Abstract CT147: A phase II study of neoadjuvant immune checkpoint inhibitor IMC-001 (anti-PD-L1 antibody) in patients with resectable upper gastrointestinal cancers (Neo-Chance Study)
Authors: Park Sook Ryun , Song Joon Seon , Song In Hye , Yoo Moon-Won , Kim Yong-Hee , Kim Hyeong Ryul , Shim Ju Hyun , Lee Danbi , Choi Jonggi , Song Ki Won 
Published: April 2023

Abstract
Background: Immune checkpoint inhibitors have shown survival benefits in unresectable/metastatic gastric cancer (GC), esophageal cancer (EC), and hepatocellular carcinoma (HCC). Based on scientific rationale for neoadjuvant immunotherapy, we conducted a phase II study of neoadjuvant IMC-001, a novel PD-L1 targeting fully human monoclonal antibody, for resectable GC, EC, and HCC.
Methods: This is a prospective, phase II study of neoadjuvant IMC-001 (20 mg/kg iv every 2 weeks for 2 cycles) across three cohorts of resectable GC, EC, and HCC. The primary endpoint is major pathologic response rate (&lt;10% of viable tumor cells) and secondary endpoints include safety, feasibility, R0 resection rate, tumor response rate, progression-free survival, relapse-free survival, and overall survival. Exploratory endpoints include immune monitoring and biomarker analysis in tumor tissues, peripheral blood, and stool.
Results: From Sep. 2019 to Nov. 2022, 50 patients (pts) were enrolled and treated (safety analysis population), and among them, 48 pts were evaluable for the efficacy analysis (16 HCC; 16 GC; 16 EC); male (81%), median age=62 yrs (range, 39-77), and clinical stage (AJCC 8th ed.) I (56%)/II (33%)/III (10%). All tumors were microsatellite stable and 33% of tumors were PD-L1+. 45 pts (94%) completed 2 cycles of neoadjuvant IMC-001, all pts underwent surgery, and only one pt’s surgery was delayed due to immune-related hepatitis. No pts had disease progression during neoadjuvant therapy, and among the 17 pts with measurable lesion(s) by RECIST 1.1, 3 pts (18%) showed partial response (PR) and 14 pts (82%) had stable disease (SD). Among 30 metabolic response-evaluable pts by EORTC criteria, 7 pts (15%) showed metabolic PR, 20 pts (43%) had metabolic SD, and 3 pts (6%) had metabolic PD. Among 2 of 3 pts with metabolic PD, surgical pathology showed increased tumor infiltrating lymphocytes and tumor regression. The median change of the sum of SUVmax was -13% (range, -76% to 59%). All pts underwent R0 resection with pathologic stage of I (75%)/II (13%)/III (13%). Although there was no major pathologic response, 51% of pts showed various degree of tumor necrosis or fibrosis and 7 pts (15%) had residual viable tumor cells less than 50%. Except for grade 3 AST/ALT elevation (6%), all treatment-related adverse events (TRAEs) were grade 1 or 2. TRAEs occurring in ≥5% of pts were hyperthyroidism (18%), hypothyroidism (14%), fatigue (14%), pruritus (12%), skin rash (8%), infusion-related reaction (6%), and diarrhea (6%).
Conclusions: Neoadjuvant IMC-001 was well tolerated and demonstrated antitumor activity in microsatellite stable, resectable GC, EC, and HCC pts. The updated clinical and biomarker results will be presented.
Citation Format: Sook Ryun Park, Joon Seon Song, In Hye Song, Moon-Won Yoo, Yong-Hee Kim, Hyeong Ryul Kim, Ju Hyun Shim, Danbi Lee, Jonggi Choi, Ki Won Song. A phase II study of neoadjuvant immune checkpoint inhibitor IMC-001 (anti-PD-L1 antibody) in patients with resectable upper gastrointestinal cancers (Neo-Chance Study) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr CT147.