The Efficacy of HLX208 (BRAF V600E Inhibitor) With Cetuximab for Metastatic Colorectal Cancer (mCRC) With BRAF V600E Mutation After First-line Treatment

Study Overview
=================
Brief Summary
-----------------
An open, multicenter phase II clinical study to evaluate safety and efficacy of HLX208 (BRAF V600E inhibitor) combined with cetuximab for metastatic colorectal cancer (mCRC) with BRAF V600E Mutation after first-line treatment

Official Title
-----------------
An Open, Multicenter Phase II Clinical Study to Evaluate Safety and Efficacy of HLX208 (BRAF V600E Inhibitor) Combined With Cetuximab in Patients With Metastatic Colorectal Cancer (mCRC)

Conditions
-----------------
CRC

Intervention / Treatment
-----------------
* Drug: HLX208
* Drug: Cetuximab Injection [Erbitux]


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age>=18Y Good Organ Function Expected survival time ≥ 3 months Metastatic/recurrent advanced BRAF+ mCRC that have been diagnosed histologically and have failed first line treatment ECOG score 0-1; Exclusion Criteria: arm 1 ： Previous treatment with BRAF inhibitors or MEK inhibitors Symptomatic brain or meningeal metastases (unless the patient has been on > treatment for 3 months, has no evidence of progress on imaging within 4 weeks prior to initial administration, and tumor-related clinical symptoms are stable). Active clinical severe infection; A history of other malignancies within two years, except for cured carcinoma in situ of the cervix or basal cell carcinoma of the skin.

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
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Never use other BRAF inhibitor therapy<br>Never use other BRAF inhibitor therapy | Drug: HLX208<br>* HLX208 450mg bid po OR 600mg bid po OR 900mg bid po<br>* Other names: BRAF V600E inhibitor;Drug: Cetuximab Injection [Erbitux]<br>* Cetuximab 500 mg/m2 IV Q2W<br>|
| Experimental: PD after other BRAF inhibitor therapy N=5 40<br>PD after other BRAF inhibitor therapy | Drug: HLX208<br>* HLX208 450mg bid po OR 600mg bid po OR 900mg bid po<br>* Other names: BRAF V600E inhibitor;Drug: Cetuximab Injection [Erbitux]<br>* Cetuximab 500 mg/m2 IV Q2W<br>|
| Experimental: SD but intolerant after other BRAF inhibitor therapy<br>SD but intolerant after other BRAF inhibitor therapy | Drug: HLX208<br>* HLX208 450mg bid po OR 600mg bid po OR 900mg bid po<br>* Other names: BRAF V600E inhibitor;Drug: Cetuximab Injection [Erbitux]<br>* Cetuximab 500 mg/m2 IV Q2W<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ORR | Objective response rate(assessed by independent radiological review committee (IRRC) based on the RECIST Version 1.1) | up to 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PFS | Progression-free survival (PFS) (assessed by IRRC and the investigator as per RECIST v1.1 ) | from the first dose until firstly confirmed and recorded disease progression or death (whichever occurs earlier),assessed up to 2 years] | 
| OS | Overall survival | from the date of first dose until the date of death from any cause，assessed up to 2 years |