Available Assays

 

Companion vs complementary diagnostic assays

 

FDA-approved IVD assays for PD-L1 testing may be indicated as companion or complementary assays.1,2

 

  • Are required for use with a specific therapy
  • Provide essential information for the safe and effective use of a corresponding drug or biological product
  • Can identify patients who are most likely to benefit from a specific therapeutic agent
  • Must be noted in the prescribing information of therapies requiring the use of an FDA-approved test
  • Identify patients to be at increased risk for serious side effects as a result of treatment
  • Are not required for use with a specific therapy
  • Provide information that may assist physicians when deciding which patients may benefit most from treatment
Companion IVD assays2,3
  • Are required for use with a specific therapy
  • Provide essential information for the safe and effective use of a corresponding drug or biological product
  • Can identify patients who are most likely to benefit from a specific therapeutic agent
  • Must be noted in the prescribing information of therapies requiring the use of an FDA-approved test
  • Identify patients to be at increased risk for serious side effects as a result of treatment
Complementary IVD assays1,4
  • Are not required for use with a specific therapy
  • Provide information that may assist physicians when deciding which patients may benefit most from treatment

Commercially available assays

 

Multiple diagnostic assays are commercially available, each with different scoring cutoffs to detect PD-L1 expression.5-8

 

Commercially available assays for PD-L1 testing

Commercially available assays for PD-L1 testing

  Ventana PD-L1 (SP263)5,9,10 Ventana PD-L1 (SP142)6 Dako PD-L1 IHC 22C3 pharmDx7, * Dako PD-L1 IHC 28-8 pharmDx8,†
  • Cutoff for high PD-L1 expression
  • TC ≥25%
  • or
  • ICP >1%, IC ≥25%
  • or
  • ICP=1%, IC=100%
  • IC ≥5%
  • CPS ≥10% 
  • TC ≥1% 
  • TC ≥5% 
  • Approval status
  • FDA-approved complementary diagnostic for UC
  • FDA-approved companion diagnostic for UC
  • FDA-approved companion diagnostic for UC
  • Under clinical investigation for UC

Ventana PD-L1

(SP263)5,9,10

Ventana PD-L1

(SP142)6

  • Cutoff for high PD-L1 expression

TC ≥25%

or

ICP >1%, IC ≥25%

or

ICP=1%, IC=100%

  • IC ≥5%
  • Approval status

FDA-approved complementary

diagnostic for UC

FDA-approved companion

diagnostic for UC

Dako PD-L1 IHC 22C3 pharmDx7, * Dako PD-L1 IHC 28-8 pharmDx8,†
  • Cutoff for high PD-L1 expression
  • CPS ≥10%

TC ≥1%

TC ≥5%

  • Approval status
  • FDA-approved companion diagnostic for UC
  • Under clinical investigation for UC

*CPS is defined as the percentage of PD-L1–positive TCs and ICs relative to the total number of tumor cells. A CPS cutoff of ≥10% is currently being studied in UC as the definition of PD-L1 high expression.
FDA approved for detecting PD-L1 expression in NSCLC and melanoma tissues.10

 

See the product label for more information on proper use of FDA-approved companion diagnostics.

 

 

Laboratory-developed tests

 

LDTs were developed and their performance characteristics determined by specific institutions in a manner consistent with the Clinical Laboratory Improvement Amendments of 1988 (CLIA) requirements.11,12,‡

Sample requirements vary for each LDT. Always verify that your samples adhere to the individual test specifications.11,12

These tests are performed in laboratories that adhere to performance specifications established by the Clinical Laboratory Improvement Amendments of 1988 (CLIA) under the regulation of the Centers for Medicare & Medicaid Services. They are not FDA approved.

 

 

Scoring Assays

 

Scoring for PD-L1 assays differs; therefore, familiarity with assay requirements can ensure accurate interpretation of test results.5,6,9,10

 

Scoring cutoffs for PD-L1 diagnostic assays in urothelial carcinoma
Scoring cutoffs for PD-L1 diagnostic assays in urothelial carcinoma

Determine PD-L1 status using the PD-L1 CPS, defined as the percentage of PD-L1–expressing TCs and tumor-infiltrating ICs relative to the total number of TCs.7

 

Dako 22C3 assay scoring criteria
Dako 22C3 assay scoring criteria

Determine PD-L1 status by the percentage of PD-L1–expressing TCs with positive membrane staining at any intensity relative to the total number of TCs.8

 

Dako 28-8 assay scoring criteria
Dako 28-8 assay scoring criteria

PD-L1 expression is not binary; it is expressed across a continuum.15

PD-L1 expression is not binary; it is expressed across a continuum.15

 

 

CPS, combined positive score; FDA, Food and Drug Administration; IC, immune cell; ICP, immune cells present; IHC, immunohistochemistry; IVD, in vitro diagnostic; LDT, laboratory-developed test; NSCLC, non–small cell lung cancer; PD-L1, programmed death-ligand 1; TC, tumor cell; UC, urothelial carcinoma.

 

References: 1. Mansfield E. http://www.personalizedmedicinecoalition.org/Userfiles/PMC-Corporate/file/Mansfield-Presentation-Dec-PCM.pdf. Accessed March 15, 2018. 2. Food and Drug Administration (FDA). http://www.fda.gov/MedicalDevices/ProductsandMedicalProcedures/InVitroDiagnostics/ucm301431.htm. Updated December 28, 2017. Accessed March 13, 2018. 3. FDA. http://www.fda.gov/MedicalDevices/ProductsandMedicalProcedures/InVitroDiagnostics/ucm407297.htm. Updated January 23, 2018. Accessed March 13, 2018. 4. FDA. https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm501762.htm. Published May 16, 2016. Accessed March 13, 2018. 5. Ventana PD-L1 (SP263) Assay [package insert]. Tucson, AZ: Ventana Medical Systems, Inc; 2018. 6. Ventana PD-L1 Assay (SP142) [package insert]. Tucson, AZ: Ventana Medical Systems, Inc; 2018. 7. Bellmunt J et al; KEYNOTE-045 Investigators. N Engl J Med. 2017;376(11):1015-1026. 8. Sharma P et al. Lancet Oncol. 2017;18(3):312-322. 9. Dako PD-L1 IHC 22C3 pharmDx [interpretation manual]. Carpinteria, CA: Dako North America Inc; 2015. 10. Dako PD-L1 IHC 28-8 pharmDx [product information]. Carpinteria, CA: Dako North America Inc; 2015. 11. FDA. http://www.fda.gov/MedicalDevices/ProductsandMedicalProcedures/InVitroDiagnostics/ucm407296.htm. Updated February 4, 2018. Accessed March 13, 2018. 12. Fitzgibbons PL et al; College of American Pathologists Pathology and Laboratory Quality Center. Arch Pathol Lab Med. 2014;138(11):1432-1443. 13. Massard C et al. J Clin Oncol. 2016;34(26):3119-3125. 14. Powles T et al. Nature. 2014;515(7528):558-562. 15. Patel SP, Kurzrock R. Mol Cancer Ther. 2015;14(4):847-856.