PGDx Liquid Biopsy Test Shown to Predict Patient Response to Checkpoint Blockade Drugs

PGDx Liquid Biopsy Test Shown to Predict Patient Response to Checkpoint Blockade Drugs
CTLA-4 (Cytotoxic T-lymphocyte-associated protein 4, CD152) protein. CTLA4 blocking antibodies are used in cancer therapy (immune checkpoint blockade therapy). Stylized combination of a semi-transparent surface model with a cartoon representation. Cartoon: gradient colouring (N-terminus blue, C-terminus pink).

A study published by Clinical Cancer Research, a journal of the American Association for Cancer Research (AACR), demonstrates that Personal Genome Diagnostics’ (PGDx) liquid biopsy technology can detect microsatellite instability (MSI) in circulating tumor DNA (ctDNA), and by doing so can estimate the likelihood of both an immediate and durable response to immune checkpoint blockade in cancer patients with MSI. The new research further reinforces the utility of liquid biopsies as a non-invasive approach to genotyping and monitoring patients with advanced forms of cancer.

“Microsatellite instability and high tumor mutation burden (TMB) are promising pan-tumor biomarkers that are used to identify patients who may be candidates for treatment with immune checkpoint blockade,” said John Simmons, Ph.D., vice president of translational medicine for PGDx in a press release. “Obtaining samples via tumor biopsy can be challenging in people with advanced cancer, so this liquid biopsy test is a tool that can help doctors select the best therapy for their patients.”

Microsatellite instability, along with mismatch repair (MMR) deficiency were the first pan-cancer biomarker indications approved for treatment of patients with the immune checkpoint inhibitor, pembrolizumab. Given the challenges of obtaining tissue samples for many cancer patients, clinicians have sought alternative testing methods that can provide the information they need to determine whether a specific therapy is indicated for a patient. The current study examined the viability of developing a liquid biopsy test that could identify patients with high MSI and tumor mutation burden (TMB) as a method to determine potential patient response to treatment with immune checkpoint blockade. In addition, the liquid biopsy method using ctDNA can also help clinicians monitor ongoing patient response to treatment and provide information much earlier when the therapy is no longer having the desired effect.

“Our study further demonstrates that ctDNA is a more rapid and dynamic method to determine response to therapy, and in particular to immune checkpoint blockade, in comparison with a protein biomarker or radiographic imaging,” said Andrew Georgiadis, the study’s first author and a senior scientist at PGDx.

According to the study abstract, PGDx and affiliated researchers developed a hybrid-capture–based 98-kb pan-cancer gene panel including targeted microsatellite regions. The team also developed a multifactorial error correction method and a novel peak-finding algorithm that was capable of identifying rare MSI frameshift alleles in cell-free DNA (cfDNA).

“We have described the development of an analytical method for simultaneous detection of MSI and TMB-High directly from cfDNA and demonstrated proof of concept for the clinical utility afforded through these analyses for the prediction of response to immune checkpoint blockade,” the study authors concluded.

Johns Hopkins, Memorial Sloan Kettering Cancer Center, and other institutions, contributed to the study, in addition to researchers from PDGx.