Abstract
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.
Highlights
The ability of tumor cells to bypass the immune system’s natural process of detecting and destroying malignancies is a key point of interest in the realm of immuno-oncology[1]
Analytical and clinical validation studies demonstrate that PDL1 IHC 22C3 pharmDx is a precise companion diagnostic assay, allowing for selection of eligible head and neck squamous cell carcinoma (HNSCC) patients for treatment with pembrolizumab
PD-L1 expression was observed across the dynamic range from Combined Positive Score (CPS) 0 to CPS 100 (Figures 1, 2)
Summary
The ability of tumor cells to bypass the immune system’s natural process of detecting and destroying malignancies is a key point of interest in the realm of immuno-oncology[1]. This process can be interrupted by a tumor’s potential to evade immune surveillance via T-cell checkpoint pathways, thereby thwarting an effective immune response and allowing the tumor to recur and/or metastasize[2,3]. PD-L1 and PD-L2, are often expressed on the surface of tumor cells[3,4], as well as on immune cells[6]. An increased understanding of dysregulation and evasion of the immune system via the PD-L1 pathway has resulted in improved options for immunotherapeutic intervention, significantly benefiting cancer patients who fall into relevant clinical populations
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
