Development of a Companion Diagnostic PD-L1 Immunohistochemistry Assay for Pembrolizumab Therapy in Head and Neck Squamous Cell Carcinoma

Objectives: FDA approval of PD-L1 IHC 22C3 pharmDx for use as an aid in identifying head and neck squamous cell carcinoma (HNSCC) patients for treatment with pembrolizumab was based on the results of rigorous analytical and clinical validation testing. Methods: For the HNSCC indication, the device was validated at Agilent Technologies on the performance of sensitivity and precision using the Combined Positive Score (CPS) ≥ 1 and CPS ≥ 20 cutoffs; external validation studies were performed at three external laboratories. CPS ≥ 1 and CPS ≥ 20 cutoffs were evaluated in KEYNOTE-048, a phase 3 clinical trial. Results: Analytical validation studies supporting the companion diagnostic indication (CPS ≥ 1) achieved point estimates of > 85% for negative, positive, and overall percent agreement. Clinical validation studies show that HNSCC patients treated with pembrolizumab as a single agent had an overall survival (OS) of 12.3 months at CPS ≥ 1 (95% CI, 10.8-14.9) compared with patients receiving cetuximab, platinum, and 5-fluorouracil (CPS ≥ 1 OS of 10.3 months (95% CI, 9.0-11.5)). Conclusion: Analytical and clinical validation studies demonstrate that PD-L1 IHC 22C3 pharmDx is a precise companion diagnostic assay, allowing for selection of eligible HNSCC patients for treatment with pembrolizumab.