Shanghai, China, Dec, 9th, 2022 - Shanghai Henlius Biotech, Inc. (2696.HK) announced that the first patient has been dosed in the phase 1 clinical trial (NCT05394168) of the company’s HLX53, an anti-TIGIT Fc fusion protein, for the treatment of advanced or metastatic solid tumors or lymphomas in China. At present, there is no Fc fusion protein anti-TIGIT has been approved for marketing globally.
T-cell immunoreceptor with immunoglobulin and ITIM domains (TIGIT) has emerged as popular inhibitory checkpoint receptor, which is mainly expressed on natural killer (NK) cells, activated CD8+ T and CD4+ T cells, and T regulatory cells. TIGIT binds to the ligand CD155 (poliovirus receptor, PVR), mainly expressed on antigen-presenting cells (APC) or the surface of tumour cells, to down-regulate T cell and NK cell functions[1-2]. As an immune checkpoint protein, TIGIT can inhibit innate and adaptive responses in various mechanisms of action and act as “brakes” like PD-1/PD-L1 does to stop T cells from attacking tumours[3]. Studies have shown that TIGIT inhibitor are effective against lung cancer, gastric cancer, melanoma, multiple myeloma, etc. HLX53 is an anti-TIGIT Fc fusion protein independently developed by Henlius, consisting of variable domain of heavy chain of heavy-chain antibody (VHH) and wildtype IgG1 Fc. Pre-clinical studies have demonstrated that HLX53 exhibits excellent tumor inhibition[4] with good safety.
Underpinned by the patient-centric strategy, Henlius has built an innovative product pipeline with many emerging targets, including PD-1/L1, LAG-3, TIGIT, BRAF, etc. The company has also independently developed HLX301, a recombinant humanized anti-PDL1 and anti-TIGIT bispecific antibody (BsAb), in patients with advanced tumours. Currently, the first patient has been dosed in Australia in Phase 1 clinical trial of HLX301 and the IND application has been approved in China for the treatment of advanced tumors. Ahead of the same class of BsAb targeting PD-L1×TIGIT, HLX301 is potentially to be the first-in-class anti-PD-L1×TIGIT BsAb. Looking forward, Henlius will continue conducting clinical studies for more innovative products in bispecific antibodies and the antibody-drug conjugates (ADC) and exploring combination therapies with improved efficacy to provide patients with quality and affordable biologics.
About NCT05394168
This open-label, dose-escalation, first-in-human, phase 1 study aims to evaluate the safety, tolerability, pharmacokinetics and preliminary efficacy of HLX53 in patients with advanced or metastatic solid tumours or lymphomas who have no standard therapy or failed the standard therapy. The study will follow an accelerated titration design (ATD) in combination with “3+3” design. Eligible subjects will be given different doses of HLX53 (QW: 30, 150, 400, 800 mg; Q2W: 1600 mg; Q3W: 2400 mg) intravenously. The primary endpoints of this study are the adverse event profile, as well as the dose-limiting toxicity (DLT), maximum tolerated dose (MTD), and recommended phase 2 dose (RP2D) of HLX53. Secondary endpoints include pharmacokinetic parameters, pharmacodynamic characteristics, immunogenicity, and efficacy.
Reference
[1] Chauvin JM, Zarour HM. TIGIT in cancer immunotherapy. J Immunother Cancer. 2020;8(2).
[2] Sanchez-Correa B, Valhondo I, Hassouneh F, et al. DNAM-1 and the TIGIT/PVRIG/TACTILE Axis: Novel Immune Checkpoints for Natural Killer Cell-Based Cancer Immunotherapy. Cancers (Basel). 2019;11(6):877.
[3] Yue C, Gao S, Li S, Xing Z, Qian H, Hu Y, Wang W and Hua C (2022) TIGIT as a Promising Therapeutic Target in Autoimmune Diseases. Front. Immunol. 13:911919.
[4] Botong Hua, Ming Yang, Jie Xue, Chen Dong, Yi-Ting Mao, Ou Li, Eric Cheung, Hassan Issafras, Wenfeng Xu, Weidong Jiang; Abstract 2451: A novel single domain antibody targeting TIGIT for cancer use in combination therapies. Cancer Res 1 July 2021; 81 (13_Supplement): 2451.