Abstract Background: Butyrophilin 1A1 (BTN1A1) is a novel immune checkpoint that is found to be mutually exclusive with PD-(L)1. BTN1A1 has the potential to broaden the range of immunotherapeutic treatments available for patients who are currently unresponsive to anti-PD-(L)1 therapy. In this phase, 1 clinical trial, the safety and preliminary efficacy of Nelmastobart (hSTC81), a humanized monoclonal antibody targeting BTN1A1, was evaluated in patients with advanced solid tumors. Methods: This is a first-in-human, phase 1, dose-escalation study evaluating Nelmastobart in pts with advanced solid tumors. Primary objectives are to characterize the safety profile and determine the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D). Nelmastobart is administered as monotherapy at increasing dose levels of 0.3, 1, 3, 6, 10, and 15 mg/kg on a Q2W schedule. Results: As of June 30, 2023, 45 pts are enrolled at dose levels of 0.3 (n=1), 1 (n=9), 3 (n=10), 6 (n=9), 10 (n=9), and 15 mg/kg (n=8). Of note, 3 pts with ovarian cancer at dose levels of 6 (n=1), 10 (n=1), 15 mg/kg (n=1), and 1 pt with thymic cancer at the dose level of 6 mg/kg (n=1) were enrolled. A maximum administered dose of 15 mg/kg was achieved; no DLTs were observed at any dose level. Focusing on the ovarian/thymic cancer subgroup, 2 pts are ongoing: 1 pt with ovarian cancer (10 mg/kg) and 1 pt with thymic cancer (6 mg/kg). The median duration of therapy was 20 weeks (maximum 33 weeks). Only 1 pt with ovarian cancer (6 mg/kg) reported any treatment-related adverse events (TRAE), including grade 1 headache, nausea, myalgia, and decreased appetite. In the evaluable pts, two confirmed stable diseases are observed in thymic cancer (6 mg/kg) and ovarian cancer (10 mg/kg). The median duration of SD pts is 29 weeks. Preliminary pharmacokinetic (PK) analysis revealed consistent exposure with linear PK. Pharmacodynamic analysis measuring cytokines and cell-based markers is pending and will be shared. Conclusion: Nelmastobart demonstrates excellent tolerability without any DLTs up to the highest administered dose of 15 mg/kg. The available data show promising signs of anti-tumor activity, along with sustained stable disease. Currently, clinical development planning for a phase Ib/II clinical trial is underway, aiming to investigate the optimal therapeutic dose and efficacy of Nelmastobart in multiple types of solid tumors. Citation Format: Stephen Yoo, Soohyeon Lee, Sangjoon Shin, Particia LoRusso, Jiwon Hur, Hyunjin Jung, David S Hong. Update on the phase 1 trial of Nelmastobart in patients with advanced solid tumors [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2023 Oct 11-15; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2023;22(12 Suppl):Abstract nr C066.