Transcript

Hi, my name is William Harris, and I am a gastrointestinal medical oncologist at University of Washington Seattle Cancer Care Alliance and Fred Hutchinson Cancer Research Center in Seattle.

It is a pleasure to talk to you today about one of our abstracts from GI ASCO 2021, which is a trial-in-progress abstract, highlighting an ongoing project. The abstract is entitled, "A Feasibility Study of Multi-Platform Profiling Using Biospecimens from Patients with Resected Biliary Tract Cancer."

Again, this is an ongoing project. We presented the layout of how we are obtaining testing for our patients for this project. Really, this is a feasibility study investigating multiple platforms to try to obtain more information about multiple clinical aspects of patients with resected biliary tract cancer.

The key components of this study are that we are conducting a prospective assessment, looking at a few different advanced platforms to try to decipher their utility in either predicting recurrence after resection of biliary tract cancers and looking into whether organoid screens derived from resected tumor specimens can correlate with clinical outcomes such as benefit from adjuvant chemotherapy, and subsequent response to first-line systemic therapy and subsequent targeted therapeutics.

In terms of the relevant issues that we are addressing, the key components here are that we are trying to correlate multiple different platforms prospectively on a cohort of about 20 patients who have undergone resection for biliary tract cancer. This can include intrahepatic, extrahepatic cholangiocarcinomas and gallbladder carcinoma.

In terms of the existing data that led myself and my co-investigators at our institution to design this study, the relevant information applies to the different platforms. There is clearly a need to identify who is at higher risk of recurrence after resection of either cholangiocarcinoma or gallbladder carcinoma.

From the other studies and other malignancies, we have seen that there's been significant improvement in our ability to assess circulating tumoral DNA to detect minimal residual disease. I would point you to some of the data specifically from colorectal cancer, although it is evolving in other malignancies as well, which has shown that we can detect minimal residual disease after resection.

Certainly, from the colorectal-cancer data, when we use high-quality platforms, we can really identify patients who are at much higher risk of progressing and can develop some lead time in identifying which patients are likely to progress after initial potential curative resection.

One of the things I will highlight about this study is the platform itself. In terms of assessing circulating tumoral DNA, we are using a relatively sensitive test that is really designed more specifically to identify minimal residual disease. In this case, we are using a Signatera test.

This looks at the resected tumor and develops a patient-specific molecular profile that is quite sensitive at identifying residual circulating DNA. There is some data at GI ASCO looking at some other platforms in cholangiocarcinoma, suggesting that a proportion of patients can have circulating tumoral DNA detected through other platforms.

Our hope is that this is perhaps a more sensitive assay and that we can capture who is at risk of recurrence with our cohort. Another important component of this is the development of organoids from the resected tumor. This is another separate question we are addressing, looking at can we grow patient-specific organoids from the resected tumor specimen.

Our primary endpoint for this study is really feasibility in establishing organoids and identifying the rate of circulating tumoral DNA postoperatively. In terms of the organoids themselves, we can grow an organoid and drug it against a specific panel designed to look at alterations relevant to biliary tract cancers.

Then we can track these patients prospectively and try to correlate how did they do in terms of adjuvant chemotherapy. Did our organoid screen correlate in terms of sensitivity to the drugs we use in the adjuvant setting? Should these patients progress? We will have information on sensitivity to the agents we select in first-line systemic therapy for metastatic disease and in subsequent lines.

Another question is does the organoid screen identify new potential targets that might be relevant to patients with biliary tract cancer that are not identified based upon other more routine assays, such as specific sequencing of the tumor for actionable mutations?

What this is is a pilot study looking at the feasibility of some promising interventions in profiling tumor or assessing risk of recurrence. This would be hypothesis-generating information to help us design future trials that are relevant to this population. I will note that organoids, and in this case, we are using a platform through SEngine, have looked promising.

There is some data that has been published in abstract form and in journals, regarding retrospective correlation of organoid sensitivities and clinical outcomes upon exposure to specific therapeutics. This is a prospective cohort, so high-quality data to support further development. In terms of the real-world applications of these findings, really, this is not an interventional study.

This is an observational study. As we get more clinical data, and can correlate it with our organoid screens and circulating tumoral DNA assessments, it's possible that we could start to think about incorporating some of these biomarkers into future trials and validate in larger cohorts their efficacy in selection of therapy. That is a potential, promising next step.

I'll note that Dr. Adam Diehl was the first author on this abstract. Dr. Gentry King helped develop the circulating tumoral DNA assessments and is co-author on this study, along with myself. I would like to thank our surgeons at University of Washington and our other colleagues, who have been instrumental in helping move this forward.

I will also note that we are assisting some colleagues at University of Illinois, Chicago, in creating a sister cohort, and we anticipate we may be able to pool this data to provide more robust analysis.