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, 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
M
I
C
total
number
of
viable
tumor
cells
×
100
%
wherein the subject is eligible for treatment with said anti-PD therapeutic agent when the CPS is above a threshold from 60 to 1.
2. The method of claim 1 , wherein the threshold is 1.
3. The method of claim 1 , wherein the tumor tissue sample is a tissue section of a tumor biopsy.
4. The method of claim 3 , wherein PD-L1 is detected by immunohistochemistry (IHC) staining.
5. The method of claim 3 , wherein the tumor tissue section is a formalin fixed and embedded in paraffin wax (FFPE) tumor tissue section.
6. The method of claim 3 , wherein the tissue section is stained.
7. The method of claim 3 , further comprising staining a section from the biopsy with a hematoxylin and eosin (H&E) stain.
8. The method of claim 3 , wherein the viable PD-L1 positive tumor cells, the total number of viable 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.
9. The method of claim 1 wherein the number of PD-L1 positive tumor cells and the number of PD-L1 positive MIC are determined using an anti-PD-L1 antibody or a PD-L1 binding fragment thereof.
10. 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.
11. 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.
12. The method of claim 1 further comprising administering the anti-PD therapeutic agent to the subject when the CPS is above the threshold.
13. The method of claim 1 , wherein the anti-PD therapeutic agent is Pembrolizumab.
14. The method of claim 13 , wherein the malignancy is non-small cell lung carcinoma.
15. The method of claim 1 , further comprising administering Pembrolizumab to the subject when the CPS is above the threshold.
16. The method of claim 13 , wherein the malignancy is esophageal carcinoma.
17. The method of claim 1 , wherein the threshold is 10.
18. The method of claim 13 wherein the malignancy is gastric carcinoma.
19. The method of claim 13 wherein the malignancy is cervical carcinoma.
20. The method of claim 13 wherein the malignancy is urothelial carcinoma.
21. The method of claim 13 wherein the malignancy is head and neck carcinoma.
22. The method of claim 1 , wherein the threshold is 20.