Abstract CT010: A phase II study of durvalumab and tremelimumab with front-line neoadjuvant chemotherapy in patients with advanced-stage ovarian cancer (KGOG 3046/TRU-D)
Authors: Park Junsik , Park Eunhyang , Joung Je-Gun , Lim Myong Cheol , Kim Byoung-Gie , Kim Jae Weon , Lee Jung Bok , Kim Sunghoon , Choi Chel Hun , Kim Hee Seung , Park Sang Yoon , Chung Jongsuk , Lee Jung-Yun 
Published: June 2022

Abstract
KGOG 3046 is a single-arm phase 2 study evaluating the combination of dual immune checkpoint inhibition (durvalumab [D] and tremelimumab [T]) with neoadjuvant chemotherapy (NAC) for the upfront advanced-stage epithelial ovarian cancer (aEOC). This study enrolled patients with FIGO stage IIIC-IV EOC. Patients were assigned to one of the following neoadjuvant chemo-immunotherapy (NACI): original cohort arm1 (D 1,500 mg q3w + T 75 mg q3w + paclitaxel 175 mg/m2 + carboplatin AUC 5 [3 cycles]) or expansion cohort arm2 (D 1,500 mg q3w + T 300 mg [1 dose] + same chemotherapy as original). Arm2 was initiated after the completion of arm1. After NAC, all patients underwent interval debulking surgery (IDS). After IDS, three cycles of D (1,120 mg) and adjuvant chemotherapy followed by D maintenance (1,120 mg [total 12 cycles]) were administered. During treatment, serial biopsies were performed to explore immunologic changes in tumor microenvironment (TME). The primary endpoint was a 12-month PFS rate. Interim analysis was performed to evaluate outcomes after NAC after all patients underwent IDS. A total of 45 patients were enrolled as follows: arm1 (n=23) and arm2 (n=22). The majority of the patients presented with high-grade serous carcinoma (91.1%) and stage IV disease (77.8%). After NAC, the ORR was 86.7% by RECIST v1.1 (95.7% in arm1 and 81.8% in arm2, P=0.17). At IDS, 30 patients (66.7%) had R0 resection (73.9% in arm1 and 59.1% in arm2, P=0.353). Fourteen patients (31.1%) had a CRS 3 (39.1% in arm1 and 22.7% in arm2, P=0.337) and 5 (11.1%) had a pathologic remission. Skin rashes were the most common adverse events (51.1%) and grade ≥3 events occurred in 3 patients (15.6%), which completely resolved after steroid use. Stromal TIL (P=0.0335), CD8 (P&lt;0.001), CD8/Foxp3 ratio (P&lt;0.001) on immunohistochemistry were significantly increased after NACI. When TILs were analyzed in detail by flow cytometry, suppressive intratumoral regulatory T cells (Treg) were significantly decreased after NACI in both arm (P&lt;0.05). Interestingly, the frequency of intratumoral Treg after NACI was lower in arm1 than arm2 (P&lt;0.05). These interim data highlight the clinical activity and manageable toxicity profile for the addition of D and T to NAC in aEOC. Additional translational study data will be presented at the meeting.
Summary of secondary outcomes D+T75+CT (n=23) D+T300+CT (n=22) P value ORR by RECIST 22 (95.7%) 18 (81.8%) 0.187 ORR by PERCIST 13/14a (92.9%) 16/18a (88.9%) 0.856 R0 at IDS 17 (73.9%) 13 (59.1%) 0.353 CRS3 at IDS 9 (39.1%) 5 (22.7%) 0.337 Pathologic CR 4 (17.4%) 1 (4.5%) 0.348 a, PERCIST was available in 14 (original) and 18 (expansion) cohorts.
Citation Format: Junsik Park, Eunhyang Park, Je-Gun Joung, Myong Cheol Lim, Byoung-Gie Kim, Jae Weon Kim, Jung Bok Lee, Sunghoon Kim, Chel Hun Choi, Hee Seung Kim, Sang Yoon Park, Jongsuk Chung, Jung-Yun Lee. A phase II study of durvalumab and tremelimumab with front-line neoadjuvant chemotherapy in patients with advanced-stage ovarian cancer (KGOG 3046/TRU-D) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr CT010.