PD-L1 IHC 28-8 pharmDx for Urothelial Carcinoma

PD-L1 IHC 28-8 pharmDx for UC

The only FDA-approved test for which PD-L1 expression in urothelial carcinoma may be associated with enhanced response rate from OPDIVO^? (nivolumab)¹

Demonstrated clinical results

Detection of PD-L1 expressing tumor cells in UC patient specimens may indicate an enhanced response rate benefit to OPDIVO (nivolumab) treatment for the patient.²

In study CHECKMATE-275, objective response rate (ORR) based on PD-L1 expression was evaluated using PD-L1 IHC 28-8 pharmDx and is summarized below. Median time to response was 1.9 months (range; 1.6-7.2).

Efficacy results for study CHECKMATE-275¹

Confirmed ORR in all patients and the two PD-L1 subgroups are summarized in the table below.

Tumor PD-L1 Expression	<1%	≥1%	All Treated Subjects
Total No. of Subjects	N=146	N=124	N=270
Confirmed Objective Response Rate No. of Subjects (95% CI)	22 (9.7, 21.9)	31 (17.7, 33.6)	53 (15.1, 24.9)
Complete Response Rate No. of Subjects (% of Total in PD-L1 expression category)	1 (0.7%)	6 (4.8%)	7 (2.6%)
Partial Response Rate No. of Subjects (% of Total in PD-L1 expression category)	21 (14.4%)	25 (20.2%)	46 (17.0%)
Median Duration of Response* Months (range)	7.6 mos. (3.7+, 12.0+)	NE (1.9+, 12.0+)	10.3 (1.9+, 12.0+)

*Estimated from the Kaplan-Meier Curve Clinical utility of PD-L1 IHC 28-8 pharmDx was evaluated in CHECKMATE-275, a phase II single arm clinical trial of nivolumab in subjects with metastatic or unresectable urothelial carcinoma or who have progressed or recurred following treatment with a platinum agent. 270 subjects were randomized to receive the drug at 63 sites in 11 countries. Major efficacy outcome measures included confirmed objective response rate (ORR) and duration of response (DOR).

Frequency of PD-L1 expression in samples from UC - CHECKMATE-275¹

Tumor PD-L1 Expression	Nivolumab (N=270)
≥1% PD-L1 Expression Subjects	124 (45.9%)
<1% PD-L1 Expression Subjects	146 (54.1%)

Baseline UC specimen origin - CHECKMATE-275¹

Non-bladder UC 27% (73/270)

Visceral metastases 84% (227/270)

• 27% of nivolumab treated patients had non-bladder urothelial carcinoma
• Regardless of tumor site, 84% of all treated patients presented with visceral metastases at baseline

Robust performance

PD-L1 IHC 28-8 pharmDx is fully validated for analytical performance, having met stringent acceptance criteria for ultimate quality results.

Selected analytical validation parameters	Results for UC
Analytical specificity	Demonstrated specificity to clone 28-8 for PD-L1 detection PD-L1 primary antibody displays no cross-reactivity for PD-L2 Detection in normal tissues restricted to immune cells and infrequently to cells of epithelial origin
Sensitivity	Broad dynamic range of PD-L1 expression (0-95% of positive tumor cells, 0-3 staining intensity) exhibited in study of 138 unique cases of human urothelial carcinoma FFPE specimen stages III to IV
Repeatability	Demonstrated lot-to-lot repeatability >91.9% overall agreement for ≥1% expression level
External reproducibility	≥87.0% overall agreement for ≥1% expression level Reproducibility testing of day-to-day, site-to-site and observer-to-observer in a blinded study in three certified clinical labs 95% confidence intervals from 77.7% to 98.2% agreement for both ANA and APA
ANA = Average Negative Agreement  |  APA = Average Positive Agreement  |  OA = Overall Agreement

Order information

Product	Code
PD-L1 IHC 28-8 pharmDx	SK005
Required but not included in kit:
Autostainer Link 48	AS480
EnVision FLEX Wash Buffer, 20x	K8007
EnVision FLEX Hematoxylin (Link)	K8008
PT Link	PT101/PT200
PT Link rinse station	PT109

References

1. Clinical Trial: CHECKMATE-275, CA209275
2. PD-L1 IHC 28-8 pharmDx Instructions for Use