Clinical validation of Guardant360 CDx as a blood-based companion diagnostic for sotorasib. (April 2022)

• Record Type: Journal Article
• Authors: Bauml, Joshua M.; Li, Bob T.; Velcheti, Vamsidhar; Govindan, Ramaswamy; Curioni-Fontecedro, Alessandra; Dooms, Christophe; Takahashi, Toshiaki; Duda, Andrew W.; Odegaard, Justin I.; Cruz-Guilloty, Fernando; Jin, Liming; Zhang, Ying; Anderson, Abraham; Skoulidis, Ferdinandos
• Is Part Of: Lung cancer. Volume 166(2022)
• Page Start: 270
• Page End: 278
• Publication Date: 2022-04
• Subjects: Sotorasib -- Liquid biopsy -- Carcinoma, non–small-cell lung -- Biomarkers -- Tumor -- Molecular diagnostic techniques; AAAS assay agreement analysis set -- ALK anaplastic lymphoma kinase -- CDx companion diagnostics -- CI confidence interval -- cfDNA cell-free DNA -- ctDNA circulating tumor DNA -- CR complete response -- DCR disease control rate -- DOR duration of response -- ECOG Eastern Cooperative Oncology Group -- EGFR epidermal growth factor receptor -- FDA US Food and Drug Administration -- G360 Guardant360 -- GCLP Good Clinical Laboratory Practice -- GTP guanosine-5′-triphosphate -- IQR interquartile range -- KRAS Kirsten rat sarcoma -- LBx liquid biopsy -- NGS next-generation sequencing -- NPA negative percentage agreement -- NSCLC non–small-cell lung cancer -- ORR objective response rate -- PCR polymerase chain reaction -- PD progressive disease -- PD-1 programmed cell death protein-1 -- PD-L1 programmed cell death protein ligand-1 -- PPA positive percentage agreement -- PR partial response -- QC quality control -- RECIST Response Evaluation Criteria in Solid Tumors -- RGQ Rotor-Gene-Q MDx instrument -- ROS1 receptor tyrosine kinase -- SAAS sensitivity analysis prevalence sub-study -- SD stable disease -- SMM sum of mutant molecules -- TAT turnaround time -- TTR time to response; Lungs -- Cancer -- Periodicals; Lung Neoplasms -- Abstracts; Lung Neoplasms -- Periodicals; Poumons -- Cancer -- Périodiques; Lungs -- Cancer; Periodicals; Electronic journals; Electronic journals; 616.99424
• DOI: 10.1016/j.lungcan.2021.10.007
• Languages: English
• ISSNs: 0169-5002

Abstract

Highlights: Insufficient genotyping remains common in non–small-cell lung cancer (NSCLC). Comprehensive genotyping is critical for proper management of NSCLC patients. Guardant360 CDx is a next-generation sequencing–based liquid biopsy test. Guardant360 CDx has clinical validity in identifying KRAS p.G12C–mutant NSCLC. Guardant 360 CDx may be a useful tool for determining eligibility of sotorasib therapy. Abstract: Objectives: Effective therapy for non–small-cell lung cancer (NSCLC) depends on morphological and genomic classification, with comprehensive screening for guideline-recommended biomarkers critical to guide treatment. Companion diagnostics, which provide robust genotyping results, represent an important component of personalized oncology. We evaluated the clinical validity of Guardant360 CDx as a companion diagnostic for sotorasib for detection of KRAS p.G12C, an important oncogenic NSCLC driver mutation. Materials and Methods: KRAS p.G12C was tested in NSCLC patients from CodeBreaK100 (NCT03600833) in pretreatment plasma samples using Guardant360 CDx liquid biopsy and archival tissue samples using therascreen® KRAS RGQ polymerase chain reaction (PCR) kit tissue testing. Matched tissue and plasma samples were procured from other clinical trials or commercial vendors, and results were compared. Demographics and clinical characteristics and objective response rate (ORR) were evaluated. Results: Of 126 CodeBreaK patients, 112 (88.9%) were tested for KRAS p.G12C mutations with Guardant360 CDx. Among 189 patients in the extended analysis cohort, the positive and negative percent agreement (95% CI) for Guardant360 CDx plasma testing relative to therascreen® KRAS RGQ PCR kit tissue testing were 0.71 (0.62, 0.79) and 1.00 (0.95, 1.00), respectively; overall percent agreement (95% CI) was 0.82 (0.76, 0.87). TP53 co-mutations were the most common regardless of KRAS p.G12C status ( KRAS p.G12C–positive, 53.4%; KRAS p.G12C–negative, 45.5%). STK11 was co-mutated in 26.1% of KRAS p.G12C–positive samples. The ORR was similar among patients selected by plasma and tissue testing. Conclusion: Comprehensive genotyping for all therapeutic targets including KRAS p.G12C is critical for management of NSCLC. Liquid biopsy using Guardant360 CDx has clinical validity for identification of patients with KRAS p.G12C–mutant NSCLC and, augmented by tissue testing methodologies as outlined on the approved product label, will identify patients for treatment with sotorasib.