The Efficacy and Safety of HLX208 in Adult Langerhans Cell Histiocytosis (LCH) and Erdheim-Chester Disease (ECD) With BRAF V600E Mutation

Study Overview
=================
Brief Summary
-----------------
The purpose of this study was to assess safety, efficacy and PK in adult Langerhans Cell Histiocytosis (LCH) and Erdheim-Chester Disease (ECD) given HLX208 (BRAF V600E inhibitor).

Official Title
-----------------
A Single-arm, Open Label, Multicenter Phase II Clinical Study in Rare Diseases to Evaluate Safety, Efficacy and PK of HLX208 for Adult Langerhans Cell Histiocytosis (LCH) and Erdheim-Chester Disease (ECD) With BRAF V600E Mutation

Conditions
-----------------
Langerhans Cell Histiocytosis, Erdheim-Chester Disease, LCH, ECD

Intervention / Treatment
-----------------
* Drug: HLX208


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Volunteer to participate in the clinical study; Aged ≥ 18 years; Confirmed adult patients with LCH and/or ECD with BRAF V600E mutation; At least one measurable lesion as per PERCIST v1.0; Expected survival time ≥ 3 months; ECOG score 0-2; Exclusion Criteria: Previous treatment with BRAF inhibitors or MEK inhibitors; A history of other malignancies within two years, except for cured cervical carcinoma in situ, basal cell carcinoma of the skin, adenocarcinoma in situ of the lung, or tumors that do not require interventional treatment after radical surgery; Severe active infections requiring systemic anti-infective therapy; Other anti-tumor treatments, such as chemotherapy, targeted therapy, or radiation therapy (except palliative radiation therapy), may be given during the study period.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HLX208<br>Participants receive HLX208 450mg bid po | Drug: HLX208<br>* HLX208 450mg bid po<br>* Other names: BRAF V600E inhibitor;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ORR | Objective response rate(assessed by independent review committee (IRC) based on the PERCIST Version 1.0) | up to 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AEs | Incidence and severity of adverse events | up to 1 year | 
| ORR | Objective response rate(assessed by the investigator based on the PERCIST v1.0) | up to 1 year | 
| ORR | Objective response rate(assessed by IRC and the investigator based on the RECIST v1.1) | up to 1 year | 
| DCR | Disease control rate (assessed by IRC and the investigator as per PERCIST v1.0 and RECIST v1.1 ) | up to 1 year | 
| TTR | Time to response(assessed by IRC and the investigator as per PERCIST v1.0 and RECIST v1.1) | up to 1 year | 
| PFS | Progression-free survival (PFS) (assessed by IRC and the investigator as per PERCIST v1.0 and RECIST v1.1 ) | from the first dose until firstly confirmed and recorded disease progression or death (whichever occurs earlier),assessed up to 1 year | 
| OS | Overall survival | from the date of first dose until the date of death from any cause，assessed up to 1 year | 
| Cmax | Maximum Plasma Concentration | from the date of first dose to 85 days | 
| Tmax | Time of Maximum Plasma Concentration | from the date of first dose to 85 days | 
| AUC | Area Under the Curve | from the date of first dose to 85 days |