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]

Non-Small Cell Lung Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01846416
• Other study ID #: GO28625
• Secondary ID: 2013-000177-69
• Status: Completed
• Phase: Phase 2
• Start date: May 30, 2013
• Est. completion date: December 18, 2017

Study information

• Verified date: December 2018
• Source: Genentech, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 138
• Est. completion date: December 18, 2017
• Est. primary completion date: January 7, 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non-Small Cell Lung Cancer

Intervention

Drug:
• Atezolizumab (MPDL3280A) [TECENTRIQ], an engineered anti-PDL1 antibody
Atezolizumab 1200 mg IV on Day 1 of each 21-day cycle until disease progression.

Locations

Country	Name	City	State
Belgium	Sint Augustinus Wilrijk	Wilrijk
France	Centre Léon Bérard	Lyon
Netherlands	Antoni van Leeuwenhoek Ziekenhuis	Amsterdam
United Kingdom	Queen Mary University of London	London
United Kingdom	Royal Marsden Hospital - Fulham	London
United Kingdom	Royal Marsden Hospital - Fulham; Oncology Department	London
United States	University Of Colorado	Aurora	Colorado
United States	Northwest Georgia Oncology Centers P.C.	Carrollton	Georgia
United States	The University of Chicago Medical Center	Chicago	Illinois
United States	Ohio State Uni Hospital	Columbus	Ohio
United States	Duke University Health Systems	Durham	North Carolina
United States	Oncology Hematology Care, Inc.	Hamilton	Ohio
United States	Penn State Univ. Milton S. Hershey Medical Center; MSHMC Cardiology	Hershey	Pennsylvania
United States	Carolina BioOncology Institute; Can Therapy & Res Ctr	Huntersville	North Carolina
United States	Dartmouth Hitchcock Med Center; Norris Cotton Cancer Ctr	Lebanon	New Hampshire
United States	SCRI-Tennessee Oncology	Nashville	Tennessee
United States	Yale University School Of Medicine	New Haven	Connecticut
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Florida Hospital Cancer Inst	Orlando	Florida
United States	Stanford University/Lucile Packard Children's Hospital	Palo Alto	California
United States	Penn Presbyterian Medical Center; Abramson Cancer Center	Philadelphia	Pennsylvania
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	Hematology Oncology Associates of the Treasure Coast	Port Saint Lucie	Florida
United States	Virginia Cancer Institute	Richmond	Virginia
United States	Florida Cancer Specialists.	Saint Petersburg	Florida
United States	Huntsman Cancer Institute; University of Utah	Salt Lake City	Utah
United States	The Angeles Clinic and Research Institute, Santa Monica Office	Santa Monica	California
United States	HonorHealth Research Institute - Pima Center	Scottsdale	Arizona
United States	University of Washington Seattle Cancer Care Alliance	Seattle	Washington
United States	H. Lee Moffitt Cancer Center and Research Inst.	Tampa	Florida
United States	Georgetown University	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Genentech, Inc.

Countries where clinical trial is conducted

United States,  Belgium,  France,  Netherlands,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants With Objective Response According to Modified Response Evaluation Criteria in Solid Tumors (RECIST)	Objective response was defined as a complete response (CR) or partial response (PR), as determined by investigator according to modified RECIST criteria. Modified RECIST was derived from RECIST v1.1 conventions and immune related response criteria. CR was defined as disappearance of all tumor lesions (target lesion [TL] and non-target lesion [non-TL]) and no new measurable or unmeasurable lesions, all lymph node short axes must be less than 10 millimeters (mm), and PR was defined as at least 30 percent (%) decrease in sum of diameter of TLs and all new measurable lesions since baseline in absence of CR, and both confirmed by consecutive assessment greater than or equal to 4 weeks from date first documented. Participants not meeting these criteria, including participants without at least one post-baseline response assessment were considered as non-responders.	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	Percentage of Participants With Objective Response According to RECIST Version 1.1 (v1.1)	Objective response was defined as a CR or PR, as determined by the investigator according to RECIST v1.1. For TLs, CR was defined as disappearance of all TLs. Any pathological lymph nodes, whether target or non-target, must had reduction in short axis to less than 10 mm. PR was defined as at least a 30% decrease in the sum of diameter of TLs, taking as reference the baseline sum of diameters, in absence of CR. For non-TLs, CR was defined as disappearance of all non-TLs and if applicable, normalization of tumor marker level. Participants not meeting these criteria, including participants without at least 1 post-baseline response assessment were considered as non-responders.	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	Duration of Objective Response According to RECIST v1.1	Duration of objective response was defined as time from initial occurrence of documented CR or PR until documented disease progression (using RECIST v1.1 as determined by investigator) or death, whichever occurred first. For TLs, CR was defined as disappearance of all TLs. Any pathological lymph nodes, whether target or non-target, must had reduction in short axis to less than 10 mm. PR was defined as at least a 30% decrease in sum of diameter of TLs, taking as reference baseline sum of diameters, in absence of CR. Progressive disease was at least a 20% increase in sum of diameters of TLs, taking as reference smallest sum on study (nadir). For non-TLs, CR was defined as disappearance of all non-TLs and if applicable, normalization of tumor marker level. Progressive disease was defined as the appearance of 1 or more new lesions and/or unequivocal progression of existing non-TLs. Participants were censored at the date of last tumor assessment.	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	Percentage of Participants With 6-Month Duration of Objective Response	Duration of objective response at 6 months was defined as time from initial occurrence of documented CR or PR until Month 6. For TLs, CR was defined as disappearance of all TLs. Any pathological lymph nodes, whether target or non-target, must have reduction in short axis to less than 10 mm. PR was defined as at least a 30% decrease in sum of diameter of TLs, taking as reference baseline sum of diameters, in absence of CR. For non-TLs, CR was defined as disappearance of all non-TLs and if applicable, normalization of tumor marker level. Participants were censored at the date of last tumor assessment.	Month 6
Secondary	Percentage of Participants With Disease Progression or Death According to RECIST v1.1	For TLs, progressive disease was defined as at least a 20% increase in the sum of diameters of TLs, taking as reference the smallest sum on study (nadir). For non-TLs, progressive disease was defined as the appearance of 1 or more new lesions and/or unequivocal progression of existing non-TLs.	Baseline to the first occurrence of progression or death, whichever occurs earlier (up to 20 months)
Secondary	Progression-Free Survival (PFS) According to RECIST v1.1	PFS was defined as time from randomization to first occurrence of documented disease progression (based on RECIST v1.1 criteria) or death due to any cause within 30 days of the last treatment, whichever occurs earlier as determined by investigator. For TLs, progressive disease was defined as at least a 20% increase in the sum of diameter of TLs, taking as reference the smallest sum on study (nadir). For non-TLs, progressive disease was defined as the appearance of 1 or more new lesions and/or unequivocal progression of existing non-TLs. In event of no disease progression or documented death, PFS was censored at date of last evaluable tumor assessment. Participants with no post-baseline tumor assessments were censored at the time of first dose plus 1 day.	Baseline to the first occurrence of progression or death, whichever occurs earlier (up to 20 months)
Secondary	Percentage of Participants With PFS at Month 6, Month 12 and Month 30 According to RECIST v1.1	Percentage of participants who were progression free at Month 6 and 12 (based on RECIST v1.1) was reported. For TLs, progressive disease was defined as at least a 20% increase in the sum of diameter of TLs, taking as reference the smallest sum on study (nadir). For non-TLs, progressive disease was defined as the appearance of 1 or more new lesions and/or unequivocal progression of existing non-TLs.	Months 6, 12 and 30
Secondary	Percentage of Participants With Disease Progression or Death According to Modified RECIST	For TLs, progressive disease was defined as at least a 20% increase in the sum of diameters of TLs and new measurable lesions, taking as reference the smallest sum recorded since treatment started.	Baseline to the first occurrence of progression or death, whichever occurs earlier (up to 20 months)
Secondary	PFS According to Modified RECIST	PFS according to modified RECIST was defined as time from first dose of atezolizumab to first occurrence of documented disease progression or death due to any cause, as determined by investigator for participants who discontinued at first documented radiographic progression. For participants who continued beyond first documented progression and had follow-up tumor assessment or death, PFS was defined as time from first dose of atezolizumab to subsequent radiographic progression or death. For TLs, progressive disease was defined as at least a 20% increase in the sum of diameters of TLs and new measurable lesions, taking as reference the smallest sum recorded since treatment started. In event of no disease progression or documented death, PFS was censored at date of last evaluable tumor assessment.	Baseline to the first occurrence of progression or death, whichever occurs earlier (up to 20 months)
Secondary	Percentage of Participants With PFS at Month 6, Month 12 and Month 30 According to Modified RECIST	Percentage of participants who were progression free at Months 6 and 12 (according to modified RECIST). For TLs, progressive disease was defined as at least a 20% increase in the sum of diameters of TLs and new measurable lesions, taking as reference the smallest sum recorded since treatment started.	Months 6, 12 and 30
Secondary	Percentage of Participants With Death	Participants were followed for survival throughout the study.	Baseline till death or up to 20 months, whichever occurred first
Secondary	Overall Survival (OS)	OS was defined as the time from first dose of the study drug to the time of death from any cause of the study. Participants who were still alive at the time of analysis were censored at the time of their last study assessment (for active participants) or at the last date known alive (for participants in follow-up). If no post-baseline data were available, OS was censored at the date of first treatment plus 1 day.	Baseline till death or up to 20 months, whichever occurred first
Secondary	Maximum Plasma Concentration (Cmax) for Atezolizumab		Pre-dose (0 hour) and 30 minutes after infusion on Day 1 of Cycle 1
Secondary	Minimum Plasma Concentration (Cmin) for Atezolizumab		Pre-dose (0 hour) on Day 1 of Cycles 2, 3, 4, 8, and 16