ctDNA Test Improves Early Detection of Immunotherapy Response in Cancer

Findings of a recent study have demonstrated the efficacy of a blood-only circulating tumor DNA (ctDNA) test in monitoring the response to pembrolizumab (Keytruda), in patients with metastatic solid tumors. This addresses a significant challenge in oncology: the timely detection of tumor response, which is critical for managing resistant cases effectively.^1,2

The study, which is part of the phase 2 INSPIRE trial (NCT02644369), employed a tissue-agnostic genome-wide methylation enrichment assay known as cell-free methylated DNA immunoprecipitation combined with high-throughput sequencing (cfMeDIP-seq). This innovative approach allows for the assessment of tumor dynamics through blood samples, eliminating the need for matched tumor tissue, which can often be inaccessible or challenging to obtain.

The validation study analyzed banked samples from 64 patients with advanced head & neck, breast, ovarian, melanoma, or other solid tumors who received pembrolizumab at Princess Margaret Cancer Centre, University Health Network in Toronto, Canada. Blood samples were collected pre-treatment and prior to every three treatment cycles starting at cycle 3 of treatment.

Key Findings

Key findings from the trial indicate that a decrease in ctDNA levels from baseline to the pre-cycle 3 assessment was significantly correlated with improved outcomes. Specifcally, the odds of achieving an objective response were markedly higher, with an odds ratio of 31.77 (95% CI: 3.71–4173.19, P=0.0003). Similarly, the likelihood of experiencing clinical benefit was also elevated, reflected in an odds ratio of 15.55 (95% CI: 3.31–151.52, P =0.0002).

"The study supports the use of the test for response monitoring and the early identification of patients who are not responding to immunotherapy and could benefit from a different treatment approach. The test may thus be a useful tool to support clinical decisions regarding therapy continuation or discontinuation to optimize patient outcomes, and perhaps avoid unnecessary toxicity," Enrique Sanz-Garcia, MD, medical oncologist and clinician investigator, Princess Margaret Cancer Centre, University Health Network, said in a release.

These associations were robust across univariate analyses and remained significant in multivariable models, with the exception of overall survival.

By validating a commercial-grade, tissue-agnostic plasma cfDNA methylation platform, oncologists may now have a powerful tool at their disposal for immunotherapy response monitoring. This advancement not only facilitates earlier and more informed treatment decisions but also has the potential to enhance patient outcomes through timely interventions.

As the landscape of metastatic solid tumor treatment continues to evolve, the integration of ctDNA testing into routine clinical practice could represent a significant step forward in personalized cancer care. This pivotal research underscores the need for ongoing exploration of liquid biopsies in oncology, particularly as the demand for less invasive methods of monitoring treatment response grows.

REFERENCES

1. Adela announces study published in NPJ Precision Oncology clinically validating its tissue-free test to monitor immunotherapy response in advanced solid tumors. News release. March 3, 2026. Accessed March 4, 2026. https://tinyurl.com/nhkwx2md

2. Stutheit-Zhao EY, Zhong Y, Melton CA, et al. Clinical validation of a tissue-agnostic genome-wide methylome enrichment assay to monitor response to pembrolizumab. NPJ Precis Oncol. Published online February 13, 2026. doi:10.1038/s41698-026-01327-y