Clinical trial NCT01846416: A Study of Atezolizumab in Participants With Programmed Death-Ligand 1 (PD-L1) Positive Locally Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC) [FIR]
Official title: A Phase II, Multicenter, Single-arm Study of MPDL3280A in Patients With PD-L1-Positive Locally Advanced or Metastatic Non-small Cell Lung Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Non-Small Cell Lung Cancer
Lead sponsor: Genentech, Inc.
Sponsor class: INDUSTRY
First posted: 2013-05-03
Enrollment: 138
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This multicenter, single-arm study will evaluate the efficacy and safety of atezolizumab (MPDL3280A) in participants with PD-L1-positive locally advanced or metastatic NSCLC. Participants will receive an intravenous (IV) dose of 1200 milligrams (mg) atezolizumab (MPDL3280A) on Day 1 of 21-day cycles until disease progression.

Eligible participants will be categorized in to three groups as follows:

1. Participants with no prior chemotherapy for advanced disease;
2. Participants who progress during or following a prior-platinum based chemotherapy regimen for advanced disease (2L+participants);
3. Participants who are 2L+ and previously treated for brain metastases.


Eligibility criteria: Inclusion Criteria:

* Stage IIIB (not eligible for definitive chemoradiotherapy), Stage IV, or recurrent NSCLC
* PDL1-positive status as determined by an immunohistochemistry assay performed by a central laboratory. A positive result in chemotherapy, chemoradiation of the tumor sample biopsy will satisfy the eligibility criterion
* Eastern Cooperative Oncology group Performance Status of 0 or 1
* Life expectancy greater than or equal to 12 weeks
* Measurable disease, as defined by Response Evaluation Criteria in Solid Tumors Version 1.1
* Adequate hematologic and end organ function

Exclusion Criteria:

* Any approved anti-cancer therapy, including chemotherapy, or hormonal therapy within 3 weeks prior to initiation of study treatment; the following exceptions are allowed. Hormone-replacement therapy or oral contraceptives, and tyrosine kinase inhibitors approved for treatment of NSCLC discontinued greater than 7 days prior to Cycle 1 Day 1
* Treatment with any other investigational agent or participation in another clinical trial with therapeutic intent within 28 days prior to enrollment
* Known central nervous system disease, including treated brain metastases in the following participants:

  1. who will not receive prior chemotherapy for advanced disease
  2. who progress during or following a prior-platinum based chemotherapy regimen for advanced disease (referred as 2L+ participants)
* Participants with a history of treated asymptomatic brain metastases are allowed in the 2L+ participants and previously treated for brain metastases.
* Leptomeningeal disease
* Uncontrolled tumor-related pain
* Uncontrolled hypercalcemia

Primary outcomes:
measure: Percentage of Participants With Objective Response According to Modified Response Evaluation Criteria in Solid Tumors (RECIST)
timeFrame: Baseline, and Day 1 of Cycle 1 (21-day cycle), then every 6 weeks for the first 12 months and then every 9 weeks thereafter until disease progression (up to 20 months)
Secondary outcomes:
measure: Percentage of Participants With Objective Response According to RECIST Version 1.1 (v1.1)
timeFrame: Baseline, and Day 1 of Cycle 1 (21-day cycle), then every 6 weeks for the first 12 months and then every 9 weeks thereafter until disease progression (up to 20 months)
measure: Duration of Objective Response According to RECIST v1.1
timeFrame: Baseline, and Day 1 of Cycle 1 (21-day cycle), then every 6 weeks for the first 12 months and then every 9 weeks thereafter until disease progression (up to 20 months)
measure: Percentage of Participants With 6-Month Duration of Objective Response
timeFrame: Month 6
measure: Percentage of Participants With Disease Progression or Death According to RECIST v1.1
timeFrame: Baseline to the first occurrence of progression or death, whichever occurs earlier (up to 20 months)
measure: Progression-Free Survival (PFS) According to RECIST v1.1
timeFrame: Baseline to the first occurrence of progression or death, whichever occurs earlier (up to 20 months)
measure: Percentage of Participants With PFS at Month 6, Month 12 and Month 30 According to RECIST v1.1
timeFrame: Months 6, 12 and 30
measure: Percentage of Participants With Disease Progression or Death According to Modified RECIST
timeFrame: Baseline to the first occurrence of progression or death, whichever occurs earlier (up to 20 months)
measure: PFS According to Modified RECIST
timeFrame: Baseline to the first occurrence of progression or death, whichever occurs earlier (up to 20 months)
measure: Percentage of Participants With PFS at Month 6, Month 12 and Month 30 According to Modified RECIST
timeFrame: Months 6, 12 and 30
measure: Percentage of Participants With Death
timeFrame: Baseline till death or up to 20 months, whichever occurred first
measure: Overall Survival (OS)
timeFrame: Baseline till death or up to 20 months, whichever occurred first
measure: Maximum Plasma Concentration (Cmax) for Atezolizumab
timeFrame: Pre-dose (0 hour) and 30 minutes after infusion on Day 1 of Cycle 1
measure: Minimum Plasma Concentration (Cmin) for Atezolizumab
timeFrame: Pre-dose (0 hour) on Day 1 of Cycles 2, 3, 4, 8, and 16
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: HonorHealth Research Institute - Pima Center
state: Arizona
city: Palo Alto
country: United States
facility: Stanford University/Lucile Packard Children's Hospital
state: California
city: Santa Monica
country: United States
facility: The Angeles Clinic and Research Institute, Santa Monica Office
state: California
city: Aurora
country: United States
facility: University Of Colorado
state: Colorado
city: New Haven
country: United States
facility: Yale University School Of Medicine
state: Connecticut
city: Washington
country: United States
facility: Georgetown University
state: District of Columbia
city: Orlando
country: United States
facility: Florida Hospital Cancer Inst
state: Florida
city: Port Saint Lucie
country: United States
facility: Hematology Oncology Associates of the Treasure Coast
state: Florida
city: Saint Petersburg
country: United States
facility: Florida Cancer Specialists.
state: Florida
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center and Research Inst.
state: Florida
city: Carrollton
country: United States
facility: Northwest Georgia Oncology Centers P.C.
state: Georgia
city: Chicago
country: United States
facility: The University of Chicago Medical Center
state: Illinois
city: Lebanon
country: United States
facility: Dartmouth Hitchcock Med Center; Norris Cotton Cancer Ctr
state: New Hampshire
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Durham
country: United States
facility: Duke University Health Systems
state: North Carolina
city: Huntersville
country: United States
facility: Carolina BioOncology Institute; Can Therapy & Res Ctr
state: North Carolina
city: Columbus
country: United States
facility: Ohio State Uni Hospital
state: Ohio
city: Hamilton
country: United States
facility: Oncology Hematology Care, Inc.
state: Ohio
city: Hershey
country: United States
facility: Penn State Univ. Milton S. Hershey Medical Center; MSHMC Cardiology
state: Pennsylvania
city: Philadelphia
country: United States
facility: Penn Presbyterian Medical Center; Abramson Cancer Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Nashville
country: United States
facility: SCRI-Tennessee Oncology
state: Tennessee
city: Salt Lake City
country: United States
facility: Huntsman Cancer Institute; University of Utah
state: Utah
city: Richmond
country: United States
facility: Virginia Cancer Institute
state: Virginia
city: Seattle
country: United States
facility: University of Washington Seattle Cancer Care Alliance
state: Washington
city: Wilrijk
country: Belgium
facility: Sint Augustinus Wilrijk
city: Lyon
country: France
facility: Centre Léon Bérard
city: Amsterdam
country: Netherlands
facility: Antoni van Leeuwenhoek Ziekenhuis
city: London
country: United Kingdom
facility: Queen Mary University of London
city: London
country: United Kingdom
facility: Royal Marsden Hospital - Fulham; Oncology Department
city: London
country: United Kingdom
facility: Royal Marsden Hospital - Fulham
Study officials:
affiliation: Genentech, Inc.
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Shemesh CS, Chan P, Legrand FA, Shames DS, Das Thakur M, Shi J, Bailey L, Vadhavkar S, He X, Zhang W, Bruno R. Pan-cancer population pharmacokinetics and exposure-safety and -efficacy analyses of atezolizumab in patients with high tumor mutational burden. Pharmacol Res Perspect. 2020 Dec;8(6):e00685. doi: 10.1002/prp2.685.