Abstract 329MO
Background
Langerhans cell histiocytosis (LCH) and Erdheim-Chester disease (ECD) are rare histiocytic disorders with frequent BRAF V600E mutations. HLX208 is a novel BRAFV600E 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
IRRC-assessed (n=20) | Investigator-assessed (n=20) | |
Objective response rate, % (95% CI) | 95.0 (75.1–99.9) | 100 (83.2–100.0) |
Disease control rate, % (95% CI) | 100 (83.2–100.0) | 100 (83.2–100.0) |
Complete metabolic response, n (%) | 5 (25.0) | 8 (40.0) |
Partial metabolic response, n (%) | 14 (70.0) | 12 (60.0) |
Stable metabolic response, n (%) | 1 (5.0) | 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.
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