Clinical trial NCT02927301: A Study of Atezolizumab as Neoadjuvant and Adjuvant Therapy in Resectable Non-Small Cell Lung Cancer (NSCLC) - Lung Cancer Mutation Consortium (LCMC3)
Official title: A Phase II, Open-Label, Multicenter, Single-Arm Study to Investigate the Efficacy and Safety of Atezolizumab as Neoadjuvant and Adjuvant Therapy in Patients With Stage IB, II, IIIA, or Selected IIIB Resectable and Untreated 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: 2016-10-07
Enrollment: 181
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This study was designed to evaluate the safety and efficacy of neoadjuvant and adjuvant atezolizumab in participants with resectable Non-Small Cell Lung Cancer (NSCLC). Neoadjuvant therapy consisted of two 21-day cycles with atezolizumab. Following surgery, adjuvant therapy consisted of up to 12 months of atezolizumab in participants who demonstrate clinical benefit with neoadjuvant therapy. All participants who undergo surgery entered a surveillance period, which consisted of standardized blood sample collection and Chest CT Scans, for up to 2 years. All participants were monitored for disease recurrence and survival for up to 3 years after last dose of study drug.


Eligibility criteria: Inclusion Criteria:

* Pathologically documented Stage IB, II, IIIA, or selected IIIB, including T3N2 or T4 (by size criteria, not by mediastinal invasion) NSCLC
* Adequate pulmonary and cardiac function
* Available biopsy of primary tumor with adequate samples
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

Exclusion Criteria:

* NSCLC that is clinically T4 by virtue of mediastinal organ invasion or Stage IIIB by virtue of N3 disease
* Any prior therapy for lung cancer within 3 years.
* Prior treatment with anti-PD-1 or PD-L1 therapies
* History or risk of autoimmune disease

Primary outcomes:
measure: Percentage of Participants With Major Pathologic Response (MPR)
timeFrame: After surgery (approximately 10 weeks)
Secondary outcomes:
measure: Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) for PD-L1-Positive Versus PD-L1-Negative Participants
timeFrame: Pre-surgery (Day 36 +/- 3 days), after 2 doses of neoadjuvant treatment with atezolizumab
measure: Percentage of Participants With Major Pathologic Response for PD-L1-Positive Versus PD-L1-Negative Participants
timeFrame: After surgery (approximately 10 weeks)
measure: Number of Participants With at Least One Adverse Event
timeFrame: From first study dose of atezolizumab until 90 days after the last study dose of atezolizumab (up to 18 months)
measure: Percentage of Participants With Major Pathologic Response (MPR) by Mutation Load
timeFrame: Up to 13 weeks
measure: Percentage of Participants With Major Pathologic Response (MPR) by Neoantigen Score
timeFrame: Up to 13 weeks
measure: Percentage of Participants With Major Pathologic Response (MPR) by Gene Expression Signatures: Gene Set Variation Analysis (GSVA)
timeFrame: Up to 13 weeks
measure: Percentage of Participants With Major Pathologic Response (MPR) by Gene Expression Signatures: xCell Immune Score
timeFrame: Up to 13 weeks
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope Comprehensive Cancer Center
state: California
city: Santa Monica
country: United States
facility: UCLA Cancer Center
state: California
city: Aurora
country: United States
facility: University Of Colorado
state: Colorado
city: New Haven
country: United States
facility: Yale Cancer Center
state: Connecticut
city: Tampa
country: United States
facility: Moffitt Cancer Center
state: Florida
city: Atlanta
country: United States
facility: Emory University; Winship Cancer Institute
state: Georgia
city: Boston
country: United States
facility: Dana Farber Cancer Institute; Brigham and Womens Hospital
state: Massachusetts
city: Danvers
country: United States
facility: Mass General/North Shore Cancer
state: Massachusetts
city: Detroit
country: United States
facility: Karmanos Cancer Inst; Hematology/Oncology
state: Michigan
city: Saint Louis
country: United States
facility: Washington University; Wash Uni. Sch. Of Med
state: Missouri
city: Lebanon
country: United States
facility: Dartmouth Hitchcock Medical Center
state: New Hampshire
city: Middletown
country: United States
facility: Memorial Sloan Kettering - Monmouth
state: New Jersey
city: Commack
country: United States
facility: Memorial Sloan Kettering Cancer Center - Commack
state: New York
city: Harrison
country: United States
facility: Memorial Sloan Kettering Cancer Center at Westchester
state: New York
city: New York
country: United States
facility: New York University Medical Center
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering - Basking Ridge
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Uniondale
country: United States
facility: Memorial Sloan Kettering Nassau
state: New York
city: Columbus
country: United States
facility: The Ohio State University Comprehensive Cancer Center
state: Ohio
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Chaft JE, Oezkan F, Kris MG, Bunn PA, Wistuba II, Kwiatkowski DJ, Owen DH, Tang Y, Johnson BE, Lee JM, Lozanski G, Pietrzak M, Seweryn M, Byun WY, Schulze K, Nicholas A, Johnson A, Grindheim J, Hilz S, Shames DS, Rivard C, Toloza E, Haura EB, McNamee CJ, Patterson GA, Waqar SN, Rusch VW, Carbone DP; LCMC study investigators. Neoadjuvant atezolizumab for resectable non-small cell lung cancer: an open-label, single-arm phase II trial. Nat Med. 2022 Oct;28(10):2155-2161. doi: 10.1038/s41591-022-01962-5. Epub 2022 Sep 12.