically meaningful deterioration in EORTC symptom scores. Confirmed clinically meaningful deterioration in lung cancer symptoms is defined as a = 10-point increase above baseline in a symptom score that must be held for at least two consecutive assessments or an initial = 10-point increase above baseline followed by either (a) death within 6 weeks from the last assessment through Week 48 or (b) death within 9 weeks from the last assessment from Week 48 thereafter. A = 10-point change in the EORTC scale score is perceived by participants as clinically significant (Osoba et al. 1998).
• Time to Deterioration in Patient-Reported Lung Cancer Symptoms As Assessed by EORTC QLQ-LC13 Score [ Time Frame: From baseline up to approximately 55 months ]
  TTD with use of the EORTC is defined as the time from randomization to the first confirmed clinically meaningful deterioration in EORTC symptom scores. Confirmed clinically meaningful deterioration in lung cancer symptoms is defined as a = 10-point increase above baseline in a symptom score that must be held for at least two consecutive assessments or an initial = 10-point increase above baseline followed by either (a) death within 6 weeks from the last assessment through Week 48 or (b) death within 9 weeks from the last assessment from Week 48 thereafter. A = 10-point change in the EORTC scale score is perceived by participants as clinically significant.
• Overall Survival in Participants With PD-L1 Positive Status [ Time Frame: From randomization up to death from any cause (up to approximately 55 months) ]
  Overall survival will be assessed in participants whose tumors express PD-L1 protein as measured by PD-L1 SP263 IHC assay.
• Progression-Free Survival (PFS), as Determined by the Investigator Using RECIST v1.1 in Participants With PD-L1 Positive Status [ Time Frame: From randomization to the first occurence of disease progression or death from any cause, whichever occurs first (up to approximately 55 months) ]
  Investigator-assessed PFS according to RECIST v1.1 assessed in participants whose tumors express PD-L1 protein as measured by PD-L1 SP263 IHC assay.

Original Secondary Outcome Measures (submitted: June 15, 2017)

• Percentage of Participants Who Are Alive at Specified Timepoints [ Time Frame: 6, 12, 18 and 24 months ]
• Percentage of Participants With Objective Response, as Determined by the Investigator Using Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1 (v1.1) [ Time Frame: From randomization to the first occurence of disease progression or death from any cause, whichever occurs first (up to approximately 3.5 years) ]
  Objective response is defined as partial response (PR) plus complete response (CR).
• Progression-Free Survival (PFS), as Determined by the Investigator Using RECIST v1.1 [ Time Frame: From randomization to the first occurence of disease progression or death from any cause, whichever occurs first (up to approximately 3.5 years) ]
• Duration of Response, as Determined by the Investigator Using RECIST v1.1 [ Time Frame: Time from the first occurrence of a documented objective response to the time of disease progression or death from any cause, whichever occurs first (up to approximately 3.5 years) ]
• Percentage of Participants With Adverse Events (AEs) [ Time Frame: From randomization up to approximately 3.5 years ]
• Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ) - Core 30 (C30) (EORTC-QLQ-C30) Score [ Time Frame: Baseline, Day 1 of each treatment cycle up to 30 days after last dose (up to approximately 3.5 years) (Cycle length = 21 days) ]
• Change From Baseline in EORTC QLQ Supplementary Lung Cancer Module 13 (LC13) (EORTC QLQ-LC13) Score [ Time Frame: Baseline, Day 1 of each treatment cycle up to 30 days after last dose (up to approximately 3.5 years) (Cycle length = 21 days) ]
• Time to Deterioration in Patient-Reported Lung Cancer Symptoms as Assessed by EORTC QLQ-C30 Score [ Time Frame: From baseline up to approximately 3.5 years ]
• Time to Deterioration in Patient-Reported Lung Cancer Symptoms As Assessed by EORTC QLQ-LC13 Score [ Time Frame: From baseline up to approximately 3.5 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 Compared With a Single-Agent Chemotherapy in Treatment Naïve Participants With Locally Advanced or Recurrent or Metastatic Non-Small Cell Lung Cancer Who Are Deemed Unsuitable For Platinum-Doublet Chemotherapy
• Official Title: A Phase III, Open-Label, Multicenter, Randomized Study to Investigate the Efficacy and Safety of Atezolizumab Compared With Chemotherapy in Patients With Treatment Naïve Advanced or Recurrent (Stage IIIb Not Amenable for Multimodality Treatment) or Metastatic (Stage IV) Non-Small Cell Lung Cancer Who Are Deemed Unsuitable for Platinum-Containing Therapy
• Brief Summary: This Phase III, global, multicenter, open-label, randomized, controlled study will evaluate the efficacy and safety of atezolizumab (an anti-programmed death-ligand 1 [anti-PD-L1] antibody) compared with a single agent chemotherapy regimen by investigator choice (vinorelbine or gemcitabine) in treatment-naïve participants with locally advanced or metastatic non-small cell lung cancer (NSCLC) who are deemed unsuitable for any platinum-doublet chemotherapy due to poor performance status (Eastern Cooperative Oncology Group [ECOG] performance status of 2-3).
• 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: Non-Small Cell Lung Cancer

Intervention

• Drug: Atezolizumab (MPDL3280A), an engineered anti-PD-L1 antibody
  Atezolizumab will be administered via IV infusion once every three weeks (QW3).
  Other Name: MPDL3280A
• Drug: Vinorelbine
  Vinorelbine will be administered per relevant local guidelines and Summary of Product Characteristics (SmPC) management.
  Other Name: Navelbine®
• Drug: Gemcitabine
  Gemcitabine will be administered per relevant local guidelines and SmPC management.
  Other Name: Gemzar®

Study Arms

• Experimental: Atezolizumab
  Participants will receive atezolizumab 1200 milligrams (mg) intravenous (IV) infusion on Day 1 of each 21-day cycle until loss of clinical benefit, unacceptable toxicity, participant or physician decision to discontinue, or death.
  Intervention: Drug: Atezolizumab (MPDL3280A), an engineered anti-PD-L1 antibody
• Active Comparator: Single Agent Chemotherapy (Vinorelbine or Gemcitabine)
  Participants will receive single agent chemotherapy; either vinorelbine oral or IV, or gemcitabine IV, according to the label based on investigator's choice.
  Interventions:

  • Drug: Vinorelbine
  • Drug: Gemcitabine

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: May 8, 2020): 453
• Original Estimated Enrollment (submitted: June 15, 2017): 441
• Actual Study Completion Date: October 25, 2023
• Actual Primary Completion Date: April 30, 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Histologically or cytologically confirmed diagnosis of advanced or recurrent (Stage IIIB not amenable for multimodality treatment) or metastatic (Stage IV) NSCLC as per the American Joint Committee on Cancer (AJCC) 7th edition
• No sensitizing epidermal growth factor receptor (EGFR) mutation (L858R or exon 19 deletions) or anaplastic lymphoma kinase (ALK) fusion oncogene detected
• No prior systemic treatment for advanced or recurrent (Stage IIIB not amenable for multimodality treatment) or metastatic (Stage IV) NSCLC as per the AJCC 7th edition
• Life expectancy greater than or equal to (>/=) 8 weeks
• Deemed unsuitable by the investigator for any platinum-doublet chemotherapy due to poor performance status (ECOG performance status of 2-3). However, participants >= 70 years of age who have an ECOG PS of 0 or 1 may be included due to: a) substantial comorbidities; b) contraindication(s) for any platinum-doublet chemotherapy
• Representative formalin-fixed paraffin-embedded (FPPE) tumor tissue block obtained during course of disease (archival tissue) or at screening
• Participants with treated, asymptomatic central nervous system (CNS) metastases are eligible, provided they meet all of the following criteria: Measurable disease outside CNS; Only supratentorial and cerebellar metastases allowed; No ongoing requirement for corticosteroids as therapy for CNS disease; No stereotactic radiation within 7 days or whole-brain radiation within 14 days prior to randomization; No evidence of interim progression between the completion of CNS-directed therapy and the screening radiographic study
• Adequate hematologic and end organ function
• Female participants of childbearing potential randomized to the atezolizumab treatment arm agree to use protocol defined methods of contraception

Exclusion Criteria:

Cancer-Specific Exclusion Criteria:

• Participants younger than 70 years who have an ECOG performance status of 0 or 1
• Active or untreated CNS metastases as determined by computed tomography (CT) or magnetic resonance imaging (MRI) evaluation of the brain during screening and prior radiographic assessments
• Uncontrolled tumor-related pain
• Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently)
• Uncontrolled or symptomatic hyerpcalcemia (ionized calcium > 1.5 mmol/L or calcium >12 mg/dL or corrected serum calcium >ULN)
• History of other malignancy within 5 years prior to screening, with the exception of those with a negligible risk of metastasis or death treated with expected curative outcome
• National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0 (v4.0) Grade 3 or higher toxicities due to any prior therapy (example [e.g.], radiotherapy) (excluding alopecia), which have not shown improvement and are strictly considered to interfere with current study medication
• Participants who have received prior neo-adjuvant, adjuvant chemotherapy, radiotherapy, or chemoradiotherapy with curative intent for non-metastatic disease must have experienced a treatment-free interval of at least 6 months from randomization since the last chemotherapy, radiotherapy, or chemoradiotherapy

General Medical Exclusion Criteria:

• History of autoimmune disease except autoimmune-related hypothyroidism and controlled Type I diabetes mellitus
• History of idiopathic pulmonary fibrosis (IPF), organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis
• Known positivity for human immunodeficiency virus (HIV)
• Known active hepatitis B or hepatitis C
• Active tuberculosis
• Severe infections within 4 weeks prior to randomization
• Significant cardiovascular disease, such as New York Heart Association (NYHA) cardiac disease (Class II or greater), myocardial infarction within 3 months prior to randomization, unstable arrhythmias, or unstable angina
• Major surgical procedure other than for diagnosis within 4 weeks prior to randomization or anticipation of need for a major surgical procedure during the course of the study
• Prior allogeneic bone marrow transplantation or solid organ transplant
• Participants with an illness or condition that may interfere with capacity or compliance with the study protocol, as per investigator's judgment
• Treatment with any other investigational agent or participation in another clinical study with therapeutic intent within 28 days prior to randomization

Exclusion Criteria Related to Atezolizumab:

• History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
• Known hypersensitivity to biopharmaceuticals produced in Chinese hamster ovary cells or any component of the atezolizumab formulation
• Oral or IV antibiotic treatment
• Administration of a live, attenuated vaccine within 4 weeks before randomization or anticipation that such a live attenuated vaccine will be required during the study
• Prior treatment with cluster of differentiation 137 (CD137) agonists or immune checkpoint blockade therapies, anti-programmed death-1 (anti-PD-1), and anti-PD-L1 therapeutic antibodies
• Treatment with systemic immunostimulatory agents within 4 weeks or 5 half-lives of the drug, whichever is shorter, prior to randomization
• Treatment with systemic corticosteroids or other immunosuppressive medications
• Participants not willing to stop treatment with traditional herbal medicines

Exclusion Criteria Related to Chemotherapy:

• Known sensitivity and contraindications to the 2 comparative chemotherapy agents (that is [i.e.] vinorelbine, oral or intravenous, and gemcitabine, intravenous)

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, Belgium, Brazil, Bulgaria, Canada, China, Colombia, Czechia, Denmark, Germany, India, Ireland, Italy, Kazakhstan, Luxembourg, Mexico, Poland, Portugal, Romania, Slovakia, Spain, Switzerland, United Kingdom, Vietnam
• Removed Location Countries: Swaziland

Administrative Information

• NCT Number: NCT03191786
• Other Study ID Numbers: MO29872; 2015-004105-16 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes

• 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: November 2023