A Study of Atezolizumab Compared With Gemcitabine Plus (+) Cisplatin or Carboplatin in Participants With Stage IV Squamous Non-Small Cell Lung Cancer (NSCLC) (IMpower111)

Study Description

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Brief Summary:

This randomized, open-label study is designed to evaluate and compare the safety and efficacy of atezolizumab with gemcitabine + cisplatin or carboplatin in participants with chemotherapy-naive, Stage IV squamous NSCLC.

Condition or disease	Intervention/treatment	Phase
Non-Small Cell Lung Cancer	Drug: Atezolizumab; Drug: Carboplatin; Drug: Cisplatin; Drug: Gemcitabine	Phase 3

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	8 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	A Phase III, Open-Label, Randomized Study of Atezolizumab (Anti-PD-L1 Antibody) Compared With Gemcitabine+Cisplatin or Carboplatin for PD-L1-Selected, Chemotherapy Naive Patients With Stage IV Squamous Non-Small Cell Lung Cancer
Actual Study Start Date :	May 31, 2015
Actual Primary Completion Date :	December 7, 2017
Actual Study Completion Date :	December 7, 2017

Arms and Interventions

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Arm	Intervention/treatment
Experimental: Atezolizumab; Participants will receive intravenous (IV) infusion of atezolizumab once on Day 1 of each 21-day cycle until loss of clinical benefit.	Drug: Atezolizumab; Atezolizumab will be administered at a dose of 1200 milligrams (mg) by IV infusion on Day 1 of each 21-day cycle until loss of clinical benefit.; Other Name: MPDL3280A; Tecentriq
Active Comparator: Gemcitabine + Cisplatin/Carboplatin; Participants will receive IV infusion of gemcitabine + cisplatin or gemcitabine + carboplatin once on Day 1 of each 21-day cycle for four or six cycles as per local standard of care.	Drug: Carboplatin; Carboplatin will be administered at area under the concentration-time curve (AUC) 5 IV infusion once on Day 1 of each 21-day cycle for 4 or 6 cycles.; Drug: Cisplatin; Cisplatin will be administered at 75 milligrams per square meter (mg/m^2) IV infusion once on Day 1 of each 21-day cycle for 4 or 6 cycles.; Drug: Gemcitabine; Gemcitabine will be administered at 1000 mg/m^2 (when coadministered with carboplatin) or 1250 mg/m^2 (when coadministered with cisplatin) IV infusion on Days 1 and 8 of each 21-day cycle for 4 or 6 cycles.

Outcome Measures

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Primary Outcome Measures :

1. Progression-Free Survival (PFS) as Determined by the Investigator Using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) [ Time Frame: Baseline up to death or disease progression, whichever occurs first (up to approximately 2.5 years) ]

Secondary Outcome Measures :

1. Percentage of Participants With Adverse Events [ Time Frame: From baseline up to approximately 2.5 years ]
2. Percentage of Participants With an Objective Response (Complete Response [CR] Plus Partial Response [PR]) as Assessed by the Investigator Using RECIST v1.1 [ Time Frame: Baseline up to death or disease progression, whichever occurs first (Up to approximately 2.5 years) ]
3. Overall Survival (OS) [ Time Frame: Baseline up to death (Up to approximately 2.5 years) ]
4. Time to Deterioration (TTD) in Patient-Reported Lung Cancer Symptoms as Assessed by the Symptoms in Lung Cancer (SILC) Scale Symptom Score [ Time Frame: Baseline up to approximately 2.5 years ]
5. PFS as Determined by an Independent Review Facility (IRF) Using RECIST v1.1 [ Time Frame: Baseline up to death or disease progression, whichever occurs first (up to approximately 2.5 years) ]
6. Duration of Response (DOR) as Determined by the Investigator Using RECIST v1.1 [ Time Frame: Baseline up to death or disease progression, whichever occurs first (up to approximately 2.5 years) ]
7. Time in Response (TIR) as Determined by the Investigator Using RECIST v1.1 [ Time Frame: Baseline up to death or disease progression, whichever occurs first (up to approximately 2.5 years) ]
8. Percentage of Participants Who are Alive at Year 1 and 2 [ Time Frame: Year 1 and 2 ]
9. TTD in Patient-Reported Lung Cancer Symptoms as Assessed by European Organization for Research and Treatment of Cancer (EORTC) Quality of Life-Core 30 (QLQ-C30) Questionnaire Score [ Time Frame: Baseline up to approximately 2.5 years ]
10. TTD in Patient-Reported Lung Cancer Symptoms as Assessed by EORTC Quality of Life-Core Lung Cancer Module 13 (QLQ-C13) Questionnaire Score [ Time Frame: Baseline up to approximately 2.5 years ]
11. Change From Baseline in Patient-Reported Lung Cancer Symptoms on the Symptom Severity Score of the SILC Scale [ Time Frame: Baseline up to approximately 2.5 years ]
12. Pharmacokinetics: Minimum Observed Serum Concentration (Cmin) of Atezolizumab [ Time Frame: Predose on Day 1 of Cycles (Cy) 2, 3, 4, 8, 16, and every 8 cycles thereafter (cycle length=21 days), at treatment discontinuation, and at 120 days after the last dose of atezolizumab (up to approximately 2.5 years) ]
    Predose samples will be collected prior to dosing on the same day of treatment administration.
13. Pharmacokinetics: Maximum Observed Serum Concentration (Cmax) of Atezolizumab [ Time Frame: Predose on Day 1 of Cy2,3,4,8,16, and every 8 cycles thereafter (cycle length=21 days), 0.5 hour post-infusion on Day 1 of Cycle 1, at treatment discontinuation, and at 120 days after the last dose of atezolizumab (up to approximately 2.5 years) ]
    Predose samples will be collected prior to dosing on the same day of treatment administration. The infusion duration will be of 60 minutes for first infusion and will be reduced to 30 minutes if the participant tolerated the first infusion well without infusion-associated adverse events.
14. Percentage of Participants With Anti-Therapeutic Antibody (ATA) to Atezolizumab [ Time Frame: Predose on Day 1 of Cy2,3,4,8,16, and every 8 cycles thereafter (cycle length=21 days), at treatment discontinuation, and at 120 days after the last dose of atezolizumab (up to approximately 2.5 years) ]
    Predose samples will be collected prior to dosing on the same day of treatment administration.

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

• Histologically or cytologically confirmed Stage IV squamous NSCLC
• Tumor programmed death-ligand 1 (PD-L1) expression, as determined by immunohistochemistry (IHC) assay of archival tumor tissue or tissue obtained at screening
• No prior treatment for Stage IV squamous NSCLC
• Measurable disease as defined by RECIST v1.1
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
• Adequate hematologic and end-organ function

Exclusion Criteria:

• Active or untreated central nervous system (CNS) metastases
• Untreated or inadequately treated spinal cord compression
• Leptomeningeal disease
• Uncontrolled pleural effusion, pericardial effusion, or ascites
• Uncontrolled tumor-related pain
• Uncontrolled hypercalcemia
• Any other malignancies within 5 years except those with negligible risk of metastasis or death
• Pregnant or lactating women
• Known hypersensitivity to any component of atezolizumab formulation or other study medication
• History of autoimmune disease except controlled, treated hypothyroidism or type I diabetes
• Prior allogeneic bone marrow or solid organ transplantation
• Positive human immunodeficiency virus (HIV) test
• Active hepatitis B or C
• Active tuberculosis
• Significant cardiovascular disease
• Severe infection or major surgery within 4 weeks prior to randomization
• Use of any approved anti-cancer therapy within 3 weeks prior to treatment
• Use of an investigational agent or participation in another clinical trial within 4 weeks prior to randomization
• Exposure to oral or IV antibiotics within 2 weeks or live attenuated vaccines within 4 weeks prior to randomization
• Prior treatment with cluster of differentiation (CD) 137 agonists or immune checkpoint blockade therapies, anti-programmed death-1 (anti-PD-1), and anti-PD-L1 therapeutic antibodies
• Treatment with immunostimulatory agents within 4 weeks or immunosuppressive agents within 2 weeks prior to randomization

Contacts and Locations

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Sponsors and Collaborators

Hoffmann-La Roche

Investigators

Study Director:	Clinical Trials	Hoffmann-La Roche

More Information

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Responsible Party:	Hoffmann-La Roche
ClinicalTrials.gov Identifier:	NCT02409355 History of Changes
Other Study ID Numbers:	GO29432; 2014-003106-33 ( EudraCT Number )
First Posted:	April 6, 2015
Last Update Posted:	February 13, 2018
Last Verified:	February 2018

Additional relevant MeSH terms:

Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Gemcitabine; Atezolizumab; Cisplatin	Carboplatin; Antibodies, Monoclonal; Antineoplastic Agents; Antimetabolites, Antineoplastic; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Antiviral Agents; Anti-Infective Agents; Enzyme Inhibitors; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs