64O - Clinical validation of a tissue-agnostic genome-wide methylome enrichment assay for MRD in head and neck cancers

Background

Outcomes for patients with locally advanced head and neck cancer (HNC) remain disappointing, with 5-year overall survival rates at 50%. Curative treatment involves surgery, radiation therapy, and/or combined chemotherapy. Approximately 80%-90% of all recurrences occur within the first 2 years after completion of treatment; Personalized treatment decisions based on patients identified with molecular residual disease (MRD) could contribute to improved outcomes.

Methods

Patients with TNM 8th Ed. stage I-IVB HNC (n=325) including n=125 stage I-III human papillomavirus (HPV)-positive oropharynx cancer were prospectively enrolled at diagnosis, and peripheral blood plasma was collected longitudinally at diagnosis, and approximately 3,12, and 24 months after curative intent treatment. The full cohort includes 325 unique patients with 1,155 samples. Samples were split into distinct sets to train and test a classifier capable of identifying and measuring cfDNA cancer signal using differentially methylated regions. 5-10 ng of cfDNA isolated from each plasma sample was used for cfMeDIP-seq.

Results

In the training cohort, a total of 326 post-treatment samples from 140 unique patients [stage I 45 (32%), II 22 (16%), III 30 (21%), IV 43 (31%)] were analyzed and correlated with recurrence free survival (RFS). At the landmark timepoint, patients who tested positive showed significantly worse RFS than those who tested negative (Hazard ratio (HR) 9.18; 95% CI, 4.54 to 18.58, P<0.001). Incorporating serial longitudinal samples, RFS was worse in patients who tested positive compared to those that tested negative (HR 9.97; 95% CI, 4.11 to 24.14, P<0.001). Patients that had positive cfDNA cancer signal recurred significantly more often than the patients that did not have cfDNA cancer signal after curative intent treatment.

Conclusions

These data demonstrate that MRD detection with a tissue-agnostic, genome-wide methylome enrichment platform in HNC patients after curative intent treatment correlates strongly with RFS. The assay can provide relative detection of cfDNA cancer signal which can be used to direct therapy and monitor for recurrence. An analysis from the held-out clinical validation cohort will be presented at the meeting.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.

Funding

Adela, Inc.

Disclosure

G. Liu: Financial Interests, Personal, Advisory Board: AstraZeneca, Takeda, Novartis, Lilly, Pfizer, Merck, EMD Serono; Financial Interests, Personal, Research Grant: AstraZeneca, Takeda. B. Brown, J.T. Jones, Y. Wang: Financial Interests, Personal, Full or part-time Employment: Adela, Inc.; Financial Interests, Personal, Stocks/Shares: Adela, Inc. C. Melton: Financial Interests, Personal, Full or part-time Employment: Adela, Inc..; Financial Interests, Personal, Stocks/Shares: Adela, Inc., Grail, Inc. J. Bergener: Financial Interests, Personal, Full or part-time Employment: Adela, Inc.; Financial Interests, Personal, Stocks/Shares: Adela, Inc., Adela, Inc. J. Zhang: Financial Interests, Personal, Full or part-time Employment: Adela, Inc; Financial Interests, Personal, Stocks/Shares: Adela, Inc. O. Hall, J. Min, S.Y. Shen, J. Provance, E. Sosa, A. Licon, J. Zhang: Financial Interests, Personal, Full or part-time Employment: Adela, Inc.; Financial Interests, Personal, Stocks/Shares: Adela, Inc. B. Allen: Financial Interests, Personal, Full or part-time Employment: Adela, Inc; Financial Interests, Personal, Stocks/Shares: Adela, Inc, Grail. A. Hartman: Non-Financial Interests, Personal, Officer: Adela, Inc; Financial Interests, Personal, Full or part-time Employment: Adela, Inc; Financial Interests, Personal, Ownership Interest: Adela, Inc. D. De Carvalho: Non-Financial Interests, Personal, Officer: Adela, Inc; Financial Interests, Personal, Full or part-time Employment: Adela, Inc; Financial Interests, Personal, Ownership Interest: Adela, Inc.; Non-Financial Interests, Institutional, Other, Patents associated with cfMeDIP-seq technology: Adela, Inc. All other authors have declared no conflicts of interest.