Tyler Nielsen, MBioMed, Staff Scientist at Oncocyte Corporation. In this video, he speaks about the AACR 22 Abstract – 1272 / 19 – Confirmatory study of the IO Score, a tumor immune microenvironment (TIME) classifier, demonstrates efficacy in a real-world cohort of metastatic urothelial cancer (mUC) patients treated with immune checkpoint inhibitors (ICIs).
Outline
Origins:
Patients with mUC have a terrible prognosis, with less than 10% surviving two years following diagnosis. Because the majority of mUC patients do not survive to a second line of therapy, optimizing first-line therapy is crucial, particularly with recently approved non-ICI therapies. The IO Score, a 27-gene TIME classifier, has previously been linked to ICI response in mUC (IMvigor210; n= 348), NSCLC, renal cancer, and a randomized TNBC study (NeoTRIPaPDL1; n= 258).
Clinical effect was seen in less than 30% of patients in a real-world investigation of ICI therapy in mUC patients (UNC-108) (Rose, 2021). In this cohort, the IO Score was assessed for ICI efficacy to validate findings from IMvigor210, where the IO Score was both independent and complimentary to TMB.
Strategies:
The previously described IO score system was used to available RNAseq data from the UNC-108 study’s 77 subjects. The IO Score, TMB, and TMB and/or IO Score positivity were determined using a six-week front censor for OS, Cox proportional hazards for OS, and PFS, as well as a six-week front censor for OS, Cox proportional hazards for OS, and PFS. Both the ORR and OR were calculated using responses (CR/PR/SD for more than 6 months). There was no PD-L1 staining available.
Observations:
These findings support the IO Score’s connection with ICI response in a second, independent mUC cohort using the same procedure and threshold previously established and confirmed in other tumor types. The IO Score identified more responses than TMB alone and gave independent biomarker value. The IO Score gives unique information on both the inflammatory and cancer-associated fibroblast biologic signatures of ICI response, and it can be supplemented by other ICI-associated biomarkers. As a result, this tool has the potential to inform therapy decisions and enhance the outcomes of mUC patients.