What I presented today at ESMO was the initial analysis of the PATHFINDER II study which is a registrational study looking at the safety and efficacy of a multi-cancer early detection test, or MCED test, in an intended use population. Just as a little bit of background, the Grail Galleri multi-cancer related detection test is a blood test that looks at clues for cancer. Essentially it's a circulating free DNA test looking at methylation profiles on that circulating free DNA that’s shed into the bloodstream. Using next generation sequencing and machine learning the test has an ability to detect cancer signals and if a cancer signal is detected the MCED test was also able to provide a cancer signal origin prediction that provides the investigators and the providers an idea as to where the cancer signal could be coming from to help hone in on the further diagnostic testing.
The PATHFINDER II study which we presented the initial analysis for of the first 25,000 patients who have a one-year follow-up. Just as a step back, the PATHFINDER II is the largest US interventional MCED clinical trial to date, enrolling nearly 36,000 participants from 32 healthcare systems over 32 months. Participants in the PATHFINDER II study were at least 50 years of age with no clinical suspicion of cancer nor a diagnosis of cancer within three years. All of the patients were provided with a Galleri multi-cancer early detection test and the results were returned back to them. For those that had a positive MCED result, and based on the CSO prediction, the cancer signal origin prediction, the investigators worked up their cancer to identify that cancer.
All participants in the PATHFINDER II study will be followed for three years to assess their cancer status to inform the test metrics. They’re also going to be followed for patient-reported outcomes such as adherence to recommended cancer screening programmes. The primary endpoint of the PATHFINDER II study is to assess the safety and efficacy of the MCED test.
For this initial analysis we assessed the first 25,000 participants who had one year of follow-up. For this cohort of patients the cancer signal detection rate was a little less than 1%. Out of that 1%, patients that had a positive MCED test result, the positive predictive value was 60%, meaning that if a participant had a positive MCED test they had a six out of ten chance of actually having a cancer following the work-up. In total in the one-month timeframe 329 cancers were identified, 200 of those, or 61%, were screen detected cancers. The MCED test detected 133 cancers and the MCED test was able to increase the number of screening detected cancers by more than sevenfold when considering the four cancers that we’re currently screening for such as lung cancer, breast cancer, cervical and colorectal cancer.
Furthermore, the cancers that were identified from the MCED test were clinically relevant. The majority of them were early stage and the majority of those were of cancers that don’t have recommended screening strategies. By and large, these are cancers that when caught early treatment is easier and outcomes are better. Furthermore, the study assessed the test safety and less than 1% of the 25,000 participants had an invasive procedure as a result of the MCED test. The study also found that the accuracy for that cancer signal origin prediction was highly accurate where it accurately predicted where the cancer was coming from in 92% of the participants that had a true positive finding.
In summary, the PATHFINDER study, which is the largest multi-cancer early detection intervention study to date, was able to increase the number of screen detected cancers by sevenfold, had a robust positive predictive value of 62% which is higher than what we’ve seen previously with this test and orders of magnitude higher than our current single cancer screening methodologies. The test was certainly found to be safe. Really, the study illustrates the MCED test clinical utility and potential to improve outcomes, especially when implemented on a population level.
What is the turnaround time for the tests?
For the study participants the turnaround time was about three weeks from blood test to report.
What might the implications of these findings be?
I certainly see the utilisation of this test not as a replacement for mammograms, not as a replacement for colonoscopies but really to fill that unmet need, to screen for cancers that we’re not screening for at all right now. I envision this test to be used in a complementary fashion with those screening tests that we know and we trust and we use.
