2022-RA-968-ESGO Immunotherapy response monitoring using personalized circulating tumor DNA analysis in patients with relapsed gynecologic malignancies

Abstract

2022-RA-945-ESGO Table 1 Methodology GARNET (NCT02715284) is a phase 1, multicentre, open-label, single-arm study of dostarlimab in patients with advanced/recurrent solid tumours. Three expansion cohorts enrolled patients based on MMR status: dMMR (A1) and MMRp (A2) advanced/recurrent EC, and dMMR non-EC solid tumours (F). Patients received dostarlimab 500 mg IV Q3W for 4 cycles, then 1000 mg IV Q6W until progression or discontinuation. TMB and PDL1 were exploratory biomarkers. TMB status was determined by FoundationOne test; TMB-high (TMB-H) was defined as 10 mutations/Mb. PDL1 expression was determined by combined positive score (CPS) by Ventana assay; PDL1-high (PDL1-H) was defined as CPS 1. The study was not powered to assess antitumour activity within subgroups. Results TMB-H and PDL1-H were common in dMMR solid tumours; PDL1-H was observed in 39.4% of MMRp EC tumours (table 1). Objective response rate (ORR) was higher in patients with TMB-H/PDL1-H tumours (55.6% for all cohorts, combined; Table). Safety for each cohort was previously reported. Conclusion PDL1-H and TMB-H were frequently observed in the dMMR EC and non-EC cohorts, regardless of tumour type; PDL1-H was also prevalent in MMRp EC tumours. Although not a powered analysis, ORR by BICR per RECIST v1.1 was higher in patients with TMB-H and PDL1-H solid tumours. Across cohorts, dMMR status was predictive of response. REFERENCE 1. Andre T, et al. Ann Oncol 2021;32(suppl 5):S829-S866. 991P. 2022-RA-968-ESGO IMMUNOTHERAPY RESPONSE MONITORING USING PERSONALIZED CIRCULATING TUMOR DNA ANALYSIS IN PATIENTS WITH RELAPSED GYNECOLOGIC MALIGNANCIES Kayla Castaneda, Jose Salvador Saldivar, Young Kwang Chae, Hemant Sindhu, Concepcion Diaz-Arrastia, Kassondra Grzankowski, Georges Azzi, Carly Bess Scalise, Ekaterina Kalashnikova, Brittany Nicosia, Shilpa Tekula, Alexey Aleshin, Adam C ElNaggar. Spero Women’s Oncology Center, El Paso, TX; Northwestern University Feinberg School of Medicine, Chicago, IL; Southwest Cancer Care, Sierra Vista, AZ; Memorial Hermann, Houston, TX; Austin Cancer Center, Austin, TX; Holy Cross Health, Ft. Lauderdale, FL; Natera, Inc., Austin, TX 10.1136/ijgc-2022-ESGO.879 Introduction/Background Immunotherapy has transformed cancer care. Unfortunately, responses within gynecologic malignancies have been modest when compared to other disease sites. Biomarkers for early determination of treatment benefit are urgently needed to spare unnecessary toxicity and cost. We evaluated if circulating tumor DNA (ctDNA) dynamics enable early detection of progressive disease (PD) and treatment response in patients with recurrent, gynecologic malignancies receiving immunotherapy. Methodology Longitudinal plasma samples (n=138) were collected from 25 patients with recurrent cervical (N=6), endometrial (N=12), or ovarian (N=7) cancers who received immunotherapy. A personalized, tumor-informed multiplex PCR assay (Signatera bespoke mPCR NGS assay) was used for the detection of ctDNA in plasma samples. Results Pre-treatment samples were available for 9 patients (78% ctDNA detection rate) and all 25 patients had on-treatment samples (68% ctDNA detection rate). Serially ctDNA negative patients (3/15 with imaging) had no evidence of disease on-treatment. ctDNA clearance was observed in 3 (cervical, N=2; endometrial, N=1) of the remaining 12 patients and correlated with clinical benefit. ctDNA decreased in additional 2 patients, both with objective response, while all 7 patients with increased ctDNA had PD. Increased ctDNA Abstracts A410 Int J Gynecol Cancer 2022;32(Suppl 2):A1–A504 on D ecem er 2, 2022 by gest. P rocted by coright. http/ijgc.bm jcom / nt J G ynecol C acer: frst pulished as 10.11ijgc-2022-E S G O .79 on 20 O cber 222. D ow nladed fom predicted PD prior to imaging by an average of ~2.5 months (lead-time) and was significantly associated with worse progression-free survival (PFS) compared to patients with decreased ctDNA (HR=0.14, 95%CI: 0.03–0.60; p<0.01). TMB and MSI status (binary) were not predictive of response in univariate (p=0.4, p=0.4) analyses. Conclusion ctDNA dynamics can accurately predict clinical benefit and allow for early prediction of PD in patients with advanced ovarian cancer receiving immunotherapy. Further study is warranted to evaluate the clinical utility of a personalized, tumor-informed ctDNA assay in patients with gynecologic malignancies undergoing systemic therapies. 2022-RA-1007-ESGO HIGH EXPRESSION OF FAP+ CANCERASSOCIATED FIBROBLASTS PREDICT POOR OUTCOME IN PATIENTS WITH HIGH-GRADE SEROUS OVARIAN CANCER WITH HIGH CD8-POSTIVE T-CELL INFILTRATION Josefin Fernebro, Sara Corvigno, Arthur Mezheieusky, Josefin Severin Karlsson, Laura Martin De La Fuente, Sofia M Westbom-Fremer, Joseph Carlson, Paivi M Kannisto, Ingrid M Hedenfalk, Susanne M Malander, Arne Östman, Hanna Dahlstrand. Medical Unit Pelvic Cancer, Theme Cancer, Karolinska University Hospital, Stockholm, Sweden; Department of Oncology-Pathology, Stockholm, Sweden; Department of Pathology and Cytology, Stockholm, Sweden; Division of Oncology and Pathology, Department of Clinical Sciences, lund, Sweden; Department of Obstetrics and Gynecology, Lund, Sweden; Medical Unit Pelvic Cancer, Theme Cancer, Stockholm, Sweden 10.1136/ijgc-2022-ESGO.880 Introduction/Background Tumor biology studies have implied that fibroblasts act as negative regulators of immune cell function in cancer. We investigated the impact of FAP-positive cells in high-grade serous ovarian cancer (HGSC) in relation to CD8 expression. Methodology A discovery cohort (N=113) of HGSC was subjected to immunohistochemistry (IHC) of FAP and CD8. Marker status was correlated with overall survival (OS) and progression-free survival (PFS). Findings were confirmed in a validation cohort (N=121) and in public available datasets (TCGA and GSE9891). Results We confirmed previous findings that high density of CD8+ cells in HGSC is associated with longer OS compared to low density (HR 0.55; 95% CI 0.33–0.85; p=0.008). In the discovery cohort high intensity of FAP was associated with shorter median PFS in cases with high density of stromal CD8+ cells (11.4 versus 18.6 months) compared to low intensity of FAP (p=0.007). In contrast, high intensity of FAP was not associated with PFS in cases with low density of CD8+ cells. In the validation cohort, high intensity of FAP in the patients with high density of stromal CD8+ cells was associated with shorter OS compared to low intensity of FAP (p=0.01). This association was not seen in the cases with low density of CD8+ cells. The association between high FAP expression and poor outcome in the high density CD8+ group was confirmed in two independent gene-expression data sets, with a shorter PFS in the TCGA dataset and shorter PFS and OS in the GSE9891 dataset. Conclusion The study shows a specific FAP positive fibroblastsubset of cases with poor prognosis restricted to a CD8 high density group of HGSC. Therapy targeting the immunosuppressive action of fibroblasts may be a tool to enhance the known positive prognostic effect of CD8-cells in ovarian cancer and may be explored in T-cell depended immune therapy. 2022-RA-1093-ESGO VALIDATION OF SELF-SAMPLING USE FOR A MULTIPLEXED BIOMARKER ASSAY FOR HPV AND DYSPLASIA DETECTION Anna Sophie Skof, Eva-Maria Payrich, Maja Struck, Sarah Thies, Carola Schreckenberger, Jalid Sehouli, Andreas M Kaufmann. Klinik für Gynäkologie, Charité – Universitätsmedizin Berlin – corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin,