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Results from the Phase 2 Clinical Trial of Henlius BRAF Inhibitor HLX208 for the Treatment of LCH and/or ECD Released at 2023 ESMO Asia


Recently, results from the phase 2 study (HLX208-LCH/ECD201) of Henlius' innovative BRAFV600E inhibitor, HLX208, in adult Langerhans cell histiocytosis (LCH) and Erdheim-Chester disease (ECD) with BRAFV600E mutation were released in the form of mini oral presentation at European Society for Medical Oncology Asia (ESMO Asia) Congress 2023. HLX208-LCH/ECD201 was led by Professor Jian Li from Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College and the results were initially presented at the 2023 ASCO Annual Meeting.

ECD and LCH are currently regarded as myeloid neoplasias with inflammatory properties, affecting patients’ quality of life significantly. The National Health Commission (NHC) has placed them on the "First National List of Rare Diseases"[1]. According to the 2019 edition of the Clinical Practice Guidelines for Rare Diseases issued by the National Health Commission of China [2], LCH and ECD are driven by constitutive activation of the MAPK/ERK signalling pathway with more than 50% incidence of BRAFV600E mutation. HLX208 is a potential “best-in-class” BRAF inhibitor introduced from NeuPharma with a proprietary novel chemical structure that differs 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. In April 2023, the Center for Drug Evaluation (CDE) of China National Medical Products Administration (NMPA) has granted a Breakthrough Therapy Designation (BTD) to HLX208 for the treatment of adult LCH and ECD with BRAFV600E mutation.

Its updated data released at 2023 ESMO Asia are as follows:


HLX208, a novel BRAF V600E inhibitor, in adult patients with Langerhans cell histiocytosis and/or Erdheim-Chester disease harbouring BRAF V600E mutation

Study design

In this single-arm, open-label, multicentre phase 2 study, patients with histologically confirmed Langerhans cell histiocytosis (LCH) and/or Erdheim-Chester disease (ECD) were enrolled and given orally HLX208 at 450 mg twice a day in 28-day cycles. The primary endpoint was ORR assessed by an independent radiological review committee (IRRC) per PET Response Criteria in Solid Tumors (PERCIST 1.0). Secondary endpoints included safety, other efficacy measures, and pharmacokinetics of HLX208.


As of 14 July 2023, 30 patients were enrolled. Median age was 38.5 years; 13 (43.3%) patients were male. 19 (63.3%) patients were diagnosed with LCH, 10 (33.3%) with ECD, and 1 (3.3%) had combined LCH and ECD. 8 (26.7%) patients had single system multifocal disease, while 22 (73.3%) had multisystem disease. Median follow-up duration was 10.7 months. Among the 20 efficacy evaluable patients, unconfirmed ORR was 95.0% (95% CI 75.1–99.9%) as assessed by IRRC per PERCIST 1.0. Detailed results of tumour responses are shown in Table 1. Of the 30 patients who received HLX208, 5 (16.7%) patients reported grade 3–4 treatment-related AEs, most commonly alanine aminotransferase increased (6.7%) and aspartate aminotransferase increased (6.7%). No treatment-emergent AEs leading to death occurred.


HLX208 showed promising efficacy in adult patients with LCH and/or ECD harbouring BRAFV600E mutation, with a manageable safety profile.


[1] 国家卫生健康委员会《关于公布第一批罕见病目录的通知》(国卫医发〔2018〕10号)

[2] 国家卫生健康委办公厅《罕见病诊疗指南(2019年版)》(国卫办医函〔2019〕198号)