Shanghai, China, January 27th, 2022-Shanghai Henlius Biotech, Inc. (2696.HK) today announced that the first patient has been dosed in the Phase 2 clinical trial of HLX208 for the treatment of adult Langerhans cell histiocytosis (LCH) and Erdheim-Chester disease (ECD) with BRAF V600E mutation. HLX208 is a small-molecule inhibitor licensed from NeuPharma that targets the human BRAF protein V600E mutation.
BRAF is a member of the RAF kinase family and a critical upstream regulator in the RAS-RAF-MEK-ERK mitogen-activated protein kinase (MAPK) cell signaling pathway. Its mutation can activate the downstream MEK and ERK protein, which induces the proliferation and invasion of tumour cells[1]. Among all BRAF mutation types, BRAF V600E mutation is the most common one. According to the 2019 edition of the Clinical Practice Guidelines for Rare Diseases issued by the National Health Commission of China, LCH and ECD are driven by constitutive activation of the MAPK/ERK signaling pathway with more than 50% incidence of BRAF V600E mutation. Currently, except for a BRAF V600E inhibitor approved for ECD in the United States, no similar therapy is approved for the treatment of LCH and ECD globally, implying that many patients with BRAF V600E mutant have unmet medical needs.
HLX208 is a potential “best-in-class” BRAF inhibitor with a proprietary novel chemical structure that is different from other marketed BRAF inhibitors. It exhibited a single crystal morph, high bioavailability, and excellent anti-tumour efficacy in preclinical studies. Subsequent early clinical data also demonstrated preliminary efficacy and good safety and tolerability in patients with cancer, warranting further clinical development. This single-arm, open-label, multi-centre, phase 2 study aims to evaluate the efficacy, safety and pharmacokinetic profiles of HLX208 in adult patients with BRAF V600E mutation Langerhans Cell Histiocytosis (LCH) and Erdheim-Chester disease (ECD). The primary objective of this study is to evaluate the efficacy of HLX208 in BRAR V600E-mutated patients with the two rare diseases mentioned above. The primary endpoint is objective response rate (ORR) assessed by independent review committee (IRC) per PERCIST v1.0. The secondary endpoints include ORR assessed by investigators per PERCIST v1.0, ORR assessed by IRC and investigators per RECIST v1.1, disease control rate (DCR), 1-year progress-free survival rate (1-year PFSR), 1-year overall survival rate (1-year OSR), safety and pharmacokinetic characteristics, etc.
Putting unmet clinical needs as the first priority, Henlius has built a diversified product pipeline in monoclonal antibodies, bispecific antibodies, and the antibody-drug conjugates (ADC). Looking forward, Henlius will continue its momentum for innovation, further strengthening the in-licensing and collaboration on external innovative assets and bringing more high-quality and affordable therapies to patients worldwide.
Reference
[1] Huang Z, Wu Y. Huang Z, Wu Y. Mutation of the BRAF genes in non-small cell lung cancer. Zhongguo Fei Ai Za Zhi. 2012;15(3):183-186.