TORONTO, April 13, 2023 – Geneseeq co-published a study with Princess Margaret Cancer Centre in the JCO Precision Oncology journal, investigating the use of ctDNA as a prognostic biomarker for immunotherapy in early-phase clinical trials.

Immunotherapy has shown promising results in multiple cancer types, including melanoma, lung cancer, and gastric cancer by harnessing the body’s own immune system to fight cancer. Early-phase clinical trials (PhaseI/II) develop effective immunotherapies by evaluating dose-limiting toxicities and antitumor activity to establish the recommended phase 2 dose (RP2D) for further clinical development. Early changes in circulating tumor DNA (ctDNA) levels over time (kinetics) have been shown to associate with long-term treatment outcomes in patients receiving chemotherapy and targeted therapy. Similar findings have been observed in patients treated with immunotherapy (IO), including immune checkpoint inhibitors (ICIs) targeting programmed cell death 1 (PD-1) or programmed cell death ligand 1 (PD-L1) in melanoma, lung, and gastric cancers.

In this study, the Princess Margaret Cancer Centre researchers analyzed plasma samples from 81 patients with advanced solid tumors who were being treated with investigational immunotherapy agents in 37 different Phase I/II trials. Using the GeneseeqPrime™ panel, the researchers evaluated the variant allele fraction (VAF) of mutations in ctDNAs at baseline and before the second cycle of treatment (3-4 weeks) with a sequencing depth of around 5000X. ctDNA was present in 75.3% of the samples and a decreased mean VAF(mVAF) from baseline to pre-cycle 2 was associated with longer progression-free survival and overall survival compared to an increased mean VAF. This overall survival increased significantly when there was a greater than 50% decrease in mean VAF. Interestingly, the researchers did not find significant differences in the median mVAF change rate between patients with hyper progressive disease and those with stable or responding diseases.

“Our results suggest that very early changes in ctDNA levels, as determined by a tumor-naive assay, may be a useful predictor of treatment benefit in phase I/II immunotherapy trials. This approach may help identify responders to immunotherapy at an early stage, allowing for the optimization of treatment strategies and improving patient outcomes”, says Dr. Qiuxiang Ou, author and associate director of Geneseeq Research Institute.