A Single-arm, Open, Multicenter Phase II 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 Non-small Cell Lung Cancer (NSCLC)
Overview
- Phase
- Phase 2
- Intervention
- HL-085+Vemurafenib
- Conditions
- Non-small-cell Lung Cancer
- Sponsor
- Shanghai Kechow Pharma, Inc.
- Enrollment
- 75
- Primary Endpoint
- ORR
- Status
- Not yet recruiting
- Last Updated
- 2 years ago
Overview
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Inclusion Criteria:
- •Male or female aged 18-75 (inclusive) at the time of signing the informed consent;
- •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;
- •At baseline, genetic testing reports of BRAF V600E mutation can be provided;
- •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;
- •ECOG PS score 0-1;
- •Expected survival \> 3 months;
- •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);
- •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;
Exclusion Criteria
- •Exclusion Criteria:
- •Patients who are known to have an allergic reaction to any BRAF and/or MEK inhibitors and their excipients or have an allergic predisposition;
- •Patients with EGFR mutation, ALK fusion and other positive driver genes;
- •Previous history of antitumor and surgical treatment conforms to any of the following:
- •Being in the treatment phase of another clinical study within 4 weeks prior to initial dosing (except for patients participating in overall survival follow-up);
- •Has undergone major surgery or has not fully recovered from previous invasive procedures within 4 weeks prior to initial dosing (other than baseline tumor biopsy);
- •Previous use of MEK inhibitors, including but not limited to trametinib, smeitinib, caubitinib, pimetinib, and/or BRAF inhibitors, including but not limited to vermofinib, dalafenib, and Conefenib;
- •Symptomatic or untreated brain metastases, meninges, or spinal cord compression (imaging instability, symptomatic lesion, need for hormonal or dehydration treatment); Subjects with asymptomatic and stable brain metastases (brain lesions ≥4 weeks stable without progression) could be enrolled;
- •Pleural effusion, pericardial effusion and abdominal effusion that still cannot be controlled after clinical intervention;
- •Patients with malignancies other than the type of tumor studied within 3 years prior to initial administration, except local cancers that have been apparently cured or have been free of disease for at least 3 years, such as basal or squamous cell skin cancer, superficial bladder cancer, prostate cancer in situ, cervical cancer in situ, or ductal carcinoma in situ of the breast;
Arms & Interventions
Assigned Interventions
The treatment regimen was HL-085 9mg BID+ Vemurafenib 720mg BID oral administration
Intervention: HL-085+Vemurafenib
Outcomes
Primary Outcomes
ORR
Time Frame: 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 Outcomes
- DOR(through study completion, an average of 1 year)