HLX208 (BRAF V600E Inhibitor) in Combination With Trametinib in Patients With Advanced Solid Tumors

Study Overview
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Brief Summary
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A phase I clinical trial evaluating the safety, tolerability, pharmacokinetics, and initial efficacy of HLX208 (BRAF V600E inhibitor) in combination with trametinib in patients with advanced solid tumors

Official Title
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A Phase I Clinical Trial Evaluating the Safety, Tolerability, Pharmacokinetics, and Initial Efficacy of HLX208 (BRAF V600E Inhibitor) in Combination With Trametinib in Patients With Advanced Solid Tumors

Conditions
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Solid Tumor

Intervention / Treatment
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* Drug: HLX 208


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18Y≤Age≤75Y Good Organ Function Expected survival time ≥ 3 months Metastatic/recurrent advanced BRAF+ solid tumors that have been diagnosed histologically and have failed standard treatment Previous failure to standard treatment, intolerance to standard treatment, absence of standard treatment, or insuitability for standard treatment at this stage. ECOG score 0-1; Expected survival time of more than 3 months; Exclusion Criteria: Previous treatment with BRAF inhibitors or MEK inhibitors Symptomatic brain or meningeal metastases (unless the patient has been on > treatment for 6 months, has no evidence of progress on imaging within 4 weeks prior to initial administration, and tumor-related clinical symptoms are stable). Current or former patients with interstitial lung disease; 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. 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
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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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: ATC<br>HLX208 (dose of RP2D) and trametinib 2mg qd ,orally,Continuation of treatment until progression, withdrawal of informed consent, intolerant toxicity (whichever occurs first) | Drug: HLX 208<br>* take orally<br>* Other names: trametinib;|
| Experimental: Primary brain tumor<br>HLX208 (dose of RP2D) and trametinib 2mg qd ,orally,Continuation of treatment until progression, withdrawal of informed consent, intolerant toxicity (whichever occurs first) | Drug: HLX 208<br>* take orally<br>* Other names: trametinib;|
| Experimental: CRC(KRAS mutant)<br>HLX208 (dose of RP2D) and trametinib 2mg qd ,orally,Continuation of treatment until progression, withdrawal of informed consent, intolerant toxicity (whichever occurs first) | Drug: HLX 208<br>* take orally<br>* Other names: trametinib;|
| Experimental: other solid tumor<br>HLX208 (dose of RP2D) and trametinib 2mg qd ,orally,Continuation of treatment until progression, withdrawal of informed consent, intolerant toxicity (whichever occurs first) | Drug: HLX 208<br>* take orally<br>* Other names: trametinib;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| MTD | maximum tolerated dose | from first dose to the end of Cycle 1 (each cycle is 21 days) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| RP2D | Recommended dose for phase II clinical trials | from first dose to the end of Cycle 1 (each cycle is 21 days) | 
| Peak Plasma Concentration (Cmax) of HLX208 | pharmacokinetics | from first dose to the beginning of Cycle 4 (each cycle is 21 days) | 
| ORR | The number of patients with CR or PR divided by the total number of treated patients whose disease was measurable at baseline | from first dose to the last patient was followed up for 6 month | 
| Area under the plasma concentration versus time curve (AUC)of HLX208 | pharmacokinetics | from first dose to the beginning of Cycle 4 (each cycle is 21 days) |