Trial Title:
Study of BEBT-607 Tablets in The Treatment of Advanced or Metastatic Solid Tumors With KRAS G12C Mutation
NCT ID:
NCT06117371
Condition:
Advanced or Metastatic Solid Tumor
KRAS G12C Mutation
Conditions: Official terms:
Neoplasms
Conditions: Keywords:
BEBT-607
Safety
Tolerance
effectiveness
Pharmacokinetics
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Parallel Assignment
Intervention model description:
Phase Ⅰa:
Six dose levels are carried out, and the initial dose of BEBT-607 tablets is set as
100mg/ day. The climbing study is carried out by accelerated titration method combined
with "3+3" mode.
Phase Ⅰb:
According to the pharmacokinetics, safety, and preliminary efficacy results of phase Ⅰa ,
one to three cohorts with target dose or tumor species are selected for dose extension
trial, in which participants receive continuous administration of the experimental drug
BEBT-607 tablets until disease progression or toxicity became intolerable or patients
stopped or died.
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
BEBT-607Tablets
Description:
PhaseⅠa:100mg,200mg,300mg,400mg,600mg or 800mg/day,50mg,100mg,150mg,200mg,300mg or 400mg
each time, once a day in the single administration phase and twice a day in the
continuous administration phase (only once on the 28th day of the first cycle) for 28
days,28 days is as a treatment cycle.
PhaseⅠb:300mg,400mg or 600mg/day, 150mg,200mg or 300mg each time,twice a day (only once
on day 1 and day 28 of the first cycle), continuous administration for 28 days,28 days is
as a treatment cycle.
Arm group label:
Monotherapy group 1
Arm group label:
Monotherapy group 2
Arm group label:
Monotherapy group 3
Arm group label:
Monotherapy group 4
Arm group label:
Monotherapy group 5
Arm group label:
Monotherapy group 6
Arm group label:
Monotherapy group 7
Arm group label:
Monotherapy group 8
Arm group label:
Monotherapy group 9
Other name:
C200825009-FP
Summary:
This is a two-phase, multicenter, open phase I clinical study, with phase Ia as dose
escalation phase and phase Ib as dose expansion phase, to evaluate the safety
tolerability and pharmacokinetic characteristics of BEBT-607 tablets in patients with
advanced or metastatic solid tumors associated with KRAS G12C mutation. To evaluate the
efficacy of BEBT-607 tablets in the treatment of patients with advanced or metastatic
solid tumors with KRAS G12C mutation, and to determine the recommended dose (RP2D) for
Phase II clinical trials of BEBT-607 tablets in patients with advanced or metastatic
solid tumors with KRAS G12C mutation.
Detailed description:
Phase Ⅰa:
The dose escalation plan is to carry out about 6 dose levels. The initial dose of
BEBT-607 tablets is set at 100mg/ day, and the subsequent dose groups are first increased
by 100%. If a case of drug-related grade 2 non-hematological toxicity or grade 3
hematological toxicity is found and does not reach DLT, the subsequent dose groups are
increased by 50%. If one case of dose limiting toxicity(DLT) is found and does not reach
maximum tolerated dose(MTD ), the subsequent dose group is increased by 33%（Doses are
rounded to multiples of 100mg）.The single dose is 1/2 of the total daily dose, and the
single administration phase is administered once a day, and the continuous administration
phase is administered twice a day (only once on the 28th day of the first cycle).
Phase Ⅰb:
According to the pharmacokinetics, safety and preliminary efficacy results of phase Ⅰa
dose escalation phase, one to three cohorts with target dose or tumor species are
selected for dose extension trial, and a maximum of 30 subjects are enrolled in each
cohort. The subjects receive BEBT-607 tablets twice a day, orally before breakfast and
before dinner, respectively. There is a treatment cycle every 28 days (On days 1 and 28
of the first cycle, the drug is administered only once before breakfast). The study
process for each subject consisted of three phases: screening, treatment, and follow-up.
During treatment, participants are required to undergo safety checks every four weeks
from the first dose, tumor assessments every eight weeks, safety follow-up at the end of
treatment 28 days after the last dose, efficacy follow-up every eight weeks, and survival
follow-up every three months.
Participants will need to understand the requirements and risks of the trial, sign an
informed consent form, accept the dosing regimen required by the trial protocol, and
follow the investigator's guidance.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Age: ≥18 years old, gender unlimited.
2. Patients with histologically confirmed locally advanced or metastatic solid tumors
who have failed standard therapy, are intolerant to standard therapy, or have no
standard therapy.
A. For patients with Non Small Cell Lung Cancer(NSCLC), previous first-line
treatment has failed (including chemotherapy or immunotherapy or targeted therapy).
B. For patients with colorectal cancer, at least previously experienced a systemic
treatment regimen (patients with colorectal cancer and high microsatellite
instability must have received at least programmed death 1(PD-1) or programmed cell
death-Ligand 1(PD-L1) therapy if clinically applicable).
C. Patients with solid tumors other than NSCLC or colorectal cancer should have
received at least systemic therapy and treatment failure.
3. Patients with stage I b are required to have at least one measurable lesion as
defined by Response Evaluation Criteria in Solid Tumors Version 1.1(RECIST1.1).
Tumor lesions that have previously received radiotherapy or other local treatment
are considered measurable lesions only if disease progression at the treatment site
is clearly documented after completion of treatment.
4. The ECOG score is 0-1, and there is no decline in physical agility in the two weeks
before the first medication.
5. Expected survival is at least 12 weeks.
6. For patients with KRAS G12C mutation, previously confirmed genomic KRAS GI2C
mutation results in tumor tissue specimens and hematological specimens were
acceptable.
7. Good organ and bone marrow function, provided no blood transfusion has been received
within 14 days prior to the screening period, and these results should be completed
within 7 days prior to initiation of study therapy:
1. Bone marrow function should be satisfied: Absolute Neutrophil Count
(ANC)≥1.5×10^9/L; Platelet count (PLT)≥100×10^9/L: hemoglobin (Hb)≥9g/dL.
2. Renal function: serum creatinine (Cr)≤1.5 times the upper limit of normal or
creatinine clearance ≥50ml/min as calculated using the Cockcroft-Gault formula.
3. Liver function: Total bilirubin (TBIL)≤1.5×ULN(TBIL≤2.0×ULN for subjects with
documented Gilbert syndrome or TBIL≤3.0×ULN for subjects with indirect
bilirubin levels indicating the source of extrahepatic elevation); Alanine
aminotransferase (ALT) and aspartate aminotransferase (AST)≤2.5×ULN(ALT and
AST≤5×ULN if liver metastasis occurs).
4. Coagulation function: prothrombin time (PT) or partial thromboplastin time
(PTT)≤1.5× upper limit of normal (ULN), or international normalized ratio
(INR)≤1.5 or within the target range (if prophylactic anticoagulant therapy is
performed).
5. Thyroid function: Thyroid function tests are normal or abnormally asymptomatic
and do not require treatment.
8. The elution period of macromolecular drugs and intravenous chemotherapy drugs is ≥4
weeks, and the elution period of oral fluorouracil and small-molecule targeted drugs
is ≥2 weeks.
9. For fertile men and women, it is necessary to be willing to use an appropriate
contraceptive method 30 days before the first study drug administration and 6 months
after the last study drug administration.
10. Did not participate in clinical trial as a subject within 1 month before
participating in this trial.
11. Remission to baseline severity or national cancer institute common terminology
criteria for adverse events(NCI CTCAE) version 5.0≤ level 1 of all acute toxic
reactions from previous anticancer treatments or surgical procedures (except for
alopecia or other toxicities deemed by the investigator to be of no safety risk to
the patient).
12. Willing to sign informed consent after comprehensive understanding.
Exclusion Criteria:
1. Advanced patients with a short-term risk of life-threatening complications (patients
with visceral crisis).
2. Symptomatic or unstable central nervous system(CNS) metastasis, characterized by
clinically symptomatic cerebral edema, spinal cord compression, cancerous
meningitis, pia meningeal disease, and/or progressive growth. Stable is defined as:
1) seizure-free status continued for >12 weeks with or without antiepileptic drugs;
2) glucocorticoids is not required; 3) Continuously multiple consecutive imaging
examinations (scan interval of at least 8 weeks) showed a stable state.
3. Known impairment of gastrointestinal (GI) function or Gl diseases that may
significantly affect the absorption or metabolism of oral drugs.
4. Patients who had major surgery (or planned major surgery during the study period),
chemotherapy, radiation therapy, any investigational drug, or other anticancer
therapy within 4 weeks prior to study entry.
5. Known or suspected allergic symptoms to any component of BEBT-607 tablets.
6. The patient received the following treatments in the 7 days prior to study beginning
and plans to use the following drugs throughout the regimen: drugs known to be
potent inhibitors/inducers of cytochrome P450 3A4(CYP3A4), cytochrome P450
2C8(CYP2C8), and cytochrome P450 2D6(CYP2D6); Drugs known to significantly lengthen
the QT interval.
7. At rest, QT interval (QTc)>470msec(female) or >450msec(male) of Fridericia's mean
correction from 3 electrocardiogram (ECG) tests (only retest and take 3 mean
corrections if the first ECG indicates QTc>470msec(female) or >450msec(male)); A
history of long QT syndrome or a proven long QT synthesis Family history: Clinically
significant history of ventricular arrhythmias, or current use of antiarrhythmic
drugs or implantation of a defibrillation device for the treatment of ventricular
arrhythmias.
8. Uncontrolled electrolyte disturbances may affect the effect of QTc protractive drugs
(e.g., hypocalcaemia <1.0mmol/L, hypokalemia < lower limit of normal).
9. Prior combination of severe/unstable angina pectoris, persistent arrhythmia of NCI
CTCAE version 5.0≥level 2, atrial fibrillation of any level, symptomatic congestive
heart failure, cerebrovascular accident (including transient ischemic attack or
symptomatic pulmonary embolism), myocardial infarction, or coronary/peripheral
artery bypass graft within 6 months.
10. Patients with stroke or other severe cerebrovascular disease in the 12 months prior
to enrollment.
11. Uncontrolled active severe infections and clinically significant active infections
including hepatitis B (HBV), hepatitis C (HCV), known human immunodeficiency virus
(HIV) or acquired immunodeficiency syndrome (AIDS) related diseases. Active
hepatitis B is defined as positive for Hepatitis B surface antigen (HBsAg) and/or
Hepatitis Be antigen (HBeAg) with HBV-DNA≥2000IU/ml(equivalent to 10^4 copies /ml);
Active hepatitis C is defined as HCV RNA above the upper limit of detection.
12. There is a third space effusion that cannot be controlled by drainage or other
methods (such as excessive pleural fluid and ascites).
13. In the investigator's judgment, there are accompanying diseases of seriously
patient's safety endangered or patients completing the study affected (such as
uncontrolled hypertension, uncontrolled diabetes, severe autoimmune disease,
uncontrolled interstitial pneumonia, and thyroid disease).
14. Other severe acute or chronic medical or psychiatric conditions or abnormalities in
laboratory tests that may increase the risk of participation in the study or
increase the risks associated with the administration of study drugs, or interfere
with the study results, and other conditions in which the investigator considers the
patient to be unsuitable for participation in the study.
15. Pregnant or lactating women. Defined as women in a state from conception to
termination of pregnancy, identified by laboratory human chorionic gonadotropin
(hCG) test within 7 days before the start of the study.
16. Recent or active suicidal ideation or behavior.
17. For patients with other malignancies or a history of other malignancies, except for
basal cell or squamous cell carcinoma of the skin, papillary carcinoma of the
thyroid gland, carcinoma in situ of the cervix and ductal carcinoma in situ of the
breast, which has been effectively controlled in the past, is non-invasive and has
not recurred or metastasized for 5 years.
18. Difficulty swallowing, or suffering from malabsorption syndrome, or other diseases
that are unable to absorb drugs through the intestine or conditions that affect the
absorption of BEBT-607.
19. Known active tuberculosis.
20. Patients with Gilbert syndrome or other diseases that may result in an increased
susceptibility to abnormal liver function tests during the study period.
21. Other situations judged by the investigator to be ineligible for inclusion.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Xiangya Hospital of Central South University
Address:
City:
Changsha
Zip:
410008
Country:
China
Status:
Recruiting
Contact:
Last name:
Zhenhua Liu
Phone:
+86-18922136143
Email:
zhliu@bebettermed.com
Start date:
September 4, 2023
Completion date:
June 2025
Lead sponsor:
Agency:
BeBetter Med Inc
Agency class:
Industry
Collaborator:
Agency:
Xiangya Hospital of Central South University
Agency class:
Other
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/NCT06117371
