A new study published in the Nature Press publication Communications Medicine validates the clinical utility of a pan-solid tumor biomarker, IRS (Immunotherapy Response Score), that predicts the benefit of anti-PD-1/PD-L1 checkpoint inhibitor monotherapy (“Development and validation of an integrative pan-solid tumor predictor of PD-1/PD-L1 blockade benefit”).
IRS was developed and validated by Strata Oncology, a next-generation precision oncology company, using treatment data and comprehensive, clinically validated genomic and transcriptomic profiling of tumor tissue from the observational Strata Trial (NCT03061305), an ongoing clinical trial evaluating the impact of molecular profiling for patients with advanced solid tumors.
The IRS algorithm, developed using Cox modeling and validated in an independent cohort of trial patients, captures the biology of the tumor and its microenvironment by combining TMB (tumor mutation burden) analysis with the quantitative expression of CD274, PDCD1, ADAM12, and TOP2A to predict pembrolizumab rwPFS (real-world progression-free survival).
“Our Immunotherapy Response Score [IRS] meets a significant unmet medical need for an integrative diagnostic test that better predicts likelihood of benefit from anti-PD-1/PD-L1 checkpoint inhibitor monotherapy, across solid tumor types,” said Scott Tomlins, MD, PhD, Strata Oncology co-founder and chief medical officer. “Current pan-tumor biomarkers for these treatments identify only a fraction of responsive patients, meaning far too many people who could benefit from these therapies are not being identified.”
Tomlins added, “Additionally, immunotherapy is now often combined with chemotherapy. Our exploratory data in non-small cell lung cancer indicate that IRS may be a useful tool to help determine which patients can achieve similar benefits without the toxic effects of chemotherapy.”
Checkpoint inhibitors such as anti-PD-1/PD-L1 checkpoint inhibitors, activate the immune system and have been successfully used to treat patients with advanced cancers. However, not all cancer patients benefit from these wonder drugs and many patients rapidly develop resistance to them. Therefore, the development of biomarkers and molecular tests that identify patients who would benefit from checkpoint inhibitors is important.
Based on data collected from over 20,000 patients with more than 20 types of advanced cancers, the investigators demonstrated that IRS can better predict the benefit of anti-PD-1/PD-L1 checkpoint inhibitor therapy than tests that are in current use. IRS identified nearly 8% of patients with advanced cancer who may benefit from checkpoint inhibitors but would not receive them at present based on current molecular tests, thereby offering clinicians a better decision-making tool to stratify patients who should receive checkpoint inhibitor therapy.
IRS predicted rwPFS and overall survival (OS) in anti-PD-1/PD-L1 monotherapy-treated patients across tumor types. A high IRS predicted a similar duration of benefit as high TMB across tumor types, but IRS identified twice as many patients who may benefit from checkpoint inhibitor treatment as TMB. Moreover, patients with non-small cell lung cancer (NSCLC) patients and a high IRS status showed no significant benefit of combination therapy (pembrolizumab + chemotherapy) compared to monotherapy (pembrolizumab).
“Immunotherapy has transformed cancer care and now with IRS we have the ability to predict benefit across tumor types,” said Dan Rhodes, PhD, Strata Oncology co-founder and CEO. “We are excited to put this novel biomarker into the hands of physicians to help them ensure every patient gets their best possible therapy.”