329MO - HLX208, a novel BRAF V600E inhibitor, in adult patients with Langerhans cell histiocytosis and/or Erdheim-Chester disease harbouring BRAF V600E mutation

Background

Langerhans cell histiocytosis (LCH) and Erdheim-Chester disease (ECD) are rare histiocytic disorders with frequent BRAF ^V600E mutations. HLX208 is a novel BRAF^V600E inhibitor, exhibiting excellent antitumour efficacy in preclinical studies. At 2023 ASCO Annual Meeting, we presented results from the phase 2 study of HLX208 in adult patients with LCH and/or ECD harbouring BRAF ^V600E mutation. Here we report updated results after another 5.9 months of follow-up.

Methods

In this single-arm, open-label, multicentre phase 2 study, patients with histologically confirmed LCH and/or 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.

Results

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 the table. 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. Table: 329MO

Response (unconfirmed) per PERCIST 1.0

Conclusions

HLX208 showed promising efficacy in adult patients with LCH and/or ECD harbouring BRAF ^V600E mutation, with a manageable safety profile.

Clinical trial identification

NCT05092815 (released on 26 October 2021).

Editorial acknowledgement

Editorial assistance was provided by Shiqi Zhong, Zhi Hao Kwok, and Chen Hu of Shanghai Henlius Biotech, Inc.

Legal entity responsible for the study

Shanghai Henlius Biotech, Inc.

Funding

Shanghai Henlius Biotech, Inc.

Disclosure

C. Hu, X. Hou, Q. Wang, J. Zhu: Financial Interests, Personal, Full or part-time Employment: Shanghai Henlius Biotech, Inc. All other authors have declared no conflicts of interest.