So in head and neck cancer, there is an unmet need for treatment optimization that improves survival while reducing treatment-related toxicities across two different subtypes of head and neck cancer, HPV-positive disease, which has a more favorable prognosis, as well as HPV-negative or viral-independent disease, which has a worse prognosis than head and neck cancer. And one of these tools to help with treatment optimization more recently has been using non-invasive blood-based assessments, liquid biopsy or minimal residual disease or other terms as such, of circulating tumor DNA to try to help with determining treatment optimization...
So in head and neck cancer, there is an unmet need for treatment optimization that improves survival while reducing treatment-related toxicities across two different subtypes of head and neck cancer, HPV-positive disease, which has a more favorable prognosis, as well as HPV-negative or viral-independent disease, which has a worse prognosis than head and neck cancer. And one of these tools to help with treatment optimization more recently has been using non-invasive blood-based assessments, liquid biopsy or minimal residual disease or other terms as such, of circulating tumor DNA to try to help with determining treatment optimization. Now, we’ve discovered that this has utility both for HPV positive and for HPV negative disease. For HPV positive disease, much of the focus has been on leveraging viral DNA to generate tumor-agnostic blood tests. Basically, blood tests are able to leverage the viral DNA in order to develop quite specific and sensitive assays. We’ve now found that many of these commercial assays, both those that are based on dPCR and those that are based on NGS, are exquisitely sensitive and specific in the surveillance setting after definitive treatment for HPV-related head and neck cancer. We’ve also found that mid-treatment dynamics also seems to be predictive. And so the next phase is, number one, developing more sensitive assays for HPV-related head and neck cancer that are more sensitive than the currently commercially available assays, and then generating trials that try to explore how we can actually use these results to improve outcomes for patients. And there’s two recent examples I’ll highlight in this call. One is the recent REACT trial, which used ctDNA clearance mid-treatment to select higher clinical risk patients for de-escalated radiation and was quite promising in that regard. The other is for patients that are MRD-positive after treatment, and we have a trial that’s enrolling in that setting as well. Now, for HPV-independent head and neck cancer, it’s been a bit more challenging because we don’t have the viral DNA in order to generate tissue-agnostic approaches. But nonetheless, we’ve learned quite a bit about this as well. Tumor-informed approaches seem to be quite feasible in the surveillance setting to predict occurrence. We’ve also found that tumor-informed assays, that early dynamics within two or even one cycles of treatment, is strongly predictive of clinical benefit, immunotherapy-based treatment in the recurrent metastatic setting. And there’s also an unmet need in the viral-independent setting as well to generate, to develop, and validate more sensitive and specific assays there as well. We will be seeing results at AACR for the MERIDIAN trial, which is a trial that is exploring not only MRD after definitive treatment for head and neck cancer, but is also exploring testing a PD-1 TIGIT bispecific for patients who are MRD positive, and we look forward to seeing those interim results presented at AACR at this meeting as well. So those are some of the highlights that I’ll try to explore, sort of where things are currently, what got us here, where I think the biggest unmet needs are, and most importantly, what some of the key investigations are moving forward to try to explore how do we, again, use these results to adapt treatment to improve outcomes for patients.
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