753P - Unlocking the circulating immune landscape of advanced clear-cell ovarian cancer: Insights from the MOCCA trial

Background

Clear-cell ovarian cancer (CCOC) is an aggressive ovarian cancer subtype known for its chemoresistance and poor prognosis. While PD-(L)1 inhibitors represent a promising therapeutic strategy in CCOC, the MOCCA trial, a randomized phase 2 study comparing durvalumab (D) to physician’s choice chemotherapy (PCC) in recurrent CCOC, failed to demonstrate a survival benefit with immunotherapy. This report aims to correlate the peripheral immune profile with outcomes to identify potential predictive biomarkers of immunotherapy benefit.

Methods

47 patients (pts) were enrolled in the MOCCA trial, 31 received D and 16 PCC. Blood specimens were prospectively collected before D/PCC for immune profiling of leukocyte subsets and soluble factors. Flow cytometry analysis with 25 markers was performed on Day 7 blood stabilized in Cyto-Chex® BCT and acquired in BD FACSymphony A5 cell analyzer. Cell phenotypes were assessed with lineage markers post debris and antibody non-specificity removal. Plasma cytokine and chemokine concentrations were measured by bead-based multiplex assay (Milliplex) with Luminex Flexmap3D system.

Results

35 blood samples were collected at baseline, 23 in the D arm and 12 in the PCC arm. Pts with a longer progression-free survival (PFS) (>12 weeks) exhibited significantly higher levels of circulating CD3⁺ T-cells (p=0.01), CD4⁺ T-cells (p=0.02), CD19⁺ B-cells (p=0.048) and NK-cells (p=0.02), along with lower levels of neutrophils (p=0.009), compared to pts with <12w PFS. Additionally, pts with longer PFS to D showed significantly elevated baseline levels of CCL11 (p<0.001), CCL15 (p=0.009) and CCL2 (p=0.011) compared to those with shorter PFS. Conversely, no differences in the circulating immune profile were observed between pts treated with PCC who had >16w PFS vs <16w PFS, although circulating VEGF levels were significantly higher in pts with longer PFS (p=0.012).

Conclusions

In the MOCCA trial, patients with a favorable response to immunotherapy exhibited increased levels of circulating T-cells, B-cells, NK-cells, and specific cytokines along with decreased neutrophil levels. These circulating immune markers may serve as predictive tools for optimizing the use of immune-checkpoint inhibitors in CCOC.

Clinical trial identification

NCT03405454.

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

AstraZeneca.

Disclosure

F. Blanc-Durand: Financial Interests, Personal, Invited Speaker: Eisai; Financial Interests, Personal, Member of Board of Directors: Cureety; Financial Interests, Institutional, Research Grant: AZ; Other, Travel: GSK. V.Y.M. Heong: Financial Interests, Institutional, Advisory Board: AstraZeneca, Novartis, MSD, DKSH, Gilead sciences; Financial Interests, Institutional, Invited Speaker: AstraZeneca, Gilead sciences; Non-Financial Interests, Principal Investigator: Gilead Sciences, Celgene; Non-Financial Interests, Other, co-investigator: Daichi Sankyo, Pfizer; Non-Financial Interests, Other, Co-I: AstraZeneca; Non-Financial Interests, Advisory Role: Amoy DX; Non-Financial Interests, Member: American Society of Clinical Oncology, Academy of Medicine, Singapore. D.S. Tan: Financial Interests, Personal, Invited Speaker: AstraZeneca, MSD, Merck Serono, Roche, Eisai, GSK, Takeda; Financial Interests, Personal, Advisory Board: AstraZeneca, Bayer, MSD, Eisai, Roche, Genmab, GSK, Boehringer Ingelheim; Financial Interests, Personal, Stocks/Shares: Asian Microbiome Library (AMiLi); Financial Interests, Institutional, Research Grant: Roche, Bayer, Karyopharm Therapeutics, AstraZeneca; Financial Interests, Institutional, Coordinating PI: AstraZeneca, Bergen Bio; Financial Interests, Institutional, Local PI: Zeria Pharmaceutical Co Ltd, Bayer, Byondis B.V.; Non-Financial Interests, Leadership Role, Ex society president: Gynecologic Cancer Group Singapore; Non-Financial Interests, Member of Board of Directors: Gynaecologic Cancer Intergroup (GCIG); Non-Financial Interests, Leadership Role, Ex- Chair: Asia-Pacific Gynecologic Oncology Trials Group (APGOT); Non-Financial Interests, Institutional, Product Samples, Research Study: MSD, Eisai, AstraZeneca, Cyclacel Pharmaceuticals. All other authors have declared no conflicts of interest.