A phase 1 first-in-human clinical trial of HMBD-002, an IgG4 monoclonal antibody targeting VISTA, in advanced solid tumors.

作者：Jordi Rodon Ahnert, Joshua James Gruber, Melinda L. Telli, Monica M Mita, Alain C. Mita, Joseph W. Kim, Miguel Angel Villalona-Calero, Meera Patel, Shalini Singh Yadav, Padmanee Sharma, Tom Haber, Jessica Symons, Qihui Seet, Bhushan Dharmadhikari, Dipti Thakkar, Kon Yew Kwek, Leah N. DiMascio, Eric Keith Rowinsky, Piers J. Ingram, Jerome Douglas Boyd-Kirkup · 发表于：Journal of Clinical Oncology · 年份：2023 · DOI：10.1200/jco.2023.41.16_suppl.tps2664 · 被引用次数：12 · 研究领域：Peptidase Inhibition and Analysis、Cancer Immunotherapy and Biomarkers、Monoclonal and Polyclonal Antibodies Research

TPS2664 Background: V-domain Ig Suppressor of T-cell Activation (VISTA), is an immune checkpoint regulator found on tumor, myeloid, and other immune cells. Its presence has been shown to enhance tumor growth, create an immunosuppressive microenvironment, and may potentially contribute to developing resistance to anti-CTLA-4 and anti-PD-1/PD-L1 therapies. Therefore, VISTA represents a promising therapeutic target. HMBD-002, a non-depleting, high-affinity IgG4 monoclonal antibody against VISTA, has demonstrated significant inhibition of tumor growth in preclinical studies, both as a monotherapy and in combination with pembrolizumab. HMBD-002 acts by increasing T-cell activity and reprogramming the suppressive tumor microenvironment to a proinflammatory antitumor phenotype. Cancer types including triple-negative breast cancer (TNBC) and non-small cell lung cancer (NSCLC), which exhibit high expression levels of VISTA in the TME, provide a rational basis for exploring these indications in clinical studies. Methods: This phase 1/2, open-label, multi-center trial is being conducted in two parts to evaluate the safety, pharmacokinetics, and antitumor activity of HMBD-002, an IgG4 monoclonal antibody targeting VISTA, as a monotherapy and in combination with pembrolizumab. The dose-escalation stage (Part 1) will follow a standard 3 + 3 study design with weekly dosing and adaptive dose-escalation increments to determine the recommended phase 2 dose (RP2D) for subsequent disease-directe...