Checkpoint blockade immunotherapy uses drugs to take the brakes off a patient’s immune system so that the immune cells can then recognize and attack tumor cells. However, the majority of non-small cell lung cancer (NSCLC) patients either will not respond to these therapies or will have tumors that develop resistance after initial success with immunotherapy. Valsamo Anagnostou, MD, PhD, assistant professor of Oncology at the Sidney Kimmel Cancer Center at Johns Hopkins, wanted to develop a better way to monitor patients’ outcomes with immunotherapy treatment and identify cancer recurrences earlier.
Currently, visualizing the cancer through imaging and re-biopsying the tissue are two ways that physicians can monitor a patient’s progress, but they are not ideal.
“Imaging is not always reflective of clinical outcomes and tissue biopsy-based assessments are one-time snapshots of what is happening with the tumor,” explains Dr. Anagnostou. “We wanted to develop a dynamic way to track the patient’s progress to know if the immunotherapy treatment is working.”
Dr. Anagnostou’s preliminary work suggested that a simple blood test to look at the levels of circulating tumor DNA (fragments of DNA that are released from dying tumor cells that circulate in a patient’s bloodstream) could be an effective way to monitor patients undergoing checkpoint blockade immunotherapy.
After applying for and being awarded a 2017 Career Development Award from LUNGevity Foundation, Dr. Anagnostou was able to continue studying circulating tumor DNA (ctDNA) to identify key changes in the bloodwork of NSCLC patients.
Using ultra-sensitive next-generation sequencing approaches, Dr. Anagnostou and her colleagues found that patients who are responding well to checkpoint blockade immunotherapy show a significant decrease in ctDNA levels. The team also found that ctDNA would return to high levels in patients whose tumors had developed resistance to immunotherapy treatment. In addition, the researchers found that the ctDNA remained present in the bloodwork of patients who were not responding well to immunotherapy. Dr. Anagnostou and her research team have used these findings to develop a blood test that can be used to monitor patients during immunotherapy.
After these results were published in Cancer Research, a highly-respected peer-reviewed scientific journal, in March of 2019, Dr. Anagnostou and her team continued to refine their work.
Now, in 2020, the ctDNA-based blood test is being assessed in a phase 2 clinical trial (trial number: NCT04093167) that is expected to enroll approximately 200 NSCLC patients. The trial is a unique approach that has never been used before in patients receiving immunotherapy. The first stage of the trial will confirm that changes in ctDNA levels can be used to determine how the cancer is responding in patients treated with pembrolizumab (Keytruda®), a checkpoint blockade immunotherapy. The second stage of the trial will utilize the liquid biopsy test to determine if patients whose cancer is not responding well to pembrolizumab might see improvements through different treatment options.
“We are so excited about this clinical trial and about the progress we are making and we are so appreciative of LUNGevity. The Career Development Award was instrumental in supporting the initial research that led to this new clinical trial,” says Dr. Anagnostou. “Our goal is to really take the research that we do in the lab and translate it to the clinic to help patients. And that is exactly what this clinical trial is designed to do.”
Related Reading:
- The Impact of the LUNGevity Career Development Award
- Research Underway to Improve Immunotherapy Outcomes for ALK-Positive Lung Cancer
- LIving with Lung Cancer for Seven Years
Juhi Kunde, MA, is a science writer for LUNGevity.