Scoring methods for anti-PD therapy eligibility and compositions for performing same
Aspects of the present disclosure provide methods for determining the eligibility of a subject having a malignancy for treatment with an anti-PD therapeutic agent based on a Combined Positive Score (CPS) for a tumor tissue sample from the subject. Compositions and kits or performing the disclosed methods are also provided.
1. A method for determining the eligibility of a subject having a malignancy for treatment with an anti-PD therapeutic agent known to have an anti-PD-1/PD-L1 therapeutic effect, the method comprising:
determining the number of viable PD-L1 positive tumor cells, the number of viable PD-L1 negative tumor cells, and the number of viable PD-L1 positive mononuclear inflammatory cells (MIC) in a tumor tissue sample from a subject having a malignancy; and
calculating a combined positive score (CPS) for the tumor tissue sample using the formula:
C
P
S
=
PD
-
L
1
positive
tumor
cells
+
PD
-
L
1
positive
MIC
PD
-
L
1
positive
tumor
cells
+
PD
-
L
1
negative
tumor
cells
×
100
%
wherein the subject is eligible for treatment with said anti-PD therapeutic agent known to have an anti-PD-1/PD-L1 therapeutic effect when the CPS is above a threshold.
2. The method of claim 1 , wherein the threshold is from about 10% to about 1%.
3. The method of claim 1 , wherein the threshold is 1%.
4. The method of claim 1 , wherein the tumor tissue sample is a tissue section of a tumor biopsy.
5. The method of claim 4 , wherein PD-L1 is detected by immunohistochemistry (IHC) staining.
6. The method of claim 4 , wherein the tumor tissue section is a formalin fixed and embedded in paraffin wax (FFPE) tumor tissue section.
7. The method of claim 4 , wherein the tissue section is stained.
8. The method of claim 7 , wherein the stain comprises a hematoxylin and eosin (H&E) stain.
9. The method of claim 4 , wherein the viable PD-L1 positive tumor cells, the number of viable PD-L1 negative tumor cells, and the number of viable PD-L1 positive MIC are counted in the tumor nests and the adjacent supporting stroma of the tumor tissue sample.
10. The method of claim 1 , wherein the tumor tissue sample comprises a cell suspension.
11. The method of claim 10 , wherein the number of viable PD-L1 positive tumor cells, the number of viable PD-L1 negative tumor cells, and the number of viable PD-L1 positive MIC in the tumor tissue sample are determining by flow cytometry.
12. The method of claim 1 , wherein one or more additional markers are detected in the tumor tissue sample.
13. The method of claim 12 , wherein the marker is specific for MIC or is selected from the group consisting of: CD3, CD5, CD4, CD7, CD8, and CD20.
14. The method of claim 1 , wherein the method further comprises, prior to the determining step, contacting the tumor tissue sample with an anti-PD-L1 antibody or a binding fragment thereof.
15. The method of claim 1 , wherein the number of viable PD-L1 positive tumor cells, the number of viable PD-L1 negative tumor cells, or the number of viable PD-L1 positive MIC in the tumor tissue sample are determined by single cell sequencing.
16. The method of claim 1 , wherein the malignancy is selected from the group consisting of: gastric cancer, head and neck cancer, renal cell carcinoma, urothelial/bladder carcinoma, ovarian carcinoma, myeloma, melanoma, lung cancer, squamous cell carcinoma, classical Hodgkin's lymphoma, breast cancer, triple negative breast cancer, hormone receptor positive (ER and/or PR) and Her2 positive breast cancer, small cell lung cancer, salivary gland carcinoma, vulvar carcinoma, thyroid carcinoma, anal canal carcinoma, biliary carcinoma, mesothelioma, cervical carcinoma, and neuroendocrine carcinoma.
17. The method of claim 1 , wherein the anti-PD therapeutic agent inhibits an anti-cell death activity of PD-1/PD-L1.
18. The method of claim 1 , wherein the anti-PD therapeutic agent comprises an anti-PD or an anti-PD-L1 specific antibody or a binding fragment thereof.
19. The method of claim 1 , wherein the anti-PD therapeutic agent is selected from the group consisting of: Avelumab, Nivolumab, Pembrolizumab, BMS-936559, MPDL3280A, Pidilizumab, and MEDI4736.
20. The method of claim 1 , wherein the anti-PD therapeutic agent is Pembrolizumab and wherein one or more additional markers are detected in the tumor tissue sample, and wherein said one or more additional markers comprise CD3.