Keun-Wook Lee, John J. Park, Seung Tae Kim, Virote Sriuranpong, Sun Young Rha, Changhoon Yoo, Sehyun Kim, Bhumsuk Keam, Dhanusha Sabanathan, Joon Oh Park, Napa Parinyanitikul, Min Hwan Kim, Kyu-Pyo Kim, Chan-Young Ock, Jaebong Yoon, Hyelim Lim, Sangheon Lee, Wooick Jang, Do-Youn Oh<\/p>\n
SITC, 2023<\/strong><\/p>\n Background<\/strong> YBL-006 is a novel human monoclonal antibody against programmed cell death 1 (PD-1). A first-in-human study was conducted to evaluate the safety, the recommended phase 2 dose, and anti-tumor efficacy. We have previously presented interim results, here we present the updated safety and efficacy results based on the data at the end of the study.<\/p>\n Methods<\/strong> A modified \u20183+3\u2019 design was utilized for the dose escalation (cohort A; CA) of 0.5, 2, 5, and 10 mg\/kg. In the dose expansion (cohort B; CB), 200 mg every 2 weeks and 300 mg every 3 weeks were administered. Overall response rate (ORR) was evaluated per RECIST v1.1. Adverse events (AEs) were graded according to the CTCAE v5.0. For the exploratory biomarker analysis, tumor-infiltrating lymphocytes (TIL) analysis from H&E slides was conducted using Lunit SCOPE IO (an artificial intelligence-powered whole-slide image analyzer). Tumor mutational burden-high (TMB-H) and microsatellite instability-high (MSI-H) were also evaluated.<\/p>\n Results<\/strong> 10 (CA) and 56 (CB) patients (pts) were included in the safety population and 10 (CA) and 53 (CB) in the efficacy population. In the CA, 1 patient (penile squamous cell carcinoma) experienced complete response (CR), 1 patient (anal squamous cell carcinoma) partial response (PR), and 3 pts stable disease (SD), with ORR 20%, disease control rate (DCR) 50%, and median progression-free survival (PFS) 4.5 months. In the CB, 1 patient (gastric cancer [GC]) experienced CR, 7 pts PR (neuroendocrine tumor\/carcinoma [NET\/NEC; N=2], GC [N=2], kidney cancer [N=1], nasopharyngeal cancer [N=1] and hurthle cell thyroid carcinoma [N=1]), and 21 pts SD with ORR 15.1%, DCR 54.7%, median duration of response 11.0 months and median PFS 2.8 months. The most reported treatment-related AEs were fatigue (N=3) and pruritus (N=2) in CA; fatigue (N=11), pruritis (N=7), and rash (N=5) in CB. In the overall efficacy population (both CA and CB), 50 pts were evaluated for TIL, and the ORR for the inflamed immune phenotype (IIP) was 38.5% (5\/13 pts), which was higher than the Non-IIP (13.5% [5\/37 pts]). Two (2)\/8 pts (25%) with TMB-H (both with GC) had CR and PR, respectively, and they were also MSI-H cases. Among 8 pts with grade 3 NET\/NEC, two had PR and they were not MSI-H or TMB-H cases.<\/p>\n