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

Purpose

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	Intervention	Phase
Non-Small Cell Lung Cancer	Drug: Atezolizumab Drug: Carboplatin Drug: Cisplatin Drug: Gemcitabine	Phase 3


Study Type:	Interventional
Study Design:	Allocation: Randomized Intervention Model: Parallel Assignment Masking: No masking 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

Resource links provided by NLM:

Genetics Home Reference related topics: lung cancer

MedlinePlus related topics: Lung Cancer

Drug Information available for: Cisplatin Carboplatin Gemcitabine Gemcitabine hydrochloride Atezolizumab

U.S. FDA Resources

Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:

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:

Percentage of Participants With Adverse Events [ Time Frame: From baseline up to approximately 2.5 years ]
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) ]
Overall Survival (OS) [ Time Frame: Baseline up to death (Up to approximately 2.5 years) ]
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 ]
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) ]
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) ]
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) ]
Percentage of Participants Who are Alive at Year 1 and 2 [ Time Frame: Year 1 and 2 ]
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 ]
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 ]
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 ]
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.
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.
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.


Enrollment:	8
Actual Study Start Date:	May 31, 2015
Estimated Study Completion Date:	September 30, 2017
Estimated Primary Completion Date:	September 30, 2017 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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.

Arms

Assigned Interventions

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.

Eligibility


Ages Eligible for Study:	18 Years and older (Adult, Senior)
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

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02409355

Show 82 Study Locations

Sponsors and Collaborators

Hoffmann-La Roche

Investigators


Study Director:	Clinical Trials	Hoffmann-La Roche

More Information


Responsible Party:	Hoffmann-La Roche
ClinicalTrials.gov Identifier:	NCT02409355 History of Changes
Other Study ID Numbers:	GO29432 2014-003106-33 ( EudraCT Number )
Study First Received:	April 1, 2015
Last Updated:	July 3, 2017

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 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

ClinicalTrials.gov processed this record on July 28, 2017