KEY TAKEAWAYS
- The Phase 1 trial aimed to investigate the PD-L1 expression determination in CRC, specifically focusing on PD-L1 IHC 22C3 pharmDx at the CPS ≥ 1 cutoff.
- Researchers noticed robust external lab reproducibility of PD-L1 IHC 22C3 pharmDx for PD-L1 expression in CRC at the CPS ≥ 1 cutoff.
Despite advances in colorectal carcinoma (CRC) care, it remains a major global cause of cancer-related deaths. Recent MK4280–001 results demonstrated clinical efficacy for anti-LAG3 antibody with favezelimab plus pembrolizumab in patients with microsatellite stable metastatic CRC with PD-L1 with a Combined Positive Score (CPS) ≥ 1.
Lining Hutchinson and her team aimed to assess the external reproducibility, providing evidence for PD-L1 expression determination in CRC using PD-L1 IHC 22C3 pharmDx at CPS ≥ 1 cutoff.
The study performed an inclusive analysis at a three-site, blinded, and randomized reproducibility investigation of PD-L1 IHC 22C3 pharmDx on formalin-fixed paraffin-embedded human CRC specimens. Endpoints included inter-site, intra-site/inter-day, inter-observer, and intra-observer reproducibility at CPS ≥ 1 cutoff. For inter-site and intra-site reproducibility, five replicate sets of pre-qualified unstained specimens underwent staining and evaluation at each of the three testing sites. Inter-observer and intra-observer reproducibility were assessed using one pre-stained specimen set, evaluated three times at each testing site.
Analytical agreements of diagnostic outcomes (positive/negative) were statistically analyzed, determining negative percent agreement (NPA), positive percent agreement (PPA), and overall percent agreement (OA). Pre-determined acceptance criteria mandated a lower bound of at least 85.0% for the two-sided 95% CI on NPA, PPA, and OA for all reproducibility endpoints.
All CPS ≥ 1 cutoff endpoints for CRC met the criteria. Inter- and intra-site reproducibility had 95% CI LB values of 98.7% NPA, 96.0% PPA, and 98.0% OA. Inter- and intra-observer reproducibility achieved 98.9% NPA, 98.6% PPA, and 99.4% OA, confirming PD-L1 IHC 22C3 pharmDx’s consistent and reliable performance in clinical assessments.
The study concluded with robust evidence affirming high external lab reproducibility of PD-L1 IHC 22C3 pharmDx concerning PD-L1 expression in CRC at the CPS ≥ 1 cutoff. These findings underscore the reliability of PD-L1 assessment, supporting its valuable role in clinical applications for CRC.
The study is sponsored by Merck Sharp & Dohme LLC
Source: https://jitc.bmj.com/content/11/Suppl_1/A3
Clinical Trial: https://clinicaltrials.gov/study/NCT02720068
Hutchinson L, Bahadori A, Kalpakoff M, et al. (2023). “3 External reproducibility of PD-L1 IHC 22C3 pharmDx for colorectal carcinoma specimens at CPS ≥ 1 cutoff.” Presented at SITC 2023 (Abstract ).
