Yeah, it’s a great question. In HPV positive disease, the early dynamics of circulating tumor HPV DNA do seem to be a helpful dynamic biomarker of response. And this has been demonstrated now for a number of years that that mid-treatment time point, whether it’s clearance by over 95% decrease, whether it’s complete clearance, these seem to be predictive of progression-free survival...
Yeah, it’s a great question. In HPV positive disease, the early dynamics of circulating tumor HPV DNA do seem to be a helpful dynamic biomarker of response. And this has been demonstrated now for a number of years that that mid-treatment time point, whether it’s clearance by over 95% decrease, whether it’s complete clearance, these seem to be predictive of progression-free survival. And so that has been the underpinning of, again, some trials that are reported out or one trial that is reported out and others that are currently ongoing to explore, can you use the mid-treatment dynamics to optimize treatment or de-escalate treatment for HPV-positive disease? Additionally, patients who don’t clear their HPV DNA might be candidates for escalation, and there’s a number of trials at our site and others that are trying to explore that question, such as incorporating immunotherapy, for example, in the context of prospective clinical trials. For HPV-negative disease, there’s more work to be done on understanding the mid-treatment kinetics of ctDNA for HPV-negative disease and how that might help intensify or de-intensify treatment. Again, the Meridian trial, which will be reported out at AACR, at least the initial report, will hopefully give a little bit of insight into that particular question. So we look forward to hearing those results as well. And I’ll just highlight in the recurrent metastatic setting, we actually have quite a bit of evidence that dynamics, whether it’s increasing or decreasing ctDNA, both for HPV positive and for HPV negative, seems to be predictive. This actually set the stage for a trial called the Synergy trial, which we recently reported out at a recent head-neck meeting, which tested adaptive escalation, de-escalation of chemoimmunotherapy every two cycles based on the ctDNA dynamics. That trial did find quite promising both efficacy as well as reduced toxicity compared with historical controls. And so we look forward to more mature data in that trial to try to inform, you know, how can we use ctDNA dynamics also in the recurrent metastatic setting to improve outcomes, both to enhance the, for example, immunogenicity of systemic therapy, while at the same time minimizing the toxicity associated particularly with the cytotoxic chemotherapy component.
This transcript is AI-generated. While we strive for accuracy, please verify this copy with the video.
