A Study of Atezolizumab as Neoadjuvant and Adjuvant Therapy in Resectable Non-Small Cell Lung Cancer (NSCLC) - Lung Cancer Mutation Consortium (LCMC3)
- Conditions
- Non-Small Cell Lung Cancer
- Interventions
- Registration Number
- NCT02927301
- Lead Sponsor
- Genentech, Inc.
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 181
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Atezolizumab Atezolizumab (MPDL3280A), an engineered anti-PD-L1 antibody Participants received two cycles of atezolizumab as neoadjuvant therapy prior to surgery. Participants who demonstrated clinical benefit were eligible to receive up to 12 months of atezolizumab.
- Primary Outcome Measures
Name Time Method Percentage of Participants With Major Pathologic Response (MPR) After surgery (approximately 10 weeks) Major pathologic response was defined as ≤10% of viable tumor cells as scored by a pathologist, based on surgical resection as defined by prior studies. Percentages have been rounded off to the nearest decimal point.
- Secondary Outcome Measures
Name Time Method 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 Pre-surgery (Day 36 +/- 3 days), after 2 doses of neoadjuvant treatment with atezolizumab ORR was defined as percentage of participants with complete response (CR) or partial response (PR) as determined by the investigator using RECIST v.1.1, assessed in the programmed death ligand 1 (PD-L1) positive (participants with combined tumor cell (TC)/ immune cell (IC) score categorized as TC1/2/3 or IC1/2/3) and PD-L1 negative (participants with TC/IC score was categorized as TC0 and IC0) groups. CR was defined as the disappearance of all target lesions or any pathological lymph nodes (whether target or non-target) having a reduction in short axis to \<10 millimeters (mm). PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. Percentages have been rounded off to the nearest decimal point.
Percentage of Participants With Major Pathologic Response for PD-L1-Positive Versus PD-L1-Negative Participants After surgery (approximately 10 weeks) Major pathologic response (MPR) was defined as ≤10% of viable tumor cells, as scored by a pathologist, based on surgical resection as defined by prior studies. MPR was assessed based on participants tumor cell (TC) and immune cell (IC) score. The participants were considered as PD-L1- positive if their combined TC/IC score was categorized as TC1/2/3 or IC1/2/3 and the participants were considered PD-L1 negative if TC/IC score was categorized as TC0 and IC0. Percentages have been rounded off to the nearest decimal point.
Number of Participants With at Least One Adverse Event From first study dose of atezolizumab until 90 days after the last study dose of atezolizumab (up to 18 months) An adverse event (AE) was defined as any untoward medical occurrence in participant administered a pharmaceutical product \& regardless of causal relationship with this treatment. An AE can therefore be any unfavorable \& unintended sign (including an abnormal laboratory finding), symptom/disease temporally associated with use of investigational product, whether or not considered related to investigational product. AEs were reported based on the National Cancer Institute Common Terminology Criteria for AEs, version 4.0 (NCI-CTCAE, v4.0).
Percentage of Participants With Major Pathologic Response (MPR) by Mutation Load Up to 13 weeks MPR was defined as ≤10% of viable tumor cells in the surgical resection as scored by a pathologist. Whole-exome sequencing (WES) was run, and the consequences of each mutation were determined using Ensembl Variant Effect Predictor (VEP). Mutation load (i.e. tumor mutation burden (TMB)) was defined as the number of variants altering protein sequence as outlined by VEP divided by 34 Megabase (MB) of assay target region. The final value was reported as number of mutations per megabase (mut/MB). It was divided into three groups: TMB \<10 mut/MB; TMB ≥ 10 mut/MB to \<16 mut/MB; and TMB ≥16 mut/MB. Percentages have been rounded off to the nearest decimal point.
Percentage of Participants With Major Pathologic Response (MPR) by Neoantigen Score Up to 13 weeks MPR was defined as ≤10% of viable tumor cells in the surgical resection as scored by a pathologist. MPR was analysed by neoantigen score, which was assessed based on the number of highly immunogenic, expressed neoantigens detected at baseline. Median splits were applied for analyses of MPR. Neoantigen scores \>/= 73 (i.e. \>/= 73 highly immunogenic, expressed neoantigens detected at baseline) were considered as high scores, and scores \<73 (i.e. \<73 highly immunogenic, expressed neoantigens detected at baseline) were considered as low neoantigen scores. Percentages have been rounded off to the nearest decimal point.
Percentage of Participants With Major Pathologic Response (MPR) by Gene Expression Signatures: Gene Set Variation Analysis (GSVA) Up to 13 weeks MPR was defined as ≤10% of viable tumor cells in the surgical resection as scored by a pathologist. MPR was analysed by gene set variation analysis (GSVA) scores. Bulk ribonucleic acid (RNA) from baseline tumor samples were assessed using GSVA for a T effector cell (Teff) signature comprising the following genes: cluster of differentiation 8A (CD8A), eomesodermin (EOMES), granzyme A (GZMA), T-box transcription factor 21 (TBX21), interferon-gamma (IFNG), granzyme B (GZMB), C-X-C motif chemokine ligand 9 (CXCL9), and C-X-C motif chemokine ligand 10 (CXCL10). Tertile splits were applied to GSVA scores, categorized as lower, middle, and upper scores, which indicated the relative levels of gene set expression in the baseline tumor samples. Percentages have been rounded off to the nearest decimal point.
Percentage of Participants With Major Pathologic Response (MPR) by Gene Expression Signatures: xCell Immune Score Up to 13 weeks MPR was defined as ≤10% of viable tumor cells in the surgical resection as scored by a pathologist. MPR was analysed by gene expression signatures. Bulk RNA from baseline tumor samples were assessed using xCell immune score. Tertile splits were applied to xCell immune scores, categorized as lower, middle, and upper scores, which indicated the relative levels of immune cell gene expression in the baseline tumor samples. Percentages have been rounded off to the nearest decimal point.
Trial Locations
- Locations (19)
City of Hope Comprehensive Cancer Center
🇺🇸Duarte, California, United States
UCLA Cancer Center
🇺🇸Santa Monica, California, United States
University Of Colorado
🇺🇸Aurora, Colorado, United States
Yale Cancer Center
🇺🇸New Haven, Connecticut, United States
Moffitt Cancer Center
🇺🇸Tampa, Florida, United States
Emory University; Winship Cancer Institute
🇺🇸Atlanta, Georgia, United States
Dana Farber Cancer Institute; Brigham and Womens Hospital
🇺🇸Boston, Massachusetts, United States
Mass General/North Shore Cancer
🇺🇸Danvers, Massachusetts, United States
Karmanos Cancer Inst; Hematology/Oncology
🇺🇸Detroit, Michigan, United States
Washington University; Wash Uni. Sch. Of Med
🇺🇸Saint Louis, Missouri, United States
Dartmouth Hitchcock Medical Center
🇺🇸Lebanon, New Hampshire, United States
Memorial Sloan Kettering - Monmouth
🇺🇸Middletown, New Jersey, United States
Memorial Sloan Kettering Cancer Center - Commack
🇺🇸Commack, New York, United States
Memorial Sloan Kettering Cancer Center at Westchester
🇺🇸Harrison, New York, United States
New York University Medical Center
🇺🇸New York, New York, United States
Memorial Sloan Kettering - Basking Ridge
🇺🇸New York, New York, United States
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
Memorial Sloan Kettering Nassau
🇺🇸Uniondale, New York, United States
The Ohio State University Comprehensive Cancer Center
🇺🇸Columbus, Ohio, United States