• Highlights the use of Invitae's personalized cancer monitoring (PCM) technology to correlate clinical outcomes with minimal residual disease (MRD) presence
• The analysis demonstrates the utility of ctDNA as a highly sensitive and specific biomarker for cancer recurrence
• Study validates the need for MRD assays; the company to continue to leverage its differentiated PCM technology in pursuing opportunities across multiple indications in the clinical oncology market

SAN FRANCISCO, April 13, 2023 /PRNewswire/ -- Invitae (NYSE: NVTA), a leading medical genetics company, today announced new research published in Nature describing the first use of the company's personalized cancer monitoring (PCM) platform to demonstrate the utility of ctDNA as a biomarker for cancer recurrence in a large cohort of patients with stage I-III non-small-cell lung cancer (NSCLC) followed for up to five years. 

The research technology used in the study leverages a patient-specific panel developed to identify variants from a patient's own tumor rather than a static gene panel. This study leveraged Invitae's PCM platform to assess panels of up to 200 variants, a size unique to this platform at the time the study was conducted, and was optimized for maximum performance. Since then, Invitae has commercialized its laboratory developed test utilizing panel sizes of up to 50 variants. In this publication, sensitivity and specificity of >99.9% was achieved at 0.008% variant allele frequency (AF) with 60ng cfDNA input and 0.03% variant AF with 10ng cfDNA input using a 50 variant patient-specific panel.

"The use of our PCM platform in this large study shows the value of our technology which providers can use to identify early detection of residual disease and cancer recurrence through a liquid biopsy and improve their patient's overall cancer journey," said Robert Daber, Ph.D. DABMG, chief science officer at Invitae. "These results validate the need for products like PCM that create a data-driven treatment process for patients and physicians alike through ongoing cancer monitoring."

Patients enrolled in the study had plasma analyses performed before surgery and 141/197 patients (including 75 with NSCLC recurrence) had repeated postoperative plasma analyses performed with a median of six time points. Using new phylogenetic tracking technologies including patient specific anchored-multiplex PCR (AMP), these tumor-specific clonal and subclonal mutations were identified in combination with a novel tool (ECLIPSE) to extract clonal composition in the context of the low ctDNA levels in patients with recurrent NSCLC. The versatility of the AMP technology permitted the study of patient plasma samples across a range of individual panel sizes (72 to 201, median 200).

Landmark MRD analyses were performed on 108 patients (analyses of plasma samples collected within 120 days of surgery). Of the 51 patients experiencing lung cancer relapse, results showed that ctDNA was detected in nearly half of the patients. Utilizing the early landmark analysis window to forecast eventual relapse demonstrated a positive predictive value of 93% and a negative predictive value of 68%. These results are further improved by continued surveillance beyond the landmark period. Specifically, 20% of patients who had landmark negative results were identified with impending disease relapse based on monitoring samples collected periodically for up to five years, which demonstrates the importance of longitudinal ctDNA surveillance. ctDNA was detected in relapsing patients prior to standard clinical diagnosis via imaging by a median time of almost four months (119 days, range 0 to 1137 days).

Clinical sensitivity and specificity were also assessed in this study. Clinical specificity was assessed in 61 patients without evidence of disease in whom ctDNA was not expected to be detectable. This group of 61 patients included 42 recurrence-free patients and 19 patients who were disease-free at the time the ctDNA was assessed but subsequently developed new primary cancers during follow-up. The study reports a specificity of 95%, but after removing a patient with known anomalies, 58 out of 60 patients were negative for ctDNA, giving a specificity of 96.7% (95CI 88.64-99.08%). Clinical sensitivity was assessed in 70 patients expected to be ctDNA positive including 66 patients with recurrent cancer and four patients with incomplete resections. The paper reports a minimum sensitivity of 84%. Additional filtering of qualifying samples (including requiring ctDNA sampling within 100 days of relapse) yields 59 samples having positive ctDNA results out of a total of 63 patients, for a sensitivity of 93.6% (95CI 84.8-97.5%).

The findings suggest that future management strategies for early-stage adenocarcinomas should take tumor-informed ctDNA detection into account to reduce disease recurrence rates in patients identified to be at high risk.

About the TRACERx clinical study

TRACERx (TRAcking non-small cell lung Cancer Evolution through Therapy [Rx]) (NCT01888601) is a multi-center, prospective study of patients with primary non-small cell lung cancer (NSCLC) within the UK National Health Service that aims to define the trajectories of lung cancer through multiregional and longitudinal tumor sampling and genetic analysis. One goal was to determine whether circulating tumor DNA (ctDNA) could serve as a phylogenetic biomarker in early-stage NSCLC. High-resolution ctDNA methods were applied to track a median of 200 tumor-specific mutations from 1,069 plasma samples from 197 patients enrolled in the study. Analyses of plasma samples collected within 120 days post-surgery revealed ctDNA detection in 25% of patients, including 49% of all patients who experienced clinical relapse. A landmark positive status associated with early-NSCLC relapse within the first postoperative year and three to six monthly ctDNA surveillance of patients (for up to five years) identified impending disease relapse in 20% of landmark negative patients.

About PCM™

Invitae's Personalized Cancer Monitoring (PCM™) assay is designed to detect minimal residual disease (MRD) in patients. The oncology product uses a novel set of personalized assays based on a patient's tumor to detect circulating tumor DNA (ctDNA) in blood, assisting with risk stratification, assessing response to treatment and detecting residual disease and cancer recurrence.

About Invitae

Invitae (NYSE: NVTA) is a leading medical genetics company trusted by millions of patients and their providers to deliver timely genetic information simplified by digital technology. With accurate and actionable answers to strengthen medical decision-making, Invitae gives individuals and their families powerful, personalized insights that could improve and extend their lives. Invitae's genetics experts apply a rigorous approach to data and research, serving as the foundation of their mission to bring comprehensive genetic information into mainstream medicine to improve healthcare for billions of people.

To learn more, visitinvitae.com and follow for updates onTwitter,Instagram,Facebook andLinkedIn @Invitae.

Safe Harbor Statement

This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, including statements relating to the company's beliefs regarding the new study findings; the company's beliefs that the new study demonstrates the utility of ctDNA, MRD assays and the company's PCM technology; the company's plans with respect to its PCM technology; and the company's belief that the study results validate the need for products like PCM. Forward-looking statements are subject to risks and uncertainties that could cause actual results to differ materially, and reported results should not be considered as an indication of future performance. These risks and uncertainties include, but are not limited to:  the impact of inflation and the current economic environment on the company's business; the company's ability to grow its business in a cost-efficient manner; the company's history of losses; the company's ability to maintain important customer relationships; the company's ability to compete; the company's need to scale its infrastructure in advance of demand for its tests and to increase demand for its tests; the risk that the company may not obtain or maintain sufficient levels of reimbursement for its tests; the applicability of clinical results to actual outcomes; risks associated with litigation; the company's ability to use rapidly changing genetic data to interpret test results accurately and consistently; security breaches, loss of data and other disruptions; laws and regulations applicable to the company's business; and the other risks set forth in the company's filings with the Securities and Exchange Commission, including the risks set forth in the company's Annual Report on Form 10-K for the year ended December 31, 2022. These forward-looking statements speak only as of the date hereof, and Invitae Corporation disclaims any obligation to update these forward-looking statements.

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