Non-small-cell Lung Cancer
Conditions
Keywords
BRAF V600E mutation, NSCLC
Brief summary
This is a single-arm, open, multicenter phase II clinical study to evaluate the efficacy and safety of HL-085 capsules combined with Vemurafenib in the treatment of BRAF V600E mutated patients with unresectable locally advanced or metastatic NSCLC. Meanwhile, to explore the relationship between pop-PK characteristics, efficacy and safety in the treatment of HL-085 combined with Vemurafenib
Detailed description
This study was intended to be divided into two study cocohorts. Cohort one was BRAF V600E mutated NSCLC patients who had not received systemic treatment (first-line). Cohort 2 included patients with BRAF V600E mutated NSCLC who had received systemic therapy (second-line and above); There were 30 patients in cohort 1 and 39 in cohort 2, a total of 69 evaluable cases. A sample size of 73 patients with advanced NSCLC with BRAF V600E mutation (32 /41, respectively) was calculated at a 5% shedding rate. All patients in the first/second line and above were eligible for inclusion. The treatment regimen was HL-085 9mg BID+ Vemurafenib 720mg BID oral administration for 21 days per cycle. The primary efficacy endpoint in this study was the ORR assessed by the Independent Review Committee (IRC) according to the RECIST 1.1 Efficacy Evaluation Criteria for solid tumors. Subjects were evaluated for tumor imaging every 6 weeks (±7 days), and for complete response (CR) or partial response (PR) at the first imaging assessment, reconfirmation was performed at ≥4 weeks. Safety will be assessed by vital signs, physical examination, ECOG score, clinical laboratory tests (blood routine, blood biochemistry, coagulation function, urine routine, myocardial enzymes), 12-lead electrocardiogram (ECG), echocardiogram (ECHO) examination, and incidence and severity of AE.
Interventions
DRUGHL-085+Vemurafenib
The treatment regimen was HL-085 9mg BID+ Vemurafenib 720mg BID oral administration for 21 days per cycle. The primary efficacy endpoint in this study was the ORR assessed by the Independent Review Committee (IRC) according to the RECIST 1.1
Sponsors
Shanghai Kechow Pharma, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Inclusion Criteria: 1. Male or female aged 18-75 (inclusive) at the time of signing the informed consent; 2. Patients with locally advanced or metastatic stage IIIb, IIIc, or IV NSCLC (according to the AJCC Eighth Edition TNM staging system for lung cancer) who are confirmed by histopathology/cytology and cannot be resected by surgery can be included in the group without or after systemic treatment; 3. At baseline, genetic testing reports of BRAF V600E mutation can be provided; 4. The time interval between the end of the last anti-tumor therapy and the first administration of the study drug meets the following requirements: ≥4 weeks for cytotoxic drugs and cellular immunotherapy; PD-1/PD-L1/CTLA-4≥6 weeks; Small-molecule targeted drugs ≥2 weeks or 5 half-lives of drugs (whichever is longer); Mitomycin/nitrosourea ≥6 weeks; End time of radiotherapy ≥4 weeks (palliative local radiotherapy for pain relief ≥2 weeks), radiotherapy related adverse reactions recovered; 5. ECOG PS score 0-1; 6. Expected survival \> 3 months; 7. At least one measurable lesion in line with the RECIST v1.1 definition at baseline (if the lesion at the site of previous radiotherapy is selected as the target lesion, this lesion has obvious evidence of progression); 8. The level of organ function and related laboratory indicators must meet the following requirements: * Neutrophil count absolute value (ANC) ≥ 1.5×109/L; Platelet count ≥ 100×109/L; Hemoglobin ≥ 90g/L; * Blood biochemistry: serum total bilirubin ≤1.5 times the upper limit of normal value (ULN); For Gilbert syndrome patients, TBIL≤3×ULN; AST/ALT≤3 ULN (Allow AST/ALT≤5 ULN when liver metastasis occurs); Serum creatinine ≤1.5 ULN; Albumin ≥30 g/L; * Coagulation: prothrombin time (PT) ≤ 1.5x ULN or activated partial thrombin time (APTT) ≤ 1.5x ULN; * Creatine phosphokinase (CPK) and (hypersensitive) troponin (cTnI/T) are within normal ranges; 9. The serum pregnancy test results of fertile women must be negative within 7 days prior to the first dosing, and female subjects are willing to use adequate contraception during the trial and for at least 6 months after the last dosing of the study drug. Male subjects must consent to use contraception (non-drug or tool contraception) for at least 6 months from the start of the study until the final dose; 10. The subjects voluntarily participated in the study and signed the informed consent. The subjects had good compliance and could cooperate with the follow-up.
Exclusion criteria
*
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| ORR | through study completion, an average of 1 year | Defined as the proportion of subjects with an optimal response of CR or PR over the course of the study from enrollment to disease progression (PD), dominated by IRC assessment. CR and PR must be reassessed for confirmation ≥4 weeks after first meeting mitigation criteria; |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| DOR | through study completion, an average of 1 year | Defined as the time from the first CR or PR evaluation of tumor efficacy to the first occurrence of PD or death from any cause (whichever occurs first) |
Contacts
Primary ContactZhimei Zhu, Master
Backup ContactYuankai Shi, phD
Outcome results
None listed