Background 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.

Methods A modified ‘3+3’ 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.

Results 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.

Conclusions YBL-006 showed favorable safety profiles. Although the number of enrolled pts was not large, preliminary efficacy data showed similar treatment outcomes compared to currently available anti-PD-1/PD-L1 antibodies. Interestingly, anti-tumor efficacy was also observed in grade 3 NET/NEC.

Y-biologics Inc would like to thank all the participating patients, dedicated clinical trial investigators and their team members who have helped to bring this novel therapy to the clinic. This research was supported by Korea Drug Development Fund funded by Ministry of Science and ICT, Ministry of Trade, Industry, and Energy, and Ministry of Health and Welfare (HN21C1391, Republic of Korea).

Trial Registration NCT04450901

Ethics Approval This study obtained ethics approvals at the following ethics/IRB’s;

Seoul National University Hospital IRB: H-2003–032-1109

Seoul National University budnag hospital IRB: B-2005/615–402

Severance Hospital Yonsei University Health System IRB: 4–2021-0912

Asan Medical Center IRB: 2021–1111

Samsung medical center IRB: 2021–06-213

Macquarie University IRB: 52020631615298

King Chulalongkorn Memorial Hospital IRB: 693/63

Participants gave informed consent before taking part.