Validation of a tissue-based predictive RNA test for immunotherapy benefit in NSCLC: the PREDAPT study.

Lung cancer remains the leading cause of cancer mortality worldwide. Immune checkpoint inhibitors (ICI) targeting PD-1/PD-L1 have significantly improved outcomes in a subset of patients. OncoPrism, a clinical test employing a multidimensional predictive RNA-based immune biomarker, was evaluated for predicting immune checkpoint inhibitor benefit in non-small cell lung cancer (NSCLC) patients. This study evaluated OncoPrism in 1487 patients across four NSCLC cohorts: one PD-L1 inhibitor cohort (n = 195), one PD-1 inhibitor cohort (n = 89), and two non-ICI cohorts (n = 193 and n = 1010). In the PD-L1 inhibitor cohort, OncoPrism predicted progression-free survival (p < 0.0001) and overall survival (p = 0.043). In the PD-1 inhibitor cohort, an observational clinical trial, PREDAPT, enrolling patients from 17 healthcare systems, OncoPrism predicted overall response rate (p = 0.008), progression-free survival (p = 0.004), and overall survival (p = 0.011). PD-L1 Tumor Proportion Score (TPS) was not predictive of response, progression-free survival, or overall survival. OncoPrism did not predict overall survival across two non-ICI NSCLC cohorts (p = 0.54, p = 0.73), suggesting the test is specifically predictive of ICI benefit rather than being prognostic with more limited clinical utility. Overall, the data show OncoPrism high patients have two to three-fold greater overall response rate, progression-free survival, and overall survival compared to those in other OncoPrism groups. These results underscore the impact of OncoPrism to address the current unmet need for ICI response prediction in NSCLC. This trial was registered with ClinicalTrials.gov, number NCT04510129, on 10 August 2020.