The Cancer Research Institute and The Mark Foundation for Cancer Research have launched an innovative clinical trial that aims to demonstrate the utility of liquid biopsy in assessing responses of patients with lung cancer to immunotherapy (ClinicalTrials.gov identifier NCT04093167). If the trial and future studies show that this approach can more accurately characterize responses to therapy, oncologists may gain a more reliable, less costly, and less invasive means to help them to identify earlier the potential effectiveness of immunotherapy as opposed to other therapeutic options.
The phase II, multicenter trial will be conducted by the Canadian Cancer Trials Group, with clinical investigators at five sites in Canada and at John Hopkins University in the United States. Valsamo Anagnostou, MD, PhD, Assistant Professor of Oncology, Director of the Thoracic Oncology Biorepository, and an investigator for the Swim Across America Lab at the Johns Hopkins Kimmel Comprehensive Cancer Center, is the study’s Chair.
Valsamo Anagnostou, MD, PhD
In the trial’s first stage, investigators will explore whether distinct dynamic changes in the levels of circulating cell-free tumor DNA (ctDNA) associated with patterns of clinical response or resistance to immunotherapy are superior to radiographic response assessments. Liquid biopsies from patients in the trial will be analyzed by Personal Genome Diagnostics. In the trial’s second stage, investigators will prospectively examine whether these patterns can effectively guide treatment decisions for patients with non–small cell lung cancer. In the second stage of the study, ctDNA analysis will be used to determine whether a patient should receive immunotherapy alone or in combination with chemotherapy.
Building on a Groundbreaking Study
Evidence of ctDNA as a clinically relevant dynamic biomarker for assessment and prediction of responses to immunotherapy was first demonstrated in a groundbreaking paper published in Cancer Research.1 Dr. Anagnostou and colleagues showed that posttreatment changes in ctDNA levels reliably predicted later clinical responses.
Specifically, Dr. Anagnostou and her team reported that patients whose ctDNA levels fell after receiving immunotherapy had better clinical responses, whereas patients whose ctDNA levels remained unchanged or increased responded poorly or not at all. Of note, ctDNA measurement allowed for a more accurate prediction of patient responses of up to 8.7 weeks earlier on average than is possible with conventional computerized tomography imaging.
1. Anagnostou V, Forde PM, White JR, et al: Dynamics of tumor and immune responses during immune checkpoint blockade in non–small cell lung cancer. Cancer Res 79:1214-1225, 2019.