Pivotal Study Examines Blood Test as CRC Screening Method

AmirAli Talasaz, PhD, president and chief operating officer of Guardant Health

AmirAli Talasaz, PhD

In an effort to improve colorectal cancer (CRC) screening rates via a less invasive method, the registrational ECLIPSE (NCT04136002) is evaluating the performance of the LUNAR-2 blood test in detecting CRC in average-risk adults.¹

The prospective, multicenter, 10,000-patient ECLIPSE trial is expected to enroll patients between the ages of 45 and 84 who are at average risk of developing CRC and screened with LUNAR-2. If positive, Guardant Health, the developer of the test, stated in a press release that it expects the data will support a premarket approval submission to the FDA.

“Colorectal cancer screening is known to be effective in saving lives. Unfortunately, one-third of adults do not adhere to national screening recommendations. Because blood tests are a routine part of a patient’s office visit, we believe our blood test could be easily integrated into an already established workflow which will lead to significantly increased screening rates,” AmirAli Talasaz, PhD, president and chief operating officer of Guardant Health, stated in the press release. “We are excited about the performance of the LUNAR-2 assay and look forward to the results of this large prospective study to drive both payer coverage and clinical adoption.”

The United States Preventive Services Task Force recommends CRC screening in average-risk adults starting at age 50 and then regularly thereafter. However, although early detection has been shown to improve survival, one-third of adults in the United States are not regularly getting screened.

In the ECLIPSE trial, investigators will perform a blood draw prior to the patient undergoing standard colonoscopy, as well as all associated preparatory medications, and retrospectively compare the performance characteristics of the LUNAR-2 assay with the results of the index colonoscopy. Patients on the study who receive a positive circulating tumor DNA (ctDNA) result should undergo further testing with colonoscopy.

To be eligible for enrollment, patients must be aged between 45 and 84 years at time of consent and intend to undergo screening colonoscopy, as well as be considered average-risk for developing CRC, willing to consent to blood draw, and consent to 2-year follow-up as per protocol.

Those who are undergoing colonoscopy for investigation of symptoms, underwent colonoscopy within the last 9 years, had a positive Fecal Immunochemical Test/Fecal Occult Blood Test within the last 6 months, completed Cologuard or Epi proColon testing in the prior 3 years, a history of CRC or any malignancy, a known diagnosis of inflammatory bowel disease, positive family history of CRC, and known hereditary/germline risk of CRC are some exclusion criteria for the study.

The coprimary endpoints are sensitivity of CRC detection and specificity of advanced neoplasia detection. Secondary endpoints include positive and negative predictive value of CRC detection and sensitivity and specificity of advanced adenoma detection. Also, 1- and 2-year outcomes of patients post-procedure will be collected as secondary endpoints to investigate the possibility of incidental, non-CRC cases and interval cancers that had not reached clinical threshold for detection at the time of the index colonoscopy.

The study is estimated to have a primary completion data of 2022.

“The LUNAR-2 assay has shown high sensitivity in detecting colorectal cancer and we are ready to make this our first indication for the early detection of cancer in asymptomatic individuals. We believe it is an ideal disease to address first, because the low compliance of current approaches creates a clear unmet medical need, the tumor biology is well captured by our blood-based technology, and existing pathways are in place for both downstream intervention and reimbursement, making it easier to drive clinical use,” Guardant Health CEO Helmy Eltoukhy, PhD, stated in the press release. “Initiating this study marks a major step forward in our mission of conquering cancer with data.”

Prior data have demonstrated that an assay analyzing somatic genomic, epigenomic, and fragmentomic signals from ctDNA in the blood is effective in detecting early-stage CRC.² In this analysis, plasma samples were collected from 72 patients with stage I, II, III, or IV CRC before and 4 weeks after surgery; 35 age-matched cancer-free controls were also similarly analyzed in the test set.

Results showed that of 72 patients, 62.5% were male, and the median age at CRC diagnosis was 61.5 years (range, 36-85). A total 52.8% of patients had stage I/II, 40.3% were stage III, and 6.9% had stage IV CRC. At a median postsurgery follow-up of 314 days, 49 of 50 patients with postsurgical samples had clinical follow-up available. With the assay, the presurgery ctDNA detection rate was 94%; this was stratified as 97% in stage I/II disease, 90% for those with stage III disease, and 100% in patients with stage IV CRC. The epigenomic analysis was found to significantly enhance ctDNA detection relative to somatic mutational analysis alone at 94% versus 56%, respectively (P <.0001). Moreover, the specificity in the age-matched cancer-free controls was 94%.

References

1. Guardant Health Initiates ECLIPSE Pivotal Study for its LUNAR-2 Blood Test for Colorectal Cancer Screening. Guardant Health. Published October 24, 2019. https://bit.ly/2BIIR76. Accessed October 24, 2019.
2. Kim ST, Raymond VM, Park JO, et al. Combined genomic and epigenomic assessment of cell-free circulating tumour DNA (ctDNA) improves assay sensitivity in early stage colorectal cancer (CRC). Clin Can Research. 2019;79(13). doi: 10.1158/1538-7445.AM2019-916.