Predictors of immunotherapeutic benefits in patients with advanced melanoma and other malignancies treated with immune checkpoint inhibitors utilizing ORIEN “real-world” data.

2618 Background: Despite the significant improvements in treating cancer with immune checkpoint inhibitors (ICIs), many patients (pts) do not achieve disease control. Using Oncology Research Information Exchange Network (ORIEN) Avatar real-world data conducted under the Total Cancer Care protocol we investigate predictive biomarkers of ICI benefits in pts with advanced malignancies. Methods: Clinical data were normalized as part of ORIEN Avatar. RNA-seq was performed on tumor samples following the RSEM pipeline and gene expressions were quantified as Transcript Per Million (TPM). Gene expressions (GE) were log2(TPM+1) transformed. Mann-Whitney U-test was used to compute differences between groups, and Kaplan-Meier survival analysis was performed. Results: Pts (n=1214) with 27 cancer types treated with ICIs were retrieved from the database, where 1143 and 875 patients were profiled by WES and RNA-seq, respectively. 804 pts had both WES and RNA-seq data. The top six cancer types were renal cell carcinoma (n=206), non-small cell lung cancer (n=173), head and neck cancer (n=157), melanoma (n=154), sarcomas (n=99) and bladder cancer (n=87). The ICI regimens included therapy with atezolizumab (n=87), avelumab (n=12), cemiplimab (n=6), ipilimumab (n=47), nivolumab (n=424), pembrolizumab (n=525) and ipilimumab+nivolumab (n=113). Median overall survival (OS) for the entire cohort was 21.9 months. Patients had significant improvement in OS if ICI was given in the first line ( P<0.0001). Previously published GE signatures were tested in the melanoma cohort. Signatures related to IFNg, effector T cells, chemokines, MHC II and Tertiary Lymphoid Structures were significantly prognostic and predictive of ICI benefits in advanced melanoma (Table). Analyses in the other cancer types are ongoing. Conclusions: GE data analyses validate the predictive value of immune related gene signatures following ICI immunotherapy in melanoma. Ongoing analyses are investigating these signatures in other malignancies and integrating the GE data with data related to TMB, somatic mutations and germline genetic variations.[Table: see text]