Trial Title:
Study of BEBT-109 in Subjects With Non-Small Cell Lung Cancer Carrying EGFR Exon 20 Insertion Mutations
NCT ID:
NCT06514027
Condition:
Non Small Cell Lung Cancer
Conditions: Official terms:
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Carboplatin
Pemetrexed
Conditions: Keywords:
BEBT-109
EGFR exon 20 insertion mutations
Drug combination
First-line treatment
Safety
Efficacy
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Not yet recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Parallel Assignment
Intervention model description:
This study initially sets up two cohorts. In cohort 1, the treatment is BEBT-109 combined
with investigator-selected chemotherapy (injectable pemetrexed disodium combined with
carboplatin or cisplatin injection). In cohort 2, the treatment is monotherapy with
BEBT-109 (BEBT-109 capsule at a dose of 180mg, taken orally once daily). Based on
different dosing regimens of BEBT-109 capsules, cohort 1 is divided into three dose
groups: A (BEBT-109 capsule at a dose of 180mg, taken orally once daily), B (BEBT-109
capsule at a dose of 120mg, taken orally twice daily), and C (BEBT-109 capsule at a dose
of 120mg, taken orally once daily).
The decision to initiate cohort 2 will be based on the safety and efficacy results from
cohort 1.
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
BEBT-109 Capsules
Description:
BEBT-109 Capsules: Administration and Dosage: Oral administration, 120mg or 180mg;
Frequency and Duration of Administration: Once a day or twice a day,and 21 days as a
treatment cycle.
Arm group label:
BEBT-109 monotherapy
Arm group label:
Dose group A of BEBT-109 combined with investigator-selected chemotherapy
Arm group label:
Dose group B of BEBT-109 combined with investigator-selected chemotherapy
Arm group label:
Dose group C of BEBT-109 combined with investigator-selected chemotherapy
Other name:
KCBT-1083
Intervention type:
Drug
Intervention name:
Pemetrexed Disodium for Injection
Description:
Pemetrexed Disodium for Injection: Administration and Dosage: Intravenous infusion,
500mg/m^2; Frequency and Duration of Administration: On the first day of each cycle,and
21 days as a treatment cycle.
Arm group label:
Dose group A of BEBT-109 combined with investigator-selected chemotherapy
Arm group label:
Dose group B of BEBT-109 combined with investigator-selected chemotherapy
Arm group label:
Dose group C of BEBT-109 combined with investigator-selected chemotherapy
Intervention type:
Drug
Intervention name:
Carboplatin Injection
Description:
Carboplatin Injection: Administration and Dosage: Intravenous infusion, AUC=5 mg/ml.min,
with a single dose not exceeding 800 mg; Frequency and Duration of Administration: On the
first day of each cycle for the first four cycles, and 21 days as a treatment cycle,
totaling four cycles.
Arm group label:
Dose group A of BEBT-109 combined with investigator-selected chemotherapy
Arm group label:
Dose group B of BEBT-109 combined with investigator-selected chemotherapy
Arm group label:
Dose group C of BEBT-109 combined with investigator-selected chemotherapy
Intervention type:
Drug
Intervention name:
Cisplatin Injection
Description:
Cisplatin Injection: Administration and Dosage: Intravenous infusion, 75 mg/m^2;
Frequency and Duration of Administration: On the first day of each cycle for the first
four cycles, and 21 days as a treatment cycle, totaling four cycles.
Arm group label:
Dose group A of BEBT-109 combined with investigator-selected chemotherapy
Arm group label:
Dose group B of BEBT-109 combined with investigator-selected chemotherapy
Arm group label:
Dose group C of BEBT-109 combined with investigator-selected chemotherapy
Summary:
This is a multicenter, open Phase II clinical study to evaluate the efficacy, safety, and
pharmacokinetic characteristics of BEBT-109 combined with injectable pemetrexed disodium
and carboplatin or cisplatin injection as first-line treatment for locally advanced,
recurrent, or metastatic non-small cell lung cancer carrying EGFR exon 20 insertion
mutations.
Detailed description:
This study initially sets up two cohorts. In cohort 1, the treatment is BEBT-109 combined
with investigator-selected chemotherapy (injectable pemetrexed disodium combined with
carboplatin or cisplatin injection). In cohort 2, the treatment is BEBT-109 monotherapy
(BEBT-109 capsule at a dose of 180mg, taken orally once daily). Based on different dosing
regimens of BEBT-109 capsules, cohort 1 is divided into three dose groups: A (BEBT-109
capsule at a dose of 180mg, taken orally once daily), B (BEBT-109 capsule at a dose of
120mg, taken orally twice daily), and C (BEBT-109 capsule at a dose of 120mg, taken
orally once daily). Dose group A will first enroll six subjects to receive one cycle (a
treatment cycle is 21 days) of drug treatment, and the safety data of subjects in dose
group A will determine whether to adjust the dose for cohort 1 or to initiate other dose
groups. If ≤2 subjects experience dose-limiting toxicity (DLT) during the DLT observation
period, dose group A will be expanded to 20-30 subjects, and the decision to initiate
dose group B will be made jointly by the investigators and the sponsor. If more than 2
subjects experience DLT, the decision to continue the study or to initiate dose group C
will be made jointly by the investigators and the sponsor. Subjects in dose groups B and
C will also initially enroll six subjects to undergo DLT safety follow-up, and then the
decision to expand to 20-30 subjects will be made jointly by the investigators and the
sponsor.
The decision to initiate cohort 2 will be based on the safety and efficacy results from
cohort 1.
Each subject's study process includes three phases: screening, treatment, and follow-up.
During the treatment period, subjects will undergo tumor assessments every 6 weeks ± 7
days. After discontinuing treatment, subjects will enter the follow-up period, where
subjects without progressive disease (PD) will receive efficacy follow-up every 6 weeks ±
7 days (until tumor progression, death, or other antitumor treatment is initiated), and
survival follow-up every 3 months (± 2 weeks). All subjects will receive study drug
treatment until PD, death, intolerable toxicity occurs, or the subject withdraws informed
consent (whichever occurs first).
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Participants have a comprehensive understanding, voluntarily sign the Informed
Consent Form (ICF), and are capable of completing all trial procedures;
2. Age ≥18 years old, both males and females are eligible;
3. According to the 8th edition of the American Joint Committee on Cancer（AJCC）TNM
staging criteria for lung cancer: patients with histologically or cytologically
confirmed non-squamous non-small cell lung cancer (NSCLC) that is unresectable and
intolerant or refuses radical synchronous radiochemotherapy, with locally advanced
(stage IIIB or IIIC), recurrent, or metastatic (stage IV) disease;
4. No prior systemic treatment for locally advanced (stage IIIB or IIIC) or
recurrent/metastatic (stage IV) NSCLC. Note: 1) Neoadjuvant/adjuvant therapy is
allowed as long as it has been completed at least 6 months before the disease is
diagnosed as locally progressive or metastatic tumor; 2) Participants who have
failed treatment with savolitinib in the past are allowed;
5. EGFR exon 20 insertion mutations confirmed by peripheral blood or tumor tissue
testing conducted by a tertiary hospital or a qualified third-party testing agency,
and records must be provided. Patients may have only EGFR exon 20 insertion
mutations or may also have other EGFR or HER2 mutations;
6. At least one measurable lesion that meets the RECIST V1.1 criteria during the
screening period. Lesions previously treated with radiotherapy cannot be used as
target lesions unless there is clear radiological progression after radiotherapy;
7. Eastern Cooperative Oncology Group (ECOG) performance status score of 0-1, and no
decline in performance status within two weeks before the screening period, with an
expected survival time ≥12 weeks;
8. Provided that the subject has not received blood transfusion, erythropoietin,
recombinant human thrombopoietin, or colony-stimulating factor treatment within 14
days before the screening period, laboratory tests indicate that the subject has
adequate organ function, including:
- Absolute neutrophil count (ANC) ≥1.5×10^9/L; Platelet count (PLT) ≥100×10^9/L;
Hemoglobin (HGB) ≥90 g/L;
- Total serum bilirubin (TBIL) ≤1.5×upper limit of normal (ULN) (for patients
with Gilbert's syndrome, total bilirubin ≤3×ULN is allowed);
- AST and ALT ≤2.5×ULN (for those with liver metastasis, AST and ALT ≤5×ULN is
allowed);
- Creatinine clearance ≥45 ml/min (calculated according to the Cockcroft-Gault
formula), and urine protein ≤1+ or for subjects with urine protein ≥2+, the
24-hour urine protein total is ≤1 g/24 h;
- Activated partial thromboplastin time (APTT) ≤1.5×ULN, prothrombin time (PT)
≤1.5×ULN, international normalized ratio (INR) ≤1.5×ULN;
9. Participants with a history of liver cirrhosis have a Child-Pugh score of A or B ≤7
at screening;
10. The QT interval evaluated by ECG at screening is normal, defined as the corrected QT
interval (Fridericia) (QTcF) ≤450 ms (for males) or ≤470 ms (for females) (those not
meeting the standard need to be retested twice, and the average corrected value of
the three measurements is taken);
11. Male and female participants of childbearing potential must agree to use reliable
contraceptive methods (hormonal or barrier methods) during the study period and for
at least 6 months after the last administration of the drug, and must not
breastfeed, with a negative blood pregnancy test before the first administration.
Exclusion Criteria:
1. History of severe allergic diseases (such as uncontrollable asthma), severe drug
(including investigational drugs not yet marketed) allergies, or known allergies or
intolerance to any drug or drug component in this study;
2. Diagnosis of other primary malignant tumors besides NSCLC, except for the following:
non-melanoma skin cancer or cervical carcinoma in situ that has been adequately
treated and cured, non-metastatic prostate cancer, or other primary malignant tumors
that have been clearly recurrence-free for at least 3 years since the last treatment
and have a low potential risk of recurrence;
3. Major surgical procedures within 28 days before the first administration of the
study drug, planned surgery during the study period, or postoperative complications
from surgery performed within 2 months before the first administration of the study
drug (except for minor surgeries that the investigator deems do not affect
participation in the trial, such as catheter placement or minimally invasive
biopsy);
4. Presence of pleural effusion, ascites, or pericardial effusion with significant
symptoms or requiring drainage;
5. Poorly controlled diabetes mellitus. Definition: Hemoglobin A1C (HbA1c) ≥8%; or 7% ≤
Hemoglobin A1C < 8%, accompanied by clinical symptoms of diabetes, such as polyuria,
polydipsia, polyphagia, and weight loss. (Subjects who have not been adequately
treated to control blood sugar, after adjusting the drug treatment plan, with
fasting blood glucose ≤10 mmol/L, and deemed suitable to participate in this study
by the investigator, can be included);
6. Received live vaccines within 28 days before the first administration of the study
drug or plan to receive any live vaccines during the study period;
7. Subjects with a tendency to bleed or evidence of bleeding, including:
1. History of active ulcers or perforations of the stomach and duodenum within 6
months before the first dose, persistent positive fecal occult blood, history
of gastrointestinal bleeding such as ulcerative colitis;
2. History of hemoptysis (defined as blood that is bright red or 2.5 ml) within 2
weeks before the first dose, or the presence of unhealed wounds, ulcers, or
fractures;
3. Vasculitis;
4. Other conditions that may cause bleeding as determined by the investigator;
8. Presence of severe gastrointestinal functional abnormalities that may affect the
intake, transport, or absorption of the test drug (such as inability to swallow,
uncontrollable vomiting, history of extensive gastrointestinal resection, chronic
diarrhea, long-term use of proton pump inhibitors (PPIs) for gastric diseases,
Crohn's disease, ulcerative colitis, intestinal obstruction, etc.);
9. Presence of central nervous system (CNS) metastasis, except for those who are
asymptomatic, have stable disease, and do not require drug treatment within 4 weeks
before the start of the study treatment;
10. Current spinal cord compression (symptomatic or asymptomatic, and detected by
radiographic examination) or suspected meningeal disease (symptomatic or
asymptomatic);
11. Imaging (CT or MRI) shows that the tumor invades major blood vessels or is not
clearly demarcated from major blood vessels;
12. Significant clinical cardiovascular and cerebrovascular diseases within 6 months
before the first study drug administration, including but not limited to:
e. Acute myocardial infarction, unstable angina; f. New York Heart Association
(NYHA) class III or IV congestive heart failure; g. Left ventricular ejection
fraction <50% measured by echocardiography or multigated acquisition (MUGA) scan or
with severe wall motion abnormalities; h. History of clinically significant
ventricular arrhythmias (such as sustained ventricular tachycardia, ventricular
fibrillation, torsades de pointes); i. Subjects with poorly controlled hypertension,
with systolic blood pressure >160 mmHg or diastolic blood pressure >100 mmHg; j.
Arterial/venous thrombotic events, such as cerebrovascular accidents (including
transient ischemic attacks), deep vein thrombosis, and pulmonary embolism; low
molecular weight heparin treatment is allowed, and the use of nonsteroidal
anti-inflammatory drugs (NSAIDs) or antiplatelet drugs (such as aspirin (>325
mg/day), clopidogrel (>75 mg/day), dipyridamole, ticlopidine, or cilostazol, etc.)
is prohibited throughout the study period; k. Other arrhythmias deemed unsuitable
for inclusion in this study by the investigator (such as third-degree
atrioventricular block);
13. Presence of other severe or uncontrolled diseases that the investigator deems
unsuitable for participation in this clinical trial or may affect the subject's
compliance with the study protocol, including but not limited to:
1. Interstitial lung disease, radiation pneumonitis or drug-related pneumonitis
requiring steroid treatment;
2. History of uncontrolled hereditary or acquired thrombotic diseases;
3. Persistent or active infections, including but not limited to: hepatitis B
virus (meeting both hepatitis B surface antigen positive or hepatitis B e
antigen positive, and HBV-DNA greater than the upper limit of normal of the
center's laboratory), hepatitis C virus (meeting both HCV-Ab positive and
HCV-RNA positive), human immunodeficiency virus (HIV-Ab positive), syphilis
non-specific antibody positive (rapid plasma reagin [RPR] or toluidine red
unheated serum test [TRUST]) without clinical symptoms, or other active
infections that require systemic treatment within 14 days before the first
study drug administration;
4. Severe or unhealed wounds, ulcers, or fractures;
14. History of drug or alcohol abuse or mental illness;
15. Use of drugs or herbal supplements that are strong inhibitors or inducers of CYP 3A4
and CYP 2C8 within 14 days before the first administration of the study drug ;
16. Received >30Gy of non-thoracic radical radiotherapy within 28 days before the first
dose, >30Gy of thoracic radiotherapy within 24 weeks before the first dose, and
≤30Gy of palliative radiotherapy within 14 days before the first dose;
17. Participation in another clinical trial and drug administration within 4 weeks
before the first dose;
18. Other conditions deemed unsuitable for entry into this study by the investigator.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Sun Yat-sen University Cancer Center
Address:
City:
Guangzhou
Zip:
510060
Country:
China
Contact:
Last name:
Ju Yang, Master
Phone:
+86-13408523335
Email:
ju.yang@bebettermed.com
Start date:
July 2024
Completion date:
November 2027
Lead sponsor:
Agency:
BeBetter Med Inc
Agency class:
Industry
Source:
BeBetter Med Inc
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06514027
