KEY FINDINGS: • IO therapy was associated with a median OS benefit of > 2 years.• We did not identify any prognostic markers of IO-therapy response.• MSI-H and TMB-H are rare in USC, but PD-L1 is present in nearly

20% of cases. • Notably these markers did trended toward a survival benefit, which

could have important clinical implications. Further study is warranted.

Immune-response markers and actual response to immune-oncology therapy in uterine serous carcinoma.

NL Jones1, S Wu2, J Xiu2, A Craig3, G Smaldone3, E Hernandez3, RP Rocconi1, J Brown4, T Herzog5, R Holloway6, WM Korn2, M Powell7, AM Wilhite1

1University of South Alabama, Mobile, AL 2Caris Life Sciences, Phoenix, AZ 3Temple University, Philadelphia, PA 4Atrium Health, Charlotte, NC 6University of Cincinnati, Cincinnati, OH 6 AdventHealth Cancer Institute, Orlando, FL 7Washington University, St. Louis, MO

Results: Figure 4: Immune microenvironment characterized by immune-cell fraction.

1000 3000 4000 50000Time, days

1.0

0.8

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0.2

0.0

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e pr

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Figure 2: Treatment with IO therapy in USC had a significantly improved median overall survival benefit of more than 28 months. A

• Uterine serous carcinoma (USC) is an aggressive type of endometrial cancer with poor prognosis and limited treatment options.

• Immune-oncology (IO) agents have shown promise USC, though data is limited regarding which patients benefit most from IO therapy.

• In other malignancies, PD-L1, MSI-H status and high TMB have been predictive of IO response.

Median OS 59.6 vs 31.2 months; HR(95% CI):

0.38(0.24-0.61) p <0.001

c

characterize the immune profiles of USC and investigate treatment response to IO therapy

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Figure 5: Patients with IO therapy response markers trended toward a better median survival, but this was not significant; A. MSI-H (OS not yet reached vs 31.6 months; HR(95% CI): 0.69(0.38-1.25) , B. TMB-H (months: 36.4 vs 31.6; HR(95% CI): 0.84(0.50-1.39). C. PD-L1 (months: 34.4 vs 31.2; HR(95% CI): 0.90 (0.74-1.1),

A

B

Objective:

Background:

2000 6000

USC with IO therapy (n=92)USC without IO therapy (n=2306)

0%5%

10%15%20%25%

% A

ltere

d

TMB-H PD-L1MSI-H

Figure 3: Markers of response to IO therapy. Serous tumors were low in microsatellite instability and tumor mutation burden. Nearly 20% expressed PD-L1.

4.2%

19.1%

2.3%

Immune CellB cell 4.71%

Macrophage M1 1.35%Macrophage M2 5.35%

Monocyte 0.00%Neutrophil 2.10%

NK cell 2.94%T cell CD4+ (non-regulatory) 0.00%

T cell CD8+ 0.12%T cell regulatory (Tregs) 1.59%

Myeloid dendritic cell 3.45%uncharacterized cell 74.78%

B ce

ll

Mac

roph

age

M1

Mac

roph

age

M2

Mon

ocyt

e

Neu

troph

il

NK

cell

T ce

ll C

D 4

+

T ce

ll C

D8+

T re

g

mye

loid

den

driti

c

50%

40%

30%

20%

10%

0%

1.0

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0.6

0.4

0.2

0.0

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t fre

e pr

opor

tion

2000 4000 60000Time, days

1000 2000 3000 40000Time, days

1.0

0.8

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0.4

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e pr

opor

tion

MSI-H (n=43)

MSS (n=1463)

TMB high (n=43)

TMB low (n=807)

PD-L1 pos (n=308)

PD-L1 neg (n=1543)

C

- Statistical significance determined by chi-square and Wilcoxon rank sum test.

- p values adjusted for multiple comparisons (q) to be <0.05

- Survival calculated using CodeAI data

CODEai insurance claims data

2806 USC tumors

NextGen DNA sequencing

RNA sequencing

Immunohisto-chemistry

Comprehensive tumor profiling (Caris

Life Sciences)

Methods:

Analysis

Figure 1: Flowchart describing methods