Background: Despite advances in cancer care and detection, more than 65% of patients with squamous cell cancer of the head and neck (HNSCC) will develop recurrent and/or metastatic disease. The prognosis for these patients is poor with a 5 year overall survival of 39%. Recent treatment advances in immunotherapy, including immune checkpoint inhibitors like pembrolizumab and nivolumab, have resulted in clinical benefit in a subset of patients. There is a critical clinical need to identify patients who benefit from these anti-PD-1 immune checkpoint inhibitors. Methods: Here we report findings from a multi-center observational study, PREDAPT (ClinicalTrials.gov: NCT04510129), conducted across 17 US healthcare systems. PREDAPT aimed to validate OncoPrism-HNSCC, a clinical biomarker assay predictive of disease control in recurrent or metastatic HNSCC patients treated with anti-PD-1 immune checkpoint inhibitors as a single agent (monotherapy) and in combination with chemotherapy (chemo-immunotherapy). The test used RNA-sequencing data and machine learning models to score each patient and place them into groups of Low, Medium, or High. Results: The OncoPrism-HNSCC prediction significantly correlated with disease control in both the monotherapy cohort (n=62, p=0.004) and the chemo-immunotherapy cohort (n=50, p=0.01). OncoPrism-HNSCC also significantly predicted progression-free survival in both cohorts (p=0.015 and p=0.037, respectively). OncoPrism-HNSCC had more than threefold higher specificity than PD-L1 combined positive score and nearly fourfold higher sensitivity than tumor mutational burden for predicting disease control. Conclusions: Here we demonstrate the clinical validity of the OncoPrism-HNSCC assay in identifying patients with disease control in response to anti-PD-1 immune checkpoint inhibitors.

KCF, JE, JH, RLW, MMP, DNM, JIG, and EJD are employed, have stock interests, and/or a financial relationship with Cofactor Genomics, Inc., maker of the OncoPrism-HSNCC test.

https://clinicaltrials.gov/study/NCT04510129

This study was wholly funded by Cofactor Genomics, Inc.

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

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The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

IRB of WCG (20201975) and Advarra (Pro00051202) gave ethical approval for this work.

I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.

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I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

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I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.

Yes

The data underlying this study, including anonymized patient-level OncoPrism-HNSCC, PD-L1, and TMB measurements, are available for non-commercial use from the corresponding author upon reasonable request.