The vast majority of patients with stage I (tumors ≥ 4cm), IIA, IIB (and select stage III) NSCLC are managed with upfront surgery, followed by adjuvant chemotherapy. However, relapse rates remain high and are primarily due to distant, metastatic disease. Previous meta-analysis evaluating the use of neo-adjuvant chemotherapy and adjuvant chemotherapy demonstrate a similar impact on improved disease free survival (DFS) and overall survival (OS). The role of checkpoint inhibitors has been proven to be effective in the treatment of patients with advanced NSCLC, regardless of histology and PD-L1 expression. Results from trials evaluating the use of checkpoint inhibitors alone or in combination with chemotherapy in the neoadjuvant setting for early stage disease are promising. However, there are no trials evaluating the role of concomitant chemotherapy and checkpoint inhibitors in the adjuvant setting. In addition, emerging data supports the use of ctDNA as a promising biomarker for early detection of minimal residual disease and have indicated that the presence of detectable ctDNA after surgery for localized lung cancer is correlated with a 90-100% chance for disease recurrence. Therefore, we propose this current study assessing concomitant chemotherapy plus Atezolizumab in the adjuvant setting for patients with stage I (tumors ≥ 4cm), IIA, IIB (and select stage III) NSCLC who have detectable ctDNA after surgery. The clearance of ctDNA will serve as a surrogate for long term DFS and OS in this patient population.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
100
Atezolizumab 1200 mg
Docetaxel 60-75 mg/m\^2
60-75 mg/m\^2
Pemetrexed 500mg/m\^2
Northwestern University Feinberg School of Medicine
Chicago, Illinois, United States
Indiana University Melvin and Bren Simon Cancer Center
Indianapolis, Indiana, United States
Summit Health
Berkeley Heights, New Jersey, United States
Rutgers Cancer Institute of New Jersey
New Brunswick, New Jersey, United States
New York University Clinical Cancer Center
New York, New York, United States
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, United States
Penn State Cancer Institute
Hershey, Pennsylvania, United States
University of Virginia Health System
Charlottesville, Virginia, United States
University of Wisconsin
Madison, Wisconsin, United States
Percentage of patients with undetectable ctDNA after 4 cycles of adjuvant chemotherapy + Atezolizumab plus up to 13 additional cycles of Atezolizumab in patients with stage I (tumors ≥ 4cm), IIA, IIB, and select stage III [any T1-3 N1-2 and T4N0-2]
To estimate the percentage of patients with undetectable circulating tumor DNA (ctDNA) after 4 cycles of adjuvant chemotherapy + Atezolizumab plus up to 13 additional cycles of Atezolizumab in patients with stage I (tumors ≥ 4cm), IIA, IIB, and select stage III \[any T1-3 N1-2 and T4N0-2\] NSCLC who have detectable ctDNA after surgery, but prior to adjuvant therapy. At each time point, ctDNA detection status (detectable or not detectable) will be determined by CAPP-seq using the Monte Carlo-based ctDNA detection index cutoff point of \< 0.05, as described by Newman et al \[53, 54\]. If ctDNA detection index is \> 0.05, ctDNA will be classified as not detected at that time point, whereas if \< 0.05 then it will be classified as detected.
Time frame: Up to 17 cycles (13 months)
Percentage of patients with clearance of ctDNA after 4 cycles of adjuvant chemotherapy + Atezolizumab
To estimate the percentage of patients with clearance of ctDNA after 4 cycles of adjuvant chemotherapy + Atezolizumab in patients with stage I (tumors ≥ 4 cm), IIA, IIB, and select stage III \[any T1-3 N1-2 and T4N0-2\] NSCLC who have undergone surgical resection with detectable ctDNA after surgery.
Time frame: 4 cycles (3 months)
Percentage of patients with clearance of ctDNA after 8 cycles (4 cycles of adjuvant chemotherapy + Atezolizumab plus 4 additional cycles of Atezolizumab)
To estimate the percentage of patients with clearance of ctDNA after 8 cycles (4 cycles of adjuvant chemotherapy + Atezolizumab plus 4 additional cycles of Atezolizumab) in patients with stage I (tumors ≥ 4 cm), IIA, IIB, and select stage III \[any T1-3 N1-2 and T4N0-2\] NSCLC who have undergone surgical resection with detectable ctDNA after surgery.
Time frame: 8 cycles (6 months)
Percentage of patients with clearance of ctDNA after 12 cycles (4 cycles of adjuvant chemotherapy + Atezolizumab plus 8 additional cycles of Atezolizumab)
To estimate the percentage of patients with clearance of ctDNA after 12 cycles (4 cycles of adjuvant chemotherapy + Atezolizumab plus 8 additional cycles of Atezolizumab) in patients with stage I (tumors ≥ 4 cm), IIA, IIB, and select stage III \[any T1-3 N1-2 and T4N0-2\] NSCLC who have undergone surgical resection with detectable ctDNA after surgery.
Time frame: 12 cycles (9 months)
Percentage of patients with clearance of ctDNA during or after adjuvant chemotherapy + Atezolizumab followed by Atezolizumab for up to 13 additional cycles who had no detectable ctDNA after surgery
To estimate the percentage of patients with clearance of ctDNA during or after adjuvant chemotherapy + Atezolizumab followed by Atezolizumab for up to 13 additional cycles who had no detectable ctDNA after surgery
Time frame: Up to 17 cycles (13 months)
Percentage of pts with clearance of ctDNA after 4 cycles of adj. chemotherapy + Atezolizumab plus up to 13 additional cycles of Atezolizumab
To estimate the percentage of patients with undetectable ctDNA after 4 cycles of adjuvant chemotherapy + Atezolizumab plus up to 13 additional cycles of Atezolizumab in patients with stage I (tumors ≥ 4 cm), IIA, IIB, and select stage III \[any T1-3 N1-2 and T4N0-2\] NSCLC who have undergone surgical resection, regardless of ctDNA status after surgery
Time frame: Up to 17 cycles (13 months)
1 year Disease Free Survival (DFS) in all patients
To estimate the 1 year Disease Free Survival (DFS) in all patients treated on study
Time frame: 1 year
1 year Disease Free Survival (DFS) in patients with no detectable ctDNA after 4 cycles of adjuvant chemotherapy + Atezolizumab who had detectable ctDNA after surgery.
To estimate the 1 year Disease Free Survival (DFS) in patients with no detectable ctDNA after 4 cycles of adjuvant chemotherapy + Atezolizumab who had detectable ctDNA after surgery.
Time frame: 1 year
1 year Disease Free Survival (DFS) in patients with detectable ctDNA after 1 year of adjuvant therapy on study
1 year Disease Free Survival (DFS) in patients with detectable ctDNA after 1 year of adjuvant therapy on study
Time frame: 1 year
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