Assessing a Novel Predictive Marker of Immune Checkpoint Response in Head and Neck Cancer

A novel predictive digital pathology biomarker of immune checkpoint blockers (ICB) demonstrates high predictive response power in first-line head and neck cancers (HNC), according to a study presented at the European Society for Medical Oncology (ESMO) Congress 2024.

Investigators analyzed 26 cases of patients with metastatic HNC treated with first-line PD-1 inhibitors, all with CPS>1%. They then utilized their ENLIGHT-DP pipeline to generate, in a blinded manner, individual response scores to PD-1 inhibition for tissue sample slides. They noted that ENLIGHT-DP has two main steps: prediction of mRNA expression directly from an H&E slide using DeepPT, their digital-pathology based algorithm; and use of these values as input to ENLIGHT, their transcriptome-based precision oncology platform.

The findings showed that the ENLIGHT-DP score had an overall response rate of ROC AUC ¼ 0.65. The researchers noted that using a predefined threshold for binary classification of response derived from independent data, six of eight patients that were predicted to respond by ENLIGHT-DP responded (75% PPV, 43% sensitivity, Odds Ratio of 3.75). In comparison, stratification by CPS exhibits no predictive power (PPV of 50% and 58%, respectively, for CPS >20% and CPS 1-19%, and AUC of 0.46 for CPS as a continuous score), the researchers noted.

“ENLIGHT-DP demonstrates high predictive power for response to ICB in first-line HNC, outperforming the commonly used CPS marker. Importantly, our approach does not require training on prior treatment outcomes, and can therefore be generalized to drugs for which such data is unavailable or scarce,” the researchers concluded.

Reference

Bentebibel SE, McGrail D, Wahab R. Clinical and biomarker analyses of intratumoral CD40 agonist sotigalimab in combination with pembrolizumab in metastatic melanoma: A phase I/II trial. Abstract #71MO. Presented at the European Society for Medical Oncology Congress 2024; September 13-17, 2024; Barcelona, Spain.