Abstract CT139: A phase I study of HG146: A novel selective HDAC inhibitor, as single-agent in patients with advanced solid tumors and lymphomas

Abstract Background: Histone Deacetylase (HDAC) is a well-defined target family for cancer therapy. HG146 is an HDAC-1/IIb subtype-specific HDAC inhibitor. Compared with other marketed HDAC inhibitors, HG146 shows superior in vitro activity, resulting in potent proliferation inhibition across a wide range of both hematological as well as solid cancer cell lines. Mechanically, we found that HG146 elicited a robust suppression of c-MYC transcription. Consistent with its potent in vitro activity, HG146 significantly inhibited the growth of xenograft tumors derived from various hematological as well as solid tumor models in vivo. Method: The phase I study (NCT04977167) of HG146 utilized an accelerated dose escalation for the initial dose levels followed by a 3+3 design to determine the recommended phase 2 dose (RP2D). Safety profile and preliminary anti-tumor activity of HG146 in patients with advanced solid tumors and lymphomas were evaluated. Results: A total of 27 patients enrolled the trial and 24 patients (3 with multiple myeloma, 16 with solid tumors, and 5 with lymphomas) were evaluable for responses. Among them, 1 achieved partial response (PR), 17 had stable disease (SD), and 6 had progressive disease (PD). The longest progression-free survival from one patient with adenoid cystic carcinoma (ACC) reached 21 months and this patient is still receiving treatment. Moreover, HG146 demonstrated a good safety profile, with mostly grade 1-2 adverse events. Based on the Phase I study results, recurrent/metastatic ACC was selected for the Phase II clinical trial. Citation Format: Xiaodong Huang. A phase I study of HG146: A novel selective HDAC inhibitor, as single-agent in patients with advanced solid tumors and lymphomas [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_2):Abstract nr CT139.