Trial Title:
A Confirmatory Clinical Study in NSCLC Patients With MET Exon 14 Mutation (KUNPENG-2)
NCT ID:
NCT05989542
Condition:
Non-small Cell Lung Cancer
Conditions: Official terms:
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Study type:
Interventional
Study phase:
Phase 3
Overall status:
Active, not recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
PLB1001
Description:
200mg BID Oral
Arm group label:
PLB1001
Summary:
The goal of this clinical trial is to test if PLB1001 works well and safely in Non-small
cell lung cancer patients with MET exon 14 mutation. The main questions it aims to answer
are:
- If it is works well in Non-small cell lung cancer patients with MET exon 14 mutation
- If it is safety and tolerant in Non-small cell lung cancer patients with MET exon 14
mutation
Participants will
1. be given PLB1001 200mg BID,oral.
2. be received hematology and urine and ECG examinations every 14 days (First 3 months)
or every 28 days (After 3 months)
3. be received Image examination every 8 weeks(First year) or every 12 weeks(After one
year)
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. voluntarily sign a written informed consent to participate in the study and be
willing and able to comply with study-related visits and procedures;
2. Male or female aged 18 years and above;
3. patients with histologically or cytologically confirmed locally advanced or
metastatic non-small cell lung cancer (including sarcomatoid carcinoma of the lung,
according to the AJCC 8th edition of lung cancer staging, Stage IIIB - Stage IV)
(non-site pathology reports are acceptable);
4. NGS testing of tumor tissue or blood samples by a CLIA- or CAP-accredited laboratory
or a sponsor-designated central laboratory with confirmation of the presence of a
MET exon 14 mutation. and patients are required to provide sufficient tumor tissue
(archived or fresh samples) and blood samples for retrospective testing and analysis
by the central laboratory (see Laboratory Manual) to support the development of
concomitant diagnostic reagents required for the marketing of Vebreltinib. Note:
Patients who have received prior systemic antitumor therapy are preferred to have
tumor tissue obtained after disease progression on the most recent antitumor therapy
for biomarker testing;
5. Tissue sample testing confirms EGFR wild-type, ALK rearrangement negative, ROS1
rearrangement negative, and KRAS mutation negative;
6. at least one measurable lesion (per RECIST 1.1 criteria). For a lesion that has
received prior radiotherapy, it may be counted as a target lesion only if definitive
disease progression has occurred since radiotherapy;
7. an ECOG performance status score of 0-1;
8. expected survival ≥ 3 months;
9. Laboratory tests that meet the following requirements:
- Aspartate aminotransferase (AST): ≤ 3 x ULN (no liver metastases)
- Alanine aminotransferase (ALT): ≤3 × ULN (no liver metastases)
- Total bilirubin (TBIL): ≤1.5 × ULN (no liver metastases)
- AST: ≤5.0 × ULN (with liver metastases)
- ALT: ≤5.0 × ULN (with liver metastasis)
- Total bilirubin: ≤3.0 × ULN (with liver metastases)
- Platelet count: ≥75 × 10⁹/L (without blood transfusion or mono-collected
platelet transfusion or growth factor use within 10 days prior to the start of
treatment)
- Absolute neutrophil count: ≥ 1.5 × 10⁹/L (in the absence of growth factors
within 10 days prior to the start of treatment)
- Hemoglobin > 90 g/L (in the absence of blood transfusion or use of growth
factors within 10 days prior to the start of treatment)
- Coagulation index: INR≤2.0
- Serum creatinine: ≤1.5 × ULN
- Creatinine clearance (Ccr) >50 mL/min, with Ccr using the Cockcroft-Gault
formula: (140 - age[yr]) × body weight (kg) × 1.23 × (0.85, if female)/serum
creatinine (μmol/L)
- Urea/urea nitrogen: ≤1.5 × ULN
- Asymptomatic serum amylase ≤ grade 2 (NCI-CTCAE 5.0). For patients with Grade 2
serum amylase abnormalities prior to first dose, it is important to confirm
that there are no signs and/or symptoms suggestive of pancreatitis or
pancreatic injury (e.g., elevated P-amylase, abnormal pancreatic imaging
results, etc.)
- Serum lipase ≤ 1.5 × ULN;
10. the investigator is judged to be compliant and able to complete scheduled visits,
treatments and laboratory tests according to the protocol;
11. men and women of childbearing potential must agree to use effective contraception
from the time of signing the informed consent until 3 months after the last dose of
study drug. Women of childbearing potential must have a negative serum pregnancy
test within 7 days prior to the first dose of study drug.
Exclusion Criteria:
1. unwilling to provide tumor tissue or blood samples for molecular testing;
2. previous treatment with MET inhibitors or HGF-targeted therapy;
3. have symptomatic and neurologically unstable central nervous system (CNS) metastases
or CNS disease that requires increased steroid doses for control; NOTE: Patients
with CNS metastases whose symptoms have been controlled may be enrolled in this
trial. Patients with symptomatic or unstable CNS metastases must have completed
radiotherapy, or at least 2 weeks after surgical treatment of CNS tumor metastases,
prior to study entry. Patients must have stable neurologic function with no new
neurologic deficits identified on clinical examination and no new problems
identified on CNS imaging. If the patient requires steroids for the treatment of CNS
metastases, they must have been stabilized on a therapeutic dose of steroids for at
least 2 weeks prior to signing the informed consent form;
4. patients with clinically poorly controlled pleural, abdominal or pericardial
effusions who, in the judgment of the investigator, are not suitable for enrollment;
5. unstable or uncontrolled disease or conditions related to or affecting cardiac
function (e.g., unstable angina pectoris, congestive heart failure [NYHA > Class
II], unstably controlled hypertension [defined as diastolic blood pressure > 100
mmHg and/or systolic blood pressure > 160 mmHg regardless of antihypertensive
medications. initiation of antihypertensive medications or adjustment of
antihypertensive medications prior to Screening is permitted]);
6. a coagulation disorder or bleeding tendency, including an arterial or venous
thromboembolic event (including myocardial infarction, cerebrovascular accident or
transient ischemic attack, pulmonary artery embolism, deep vein thrombosis, or any
other history of severe thromboembolism) within 6 months prior to the administration
of the first study medication, any life-threatening bleeding event (including the
need for transfusional therapy, surgical or topical therapy, and ongoing drug
therapy) that Tendency to bleed in the judgment of the investigator;
7. a mean corrected QT interval (QTcF) of >470 ms on three electrocardiograms during
the screening period, calculated according to the Fridericia formula (see Appendix 5
for details), at rest; the presence of risk factors leading to prolongation of the
QTc interval such as chronic hypokalemia not corrected by supplemental therapy,
congenital or familial long QT interval syndrome, family history of the presence of
a first-degree relative with an unexplained sudden death under 40 years of age, or
combined Sudden unexplained death, or combination of any medications known to
prolong the QT interval and cause tip-twist ventricular tachycardia.
8. any significant rhythm abnormality such as complete left bundle branch block, second
or third degree heart block, medically uncontrolled ventricular arrhythmias,
supraventricular, nodal arrhythmias, and medically uncontrolled other cardiac
arrhythmias;
9. active gastrointestinal disorders (e.g., ulcerative lesions, uncontrollable nausea,
vomiting, diarrhea, and malabsorption syndromes) or other conditions (e.g.,
inability to swallow the test medication, or prior major gastrointestinal surgery)
that significantly interfere with absorption, distribution, metabolism, or excretion
of the oral study drug;
10. the presence of an active infection, including but not limited to: 1) Hepatitis B
(Hepatitis B Surface Antigen [HBsAg] positive and Hepatitis B Virus [HBV] DNA ≥ 500
IU/ml), Hepatitis C (positive for both anti-Hepatitis C Virus [HCV] antibodies and
HCV-RNA) or Human Immunodeficiency Virus (HIV) (HIV antibody positive) infections,
and syphilis positive infections; 2) Active tuberculosis; 3) Active infection (e.g.,
pneumonia) requiring systemic anti-infective therapy within 2 weeks prior to first
study drug administration;
11. known history of hypersensitivity to the active or inactive excipients of
Vebreltinib, hypersensitivity to drugs with a chemical structure similar to that of
Vebreltinib.
12. patients being treated with warfarin or any other coumarin derivative anticoagulant,
with the exception of low-dose warfarin (< 2 mg) for the prevention of central
catheter-related thrombosis;
13. presence of prior antineoplastic therapy toxicity not recovered to ≤ Grade 1
(NCI-CTCAE 5.0) or baseline, except for alopecia, skin hyperpigmentation, and Grade
2 peripheral neurotoxicity
14. any comorbid medical condition that may increase the risk of toxicity;
15. antineoplastic and investigational drug therapy within 2 weeks or ≤ 5 drug
half-lives (whichever is longer, up to a maximum of 4 weeks) prior to initiation of
the first dose of Vebreltinib. If the prior therapy was a monoclonal antibody, the
therapy must be discontinued at least 2 weeks prior to the first dose of
Vebreltinib. If the prior therapy was an oral targeted drug, the therapy must be
discontinued at least 5 drug half-lives (up to 4 weeks) prior to the first dose of
Vebreltinib. If prior therapy was an herbal antineoplastic therapy, it must be
discontinued at least 1 week prior to the first dose of Vebreltinib;
16. chest radiotherapy to the lung field ≤ 4 weeks prior to initiating treatment with
Vebreltinib or if the patient has not recovered to ≤ Grade 1 from
radiotherapy-related toxicity. For all other sites (including radiotherapy to the
thoracic spine or ribs), radiotherapy ≤ 2 weeks prior to initiation of Vebreltinib
therapy or the patient has not recovered from radiotherapy-related toxicity.
Palliative radiotherapy to bone metastatic lesions for pain relief does not require
a washout period;
17. major surgery (e.g., intrathoracic, intra-abdominal, or intra-pelvic) within 4 weeks
prior to initiation of treatment with Vebreltinib, brain metastasectomy may be
relaxed to within 2 weeks or if the patient has not recovered from the side effects
of these surgeries or is significantly traumatized, or if the patient is expected to
have a significant surgical need during the study period. Thoracoscopic biopsy
procedures and mediastinoscopy are not considered major surgery and patients may be
enrolled ≥1 week after the procedure;
18. another malignancy diagnosed within the last 3 years in addition to NSCLC and/or
requiring treatment. Completely resected basal cell and squamous skin cancers, and
completely resected carcinoma in situ of any type are excluded;
19. patients are treated with CYP3A4 potent inducer and/or potent inhibitor medications
that cannot be discontinued for at least 1 week prior to initiation of treatment
with Vebreltinib and for the duration of the study;
20. is pregnant or is breastfeeding
21. is currently participating in another interventional clinical trial or has received
an investigational drug within 2 weeks prior to the first dose of the test drug
22. other circumstances that, in the opinion of the investigator, make participation in
the study inappropriate, such as the presence of evidence of severe or uncontrolled
systemic disease, including, but not limited to, active primary immunodeficiency
disease, allogeneic organ transplantation, that make the patient unsuitable for
participation in this trial or that would impede adherence to the study protocol.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Guangdong Provincial People's Hospital
Address:
City:
Guangzhou
Zip:
510080
Country:
China
Start date:
June 29, 2023
Completion date:
September 30, 2027
Lead sponsor:
Agency:
Beijing Pearl Biotechnology Limited Liability Company
Agency class:
Industry
Source:
Beijing Pearl Biotechnology Limited Liability Company
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05989542
