Development of a PD-L1 immunohistochemistry (IHC) assay for use as a companion diagnostic for pembrolizumab (MK-3475) in non-small cell lung cancer (NSCLC).

Dolled‐Filhart, Marisa; Roach, Charlotte; Toland, Grant; Musser, Jeanette; Lubiniecki, Gregory M.; Ponto, Gary; Emancipator, Kenneth

doi:10.1200/jco.2015.33.15_suppl.11065

Cited by 9 publications

(6 citation statements)

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“…16 The optimal cutoff was TPS ≥50% for the PD-L1 IHC 22C3 pharmDx assay. 17 After the cutoff was determined, clinical outcome data and PD-L1 expression results from another set of 61 previously treated patients were used to analyze the correlation of clinical outcome with PD-L1 status with TPS ≥50%. The treatment effect of pembrolizumab in the 61 previously treated subjects who had a tumor PD-L1 of TPS ≥50% was substantial, with an overall response rate of 41% (95% CI, 28.6-54.3) as compared with 20.6% (95% CI, 15.5-26.5) observed in the 223 subjects irrespective of PD-L1 status (Table 1 ).…”

Section: Resultsmentioning

confidence: 99%

Development of a Companion Diagnostic PD-L1 Immunohistochemistry Assay for Pembrolizumab Therapy in Non–Small-cell Lung Cancer

Roach

Zhang²,

Corigliano³

et al. 2016

Applied Immunohistochemistry &Amp; Molecular Morphology

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A companion diagnostic assay was codeveloped by Dako for pembrolizumab non–small-cell lung cancer clinical trials to detect PD-L1 expression by immunohistochemistry (IHC). This automated IHC assay has been analytically verified and validated using Dako’s autostainer Link 48 and 22C3 mouse anti-PD-L1 monoclonal antibody to detect the PD-L1 expression in formalin-fixed paraffin-embedded human tumor tissue specimens. The PD-L1 22C3 IHC assay was optimized for high sensitivity and specificity. Repeatability and reproducibility studies were conducted at Dako and at 3 Clinical Laboratory Improvement Amendments certified laboratories during assay development. The studies included: intersite and intrasite, interobserver and intraobserver, interinstrument, interoperator, interday, and interlot, and intraday and intrarun. All precision studies performed at Dako and external laboratories achieved >85% point-estimate agreements for all 3 agreement types (negative, positive, and overall). A clinical cutoff (tumor proportion score ≥50%) of PD-L1 expression was determined and evaluated through a phase 1 clinical trial (KEYNOTE-001) for advanced non–small-cell lung cancer patients treated with pembrolizumab. The treatment effect of pembrolizumab in the 61 subjects who had a tumor PD-L1 of tumor proportion score ≥50% was substantial, with an overall response rate of 41% (95% confidence interval, 28.6-54.3) as compared with 20.6% (95% confidence interval, 15.5-26.5) observed in the 223 subjects irrespective of PD-L1 status. PD-L1 IHC 22C3 pharmDx is a sensitive, precise, and robust companion diagnostic assay, which will facilitate safe and effective use for pembrolizumab in cancer patients.

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Section: Resultsmentioning

confidence: 99%

Development of a Companion Diagnostic PD-L1 Immunohistochemistry Assay for Pembrolizumab Therapy in Non–Small-cell Lung Cancer

Roach

Zhang²,

Corigliano³

et al. 2016

Applied Immunohistochemistry &Amp; Molecular Morphology

Self Cite

283

228

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“…It is important to note that each PD-L1 IHC assay used in this study was developed in the context of a specific clinical program as a complete system solution including a primary antibody clone, detection reagents, a staining platform, and a software protocol. 21,29,30 Scoring and interpretation guidelines were developed to identify responding populations for unique drugs and biologic hypotheses. By virtue of their use in clinical trials, these assays have each been validated by a correlation with patient outcome after being analytically validated as required by the FDA through the premarket application approval process.…”

Section: Discussionmentioning

confidence: 99%

PD-L1 Immunohistochemistry Assays for Lung Cancer: Results from Phase 1 of the Blueprint PD-L1 IHC Assay Comparison Project

Hirsch

McElhinny

Stanforth

et al. 2017

Journal of Thoracic Oncology

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The Blueprint PD-L1 IHC Assay Comparison Project revealed that three of the four assays were closely aligned on tumor cell staining whereas the fourth showed consistently fewer tumor cells stained. All of the assays demonstrated immune cell staining, but with greater variability than with tumor cell staining. By comparing assays and cutoffs, the study indicated that despite similar analytical performance of PD-L1 expression for three assays, interchanging assays and cutoffs would lead to "misclassification" of PD-L1 status for some patients. More data are required to inform on the use of alternative staining assays upon which to read different specific therapy-related PD-L1 cutoffs.

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“…Formalin-fixed paraffin embedded tumor tissues were deparaffinized and dehydrated in xylene and graded ethanol solutions. PD-L1 expressions were scored according to a tumor proportion score, which was defined as the percentage of tumor cells with complete or partial membranous staining at any intensity 15 , 16 . Representative images of IHC staining for PD-L1 are illustrated in Appendix 1.…”

Section: Methodsmentioning

confidence: 99%

Associations of Tumor PD-1 Ligands, Immunohistochemical Studies, and Textural Features in 18F-FDG PET in Squamous Cell Carcinoma of the Head and Neck

Chen

Lin

Shen

et al. 2018

Sci Rep

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To know tumor PD-L1 expression through IHC or the FDG-PET related radiomics, we investigated the association between programmed cell death protein 1 ligand (PD-L1) expression and immunohistochemical (IHC) biomarkers or textural features of 18F-fluoro-2-deoxdeoxyglucose positron emission tomography (18F-FDG PET) in 53 oropharyngeal or hypopharyngeal cancer patients who were ready to undergo radiotherapy-based treatment. Differences in textural features or biomarkers between tumors with and without PD-L1 expression were tested using a Mann–Whitney U test. The predicted values for PD-L1 expression were examined using logistic regression analysis. The mean percentages of tumor PD-L1 expression were 6.2 ± 13.5. Eighteen tumors had PD-L1 expression ≥5%, whereas 30 tumors ≥1%. Using a 5% cutoff, the p16 staining percentage and the textural index of correlation were two factors associated with PD-L1 expression. The odds ratios (ORs) were 17.00 (p = 0.028) and 0.009 (p = 0.015), respectively. When dichotomizing PD-L1 at 1%, the p16 and Ki-67 staining percentages were two predictors for PD-L1 expression with ORs of 11.41 (p = 0.035) and 757.77 (p = 0.045). p16 and Ki-67 staining percentages and several PET/CT-derived textural features can provide supplemental information to determine tumor PD-L1 expression in HNCs.

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Development of a PD-L1 immunohistochemistry (IHC) assay for use as a companion diagnostic for pembrolizumab (MK-3475) in non-small cell lung cancer (NSCLC).

Cited by 9 publications

References 0 publications

Development of a Companion Diagnostic PD-L1 Immunohistochemistry Assay for Pembrolizumab Therapy in Non–Small-cell Lung Cancer

Development of a Companion Diagnostic PD-L1 Immunohistochemistry Assay for Pembrolizumab Therapy in Non–Small-cell Lung Cancer

PD-L1 Immunohistochemistry Assays for Lung Cancer: Results from Phase 1 of the Blueprint PD-L1 IHC Assay Comparison Project

Associations of Tumor PD-1 Ligands, Immunohistochemical Studies, and Textural Features in 18F-FDG PET in Squamous Cell Carcinoma of the Head and Neck

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