EON: Phase II trial of etigilimab (MPH313) in combination with nivolumab in patients with recurrent platinum-resistant clear cell ovarian cancer.

Abstract

5573 Background: A predictor of response to anti-PD1 therapy is the extent of CD8+ infiltration within the pretreated tumor. TIGIT has shown to suppress anti-tumor immune responses via increased CD4+ Tregs and disruption of CD226 co-stimulation. We hypothesized inhibition of TIGIT may reverse the immune suppressive tumor microenvironment thereby potentiating the efficacy of PD-1 blockade in ovarian cancer. We sought to explore toxicity and efficacy of the combination of TIGIT inhibitor, etigilimab, and PD-L1 inhibitor, nivolumab. Methods: Eligible patients (pts) had platinum-resistant recurrent clear cell ovarian cancer with no prior immunotherapy and unlimited prior lines. Measurable disease and adequate end organ function were required. Pts received etigilimab 1000mg IV and nivolumab 240mg IV every 2 weeks. Bayesian optimal phase 2 design was used to conduct the trial. Dual primary end points were toxicity assessment by CTCAE v5.0 and objective response per modified RECIST v1.1. Clinical benefit (CBR) was defined as objective response or stable disease (SD) for >/= 4 months. Progression-free survival was defined as time from first treatment to documented disease progression. NCT05715216. Results: 23 pts received at least one cycle of treatment. Median age was 54 years (range 38-73); 65.2% of pts were Non-Hispanic white, 17.4% Hispanic, 8.7% Black and 8.7% Asian. Median lines of prior therapy was 2 (range 0-8). No patient received prior PARP inhibitor. Grade 3 or 4 adverse events were observed in 47.8% of pts, the most common of which was abnormal liver function tests. Other common adverse events of any grade included nausea/vomiting (34.8%), fatigue (30.4%), and anemia (30.4%). Of 20 pts evaluable for response, objective response rate was 15.0% (95% CI 3.2-37.9%) with 1 complete response (CR) and 2 partial responses (PR). CBR was 30.0% (95% CI 11.9%-54.3%). Median duration of response was 8.6 months, with ongoing responses in 2 pts at 20.0 and 8.6 months. Median duration of clinical benefit was 7.5 months. Single-cell RNA seq analysis of tumor tissues from 9 pts (CR/PR=2, SD=4, PD=3) revealed immunologic changes in the tumor microenvironment after treatment. Notably, an increased frequency of plasma B cells (p=0.02) was associated with clinical response. Conclusions: The combination of etigilimab and nivolumab was well tolerated. Promising clinical response and duration of benefit was observed in a heavily pretreated population of pts with clear cell ovarian cancer. Our data highlight a potential role of B cells in clinical response. Further analysis on the association of benefit by molecular features is ongoing. Clinical trial information: NCT05715216 .