Multi-Cancer Screening Tests Are Getting Closer to Reality

The hope of developing a single blood test capable of detecting multiple types of early-stage cancer is getting closer to becoming a reality. Two hopeful players, GRAIL (Menlo Park, Calif.) and Thrive (Cambridge, Mass.), recently made big announcements to coincide with the American Society of Clinical Oncology’s (ASCO’s) annual meeting (May 31 to June 4; Chicago).

With a head start, GRAIL released new data at ASCO regarding its test’s performance on the first 2,300 patients in ongoing clinical trials.

Data reported at ASCO are based on initial analysis of 2,301 participants from a sub-study of the Circulating Cell-free Genome Atlas (CCGA) study. Analysis included 1,422 participants with more than 20 cancer types across all stages plus 879 participants without diagnosed cancer. Analysis also broke out 12 pre-specified, deadly cancer types—anorectal, colorectal, esophageal, gastric, head and neck, hormone receptor negative breast, liver, lung, ovarian, and pancreatic, plus multiple myeloma and lymphoid neoplasms—which, together, account for approximately 63 percent of all cancer deaths in the United States, the company says.

The test showed a very high specificity of at least 99 percent. However, across all 20 cancer subtypes and stages, the overall detection was 55 percent, while the overall detection rate for the 12 pre-specified deadly cancer types across all stages was 76 percent. GRAIL’s ability to correctly identify cancer type depended on both cancer stage and the tissue of origin. Stage 1 cancers were predictably the hardest to detect, with the test doing so only 34 percent of the time versus more than 90 percent of the time for metastatic, stage 4 cancers. For earlier cancers—stages 1 through 3—head and neck cancer was most easily detectable, while lung cancer was the hardest.

Additionally, the company announced it has narrowed its technological approach. Previously, the company pursued three different detect methods—targeted DNA sequencing, whole-genome sequencing, and methylation analysis. The company announced it will pursue the latter, methylation analysis, which covers 30 million sites across the genome. Additionally, the test uses a proprietary database and machine-learning algorithms to both detect the presence of cancer and identify the tumor’s tissue of origin.

“Based on these positive data, we plan to advance development of our test toward commercialization,” Jennifer Cook, the recently departed CEO at GRAIL, previously said in a statement.

The test was able to provide a tissue of origin result across more than 20 cancer types for 94 percent of all cancers, with the test correctly identifying the tissue of origin in 90 percent of these cases. The tissue of origin accuracy was consistent regardless of stage ranging.

GRAIL is using its capital for further, large-scale clinical trials.

• GRAIL is conducting three pre-planned, sub-studies within CCGA to further train and validate its test. The 15,000-person trial completed enrollment at 142 centers across the United States and Canada.
• The prospective STRIVE study completed enrollment of approximately 100,000 women at the time of their screening mammogram across 37 sites in the United States. STRIVE is designed for clinical validation of GRAIL’s multi-cancer test in an intended use population with data reporting anticipated in 2020.
• The prospective SUMMIT study is enrolling 50,000 cancer-free men and women in the United Kingdom. Approximately half of the participants will be people at high risk of lung and other cancers due to a significant smoking history. This trial is designed for clinical validation of the multi-cancer test in a second intended use population and to evaluate clinical utility of the test in a high-risk population.

GRAIL Is Not the Only Player Seeking to Enter the Multi-Cancer Screening Space
On May 30, Thrive announced it closed $110 million in a series A round of financing to advance development and commercialization of its CancerSEEK liquid biopsy test.

CancerSEEK combines targeted DNA and protein analysis in a liquid biopsy test to detect multiple cancer types at earlier stages of disease. The Johns Hopkins University spinout says it will integrate real-world data and machine learning to continue to improve the test over time and to create a cost-effective, “comprehensive care solution” for primary care physicians.

Two High-Profile Players

• Both spun out of well-known entities — GRAIL from Illumina in 2016 and Thrive from Johns Hopkins University this year.
• Both raised enormous amounts of money — GRAIL more than $1.5 billion over three years and Thrive $110 million in its first round.
• Both have liquid biopsy tests with accurate screening performance — 99 percent specificity.
• Both received U.S Food and Drug Administration’s Breakthrough Device designation.

The test assesses eight protein biomarkers and tumor-specific mutations in circulating DNA. Last February, test performance was reported in Science. In the study of 1,000 patients previously diagnosed with cancer and 850 healthy control individuals, CancerSEEK detected cancer with a sensitivity ranging from 69 percent to 98 percent for the detection of five cancer types (ovary, liver, stomach, pancreas, and esophagus) for which there are no screening tests available for average-risk individuals. Specificity was 99 percent. Additionally, CancerSEEK determined the anatomic location of the cancer in 83 percent of the patients.

Currently, CancerSEEK is being evaluated in DETECT, a study of 10,000 healthy women. The trial is being conducted in conjunction with Geisinger. Results will further inform test performance and provide insight into integration of test findings into clinical care. CancerSEEK previously received Breakthrough Device designation from the U.S. Food and Drug Administration for the detection of genetic mutations and proteins associated with pancreatic and ovarian cancers.

Takeaway: New evidence provides positive performance data for two blood tests capable of screening for multiple types of cancer. These well-funded companies continue large-scale clinical trials in the march toward commercialization.