KEY TAKEAWAYS
- The phase 2 trial aimed to evaluate HLX208 in BRAF V600E+ LCH/ECD adults.
- The primary endpoint was to evaluate HLX208’s ORR. The secondary endpoint was to assess the Safety and PK profile.
- HLX208 demonstrated efficacy and safety in BRAF V600E+ LCH/ECD.
At the 2023 ASCO Annual Meeting, Xin-xin Cao and her associated researchers disclosed the findings from the phase 2 trial of HLX208, a novel BRAF V600E inhibitor, demonstrating impressive anti-tumor effectiveness in preclinical investigations for patients (pts) with Langerhans cell histiocytosis (LCH) and/or Erdheim-Chester disease (ECD) carrying the BRAF V600E mutation.
The interventional study, a single-arm, open-label study conducted across multiple centers, included pts diagnosed with histologically confirmed LCH and/or ECD. Patients received an oral administration of HLX208 at a dosage of 450 mg twice daily in 28-day cycles. The primary endpoint was the objective response rate (ORR), evaluated by an independent radiological review committee(IRRC) using the PET Response Criteria in Solid Tumors (PERCIST 1.0). Secondary endpoints included safety assessments, additional measures of efficacy, and the pharmacokinetics (PK) of HLX208.
About 30 pts were enrolled with a median age of 38.5 years, with 13 (43.3%) being male. Out of the cohort, 19 (63.3%) were diagnosed with LCH, 10 (33.3%) with ECD, and 1 (3.3%) had a combination of LCH and ECD. Among the pts, 8 (26.7%) had single system multifocal disease, while 22 (73.3%) had multisystem disease. The median follow-up duration was 10.7 months.
For the 20 pts evaluated for efficacy, the unconfirmed ORR was 95.0% (95% CI 75.1–99.9%), as assessed by the IRRC per PET Response Criteria in Solid Tumors (PERCIST 1.0).
Among the 30 pts who received HLX208, 5 (16.7%) reported grade 3–4 treatment-related adverse events (TRAEs), with the most common being increased alanine aminotransferase (6.7%) and increased aspartate aminotransferase (6.7%). No treatment-emergent AEs leading to death were observed.
The result demonstrated that HLX208 exhibited encouraging effectiveness in adult pts diagnosed with LCH and/or ECD carrying the BRAF V600E mutation. These findings suggested a potential positive outcome for using HLX208 in this specific patient population, with implications for both efficacy and safety in treating diseases associated with the BRAF V600E mutation. This study is sponsored by Shanghai Henlius Biotech.
Source: https://cslide.ctimeetingtech.com/asia2023/attendee/confcal/show/session/46
Clinical Trial: https://clinicaltrials.gov/study/NCT05092815
Cao, X.X., Wu, Y., Liu, P., et al. “329MO – HLX208, a novel BRAF V600E inhibitor, in adult patients with Langerhans cell histiocytosis and/or Erdheim-Chester disease harbouring BRAF V600E mutation” resent at ESMO ASIA. (Abstract-329 MO).
