Non-small-cell Lung CancerPhase 2NCT05900219
Efficacy and Safety of HL-085 Combined With Vemurafenib in BRAF V600E Patients With Non-small Cell Lung Cancer: a Phase II Clinical Study
A Phase 2 study testing HL-085+Vemurafenib in people with Non-small-cell Lung Cancer, run by Shanghai Kechow Pharma, Inc..
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Non-small-cell Lung Cancer
- What is being tested?
- HL-085+Vemurafenib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 75 participants
- Where
- No sites listed yet
- Study dates
- 24 Sep 2023to 24 Sep 2025
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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;
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- 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;
- 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;
- 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;
- The subjects voluntarily participated in the study and signed the informed consent. The subjects had good compliance and could cooperate with the follow-up.
Who cannot join
- 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;
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- 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;
- Patients who have previously received allogeneic bone marrow transplantation or organ transplantation;
- Previous or current retinal diseases, such as retinal venous obstruction (RVO), retinal arterial obstruction (RAO), retinal vasculitis, diabetic retinopathy, hypertensive retinopathy, retinal telangiectasis (Costs disease), retinal pigment epithelium detachment (RPED), etc.;
- Patients with past or current interstitial lung disease, including clinically significant radiation pneumonia (i.e. affecting activities of daily living or requiring intervention);
- Past or current neuromuscular diseases associated with elevated CPK (e.g., inflammatory myopathy, muscular dystrophy, amyotrophic lateral sclerosis, spinal muscular atrophy, rhabdomyolysis syndrome);
- Bleeding symptoms ≥ Grade 3 as defined in NCI CTCAE v5.0 occurred within 4 weeks prior to initial administration;
- Subjects with impaired heart function or clinically significant cardiovascular and cerebrovascular diseases, including any of the following:
- Acute myocardial infarction, unstable angina, or acute cerebral infarction
- Stent implantation during coronary angioplasty or within 6 months prior to initial administration
- Clinically significant unstable arrhythmias (atrial fibrillation, etc.)
- Congestive heart failure of grade II or higher as defined by New York Heart Society (NYHA) standards; Note: Subjects with grade 1 abnormal heart valve morphology recorded by ECHO (≥ Grade 2) were admitted, but subjects with moderate valve thickening were excluded;
- QT interval (QTcF) ≥ 480 msec corrected using the Fridericia formula;
- Left ventricular ejection fraction (LVEF) < 55%;
- Implantable defibrillators;
- Refractory hypertension (at least 3 consecutive months of use of at least 3 antihypertensive drugs, still unable to control blood pressure within the normal range);
- Inability to swallow capsules or refractory nausea and vomiting, malabsorption, extracorporeal bile shunt, or any significant small intestine resection that might prevent full absorption of the study drug; Chronic atrophic gastritis and gastroduodenal ulcer with bleeding risk;
- Human immunodeficiency virus (HIV) antibody positive, syphilis antibody (Anti-TP) positive, hepatitis C virus (HCV) antibody positive and HCV-RNA positive, hepatitis B virus surface antigen (HBsAg) positive and HBV-DNA positive (HBsAg positive requires further HBV DNA testing, HBV DNA≥200 IU/ml, or ≥103 copy number /ml);
- Strong inducers that affect cytochrome P450 (CYP) isoenzymes (CYP2C9, CYP3A4) that are prohibited by protocol, strong inhibitors or drugs with a narrow therapeutic window through CYP1A2 metabolism should continue to be used within 7 days prior to initial administration or during the study period;
- There was > grade 1 unmitigated toxicity associated with prior antitumor therapy prior to initial administration. Alopecia, skin pigmentation, grade 2 neurotoxicity due to prior platinum therapy, asymptomatic hypothyroidism due to immune checkpoint inhibitors requiring hormone replacement therapy, and medicated hyperglycemia were excluded;
- The presence of any serious and/or unstable pre-existing condition, mental illness, or other condition that may interfere with the subject's safety, obtaining informed consent, or complying with study procedures. Including, but not limited to, severe diabetes (fasting blood glucose ≥13.9mmol/L), active infections (such as active tuberculosis), active bleeding, or other serious diseases requiring systematic treatment;
- lactating women;
- The investigator determined that the subjects had a serious or uncontrolled systemic disease that would make them unfit to participate in the study or would affect protocol compliance or significantly interfere with the correct assessment of the safety, toxicity, or efficacy of the study drug.
Trial locations and contacts
No sites are listed yet.
About this study
Official title: 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)
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
Read the 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.
- Conditions
- Non-small-cell Lung Cancer
- Being tested
- HL-085+Vemurafenib
- Keywords
- BRAF V600E mutation, NSCLC
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
HL-085+VemurafenibDrug
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
| Study group | Role | What they receive |
|---|---|---|
| Assigned Interventions | Experimental | The treatment regimen was HL-085 9mg BID+ Vemurafenib 720mg BID oral administration Receives: Drug: HL-085+Vemurafenib |
What is being measured
The primary outcome is the main question the study is designed to answer.
ORR
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;
Measured: through study completion, an average of 1 year
Secondary outcomes (1)
DOR
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)
Measured: through study completion, an average of 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jun 2023
- Study start24 Sep 2023 (estimated)
- Primary completion24 Sep 2025 (estimated)
- Study completion24 Sep 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Non-small-cell Lung CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 75 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Shanghai Kechow Pharma, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Yuankai Shi, phD, Principal investigator, Cancer Hospital Chinese Academy of Medical Science
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05900219
- Sponsor's protocol ID
- HL-085-203
- Status last verified
- Jun 2023
- First submitted
- 29 May 2023
- Last updated
- 12 Jun 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 Jun 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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)
- ClinicalTrials.gov ID
- NCT05900219
- Acronym / sponsor ID
- HL-085-203
- Conditions
- Non-small-cell Lung Cancer
- Keywords
- BRAF V600E mutation, NSCLC
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 75 participants (estimated)
- Lead sponsor
- Shanghai Kechow Pharma, Inc.Industry (pharma, biotech, devices)
- Study start
- 24 Sep 2023 (estimated)
- Primary completion
- 24 Sep 2025 (estimated)
- Study completion
- 24 Sep 2025 (estimated)
- First posted
- 12 Jun 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Assigned Interventions | Experimental | Drug: HL-085+VemurafenibThe treatment regimen was HL-085 9mg BID+ Vemurafenib 720mg BID oral administration |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
Key exclusion criteria (30 listed)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| HL-085+VemurafenibThe 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 | Drug | Assigned Interventions |
Primary outcome
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;
1 secondary outcome
DOR
Time frame: through study completion, an average of 1 year
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Jun 2023.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Yuankai Shi, phD principal investigator
Cancer Hospital Chinese Academy of Medical Science
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing HL-085+Vemurafenib in people with Non-small-cell Lung Cancer, run by Shanghai Kechow Pharma, Inc..
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 30 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 12 Jun 2023. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Zhimei Zhu, Master (15201345822, zhuzm@kechowpharma.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
ORR (time frame: through study completion, an average of 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Jun 2023.