1778P - Clear cell sarcomas (CCS) express Gp100: A novel immune target for a bispecific T cell engager

Background

CCS are rare translocation-related sarcomas (EWSR1-ATF; EWSR1-CREB1) which are often misdiagnosed as melanomas and with few active systemic treatment options. Recently, tebentafusp, a bispecific gp100 peptide-HLA-directed CD3 T cell engager, has shown to be effective in patients with uveal melanoma with a significant overall survival benefit. We investigated whether gp100 could be a potential immune target in patients with CCS.

Methods

A tissue micro-array containing 21 primary, recurrent and metastatic CCS tissue samples was stained by immunohistochemistry (IHC) for PD-L1, CD3, and gp100. PD-L1 intensity and extent were scored from 0 (none) to 3 (high). The diagnosis of CCS and IHC scoring and interpretation was made by experienced sarcoma pathologists. FISH +/- RT-PCR were used to identify the translocation and confirm the diagnosis.

Results

Of the 21 CCS samples, 13 were translocation positive, 4 were translocation-negative and 4 were not tested. In the overall cohort, the median age was 37, and 10 cases (48%) were female. The tissue of origin was metastatic, locally recurrent, and primary in 6 (30%), 3 (15%), and 11 (55%) cases. Overall, 13 (72%) of cases were gp100 positive with at least 10% expression. Translocation positive cases expressed gp100 more frequently: 11 (85%) of the translocation-positive samples and none of the translocation-negative cases expressed gp100, respectively. There was no association between gp100 expression and age, sex, or tissue of origin (primary, metastatic, recurrent). PD-L1 extent and intensity were either 0 or 1 in all cases except one. Lymphocytes (CD3+) were scant with 5 or less cells per mm² in all cases except two, both cases were translocation-positive, one case was gp100 positive and one was not.

Conclusions

Gp100 may represent a novel immune target for translocation-positive CCS. Ongoing research to investigate HLA genotyping of patients with CCS to further validate the therapeutic potential of tebentafusp in translocation-positive CCS is in progress.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.