Trial Title:
VIC-1911 Combined With Osimertinib for EGFR -Mutant Non-small Cell Lung Cancer
NCT ID:
NCT05489731
Condition:
Advanced Non-small Cell Lung Cancer
Conditions: Official terms:
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Osimertinib
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Single Group Assignment
Intervention model description:
In the dose escalation phase, a total of 2 groups were planned, and 6-12 patients were
expected to be enrolled. In the expansion phase, two cohorts are planned, with each
cohort expanding to 20-30 patients, and approximately 40-60 patients are expected to be
enrolled. A total of 46 to 72 patients were enrolled in this phase I trial
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
VIC-1911
Description:
VIC-1911 tablets for oral administration
Arm group label:
Dose escalation phase-Dose group 1 VIC-1911 Tablets with Osimertinib Mesylate Tablets
Arm group label:
Dose escalation stage - Dose group 2 VIC-1911 Tablets with Osimertinib Mesylate Tablets
Arm group label:
Dose expansion phase VIC-1911 Tablets with Osimertinib Mesylate Tablets
Intervention type:
Drug
Intervention name:
Osimertinib Mesylate Tablets
Description:
Osimertinib tablets for oral administration
Arm group label:
Dose escalation phase-Dose group 1 VIC-1911 Tablets with Osimertinib Mesylate Tablets
Arm group label:
Dose escalation stage - Dose group 2 VIC-1911 Tablets with Osimertinib Mesylate Tablets
Arm group label:
Dose expansion phase VIC-1911 Tablets with Osimertinib Mesylate Tablets
Other name:
TAGRISSO
Summary:
This is a nonrandomized, open phase I dose escalation and extension clinical study
designed to evaluate Aurora A inhibitor VIC-1911 tablets in combination with oxitinib in
Chinese patients with advanced non-small cell lung cancer The safety, tolerability,
pharmacokinetic characteristics and preliminary antitumor efficacy were analyzed.
The entire study included the screening period (28 days prior to initialadministration of
the investigational drug) and the treatment period (Cycle) EoT is defined as disease
progression or intolerable toxicity or premature withdrawal Out]) and the safety
follow-up period (28 days after EoT). During dose increments and expansions, subjects
followed Safety assessment, PK blood collection, imaging examination and efficacy
assessment were performed during the visit plan. Observation subject The safety,
tolerability, and occurrence of DLT until disease progression, occurrence of intolerable
toxicity, Death, withdrawal of informed consent, loss of follow-up or termination of the
study by the sponsor shall prevail.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Voluntarily participate in clinical research, sign written informed consent, and be
able to abide by clinical visits and research Relevant procedures;
2. Male or female patients aged 18-75 (including boundary value) when signing the
informed consent form;
3. NSCLC with advanced EGFR mutation positive [exon 19 deletion (19del) and exon 21
L858R (21l858r) point mutation] confirmed by cytology or histology A. only
applicable to the dose increasing stage: after receiving the first / second
generation EGFR-TKI treatment failure T790M mutation negative or third-generation
EGFR-TKI treatment failed, and then received platinum containing dual drug
chemotherapy Terminal NSCLC patients after failure; B. only applicable to the
expansion phase: (1) queue 1: after the treatment failure of the first / second
generation EGFR-TKI NSCLC patients with T790M mutation positive; (2) Cohort 2: NSCLC
patients who failed to receive three generations of EGFR-tki treatment;
4. According to RECIST 1.1 standard, patients must have a passing shadow Measurable
lesions assessed by imaging examination;
5. The EC0G score is 0 or 1;
6. Estimated survival time ≥ 3 months;
7. Bone marrow reserve and organ function level within 7 days before administration
must meet the following requirements:
1. Bone marrow reserve: hemoglobin (HB) ≥ 9.0 g/dl, absolute neutrophil count
（ANC）≥ 1.5 × 109/l, platelet (PLT) ≥ 100 × 109/l, opened during the study
treatment period Blood transfusion (whole blood, platelets or red blood cells)
is prohibited 1 month before the start;
2. Coagulation function: international normalized ratio (INR) ≤ 1.5 × Upper normal
value (ULN), active Partial prothrombin time (APTT) ≤ 1.5 × ULN；
3. Liver function: aspartate aminotransferase (AST) and alanine in the absence of
liver metastasis Transaminase (ALT) ≤ 2.5 × ULN； In case of liver metastasis,
AST and alt ≤ 5.0 × ULN；Total bilirubin in serum (TBIL) ≤ 1.5 × ULN (patients
known to have Gilbert syndrome Only when total bilirubin ≤ 3 × ULN, direct
bilirubin ≤ 1.5 × In the case of ULN, it will be Consider);
4. Renal function: creatinine ≤ 1.5 × ULN or creatinine clearance ≥ 40 ml/min
(according to Cockcroft-Gault formula);
5. Cardiac function: left ventricular ejection fraction (LVEF) ≥ 50%; ECG is
basically normal,QT interval (QTCF) corrected by fridericia formula: male ≤ 450
ms, female ≤ 470 ms；
8. Qualified patients (male and female) with fertility must agree to give drugs during
the trial or at the end of the trial Use reliable contraceptive methods (hormone or
barrier method or abstinence) with their partners for at least 6 months Etc.); Women
of childbearing age (refer to the appendix of the text for the definition) within 7
days before the first use of the investigational drug The pregnancy test must be
negative.
Exclusion criteria：
1. Known allergy to, or hypersensitivity to, VIC-1911, osimertinib, or any of the
excipient ingredients
2. Subject has previously discontinued osimertinib due to toxicity or other safety
events Interstitial lung disease/non-infectious pneumonia; Symptoms or signs of
severe arrhythmia with prolonged QTc interval; Symptomatic congestive heart failure
3. Other side effects caused by previous treatment did not alleviate to CTCAE≤ grade 1,
alopecia or otherwise
4. A history of ocular disease was present, and the patient had occlusion of central or
branch retinal arteries or veins with visual acuity Significant decline, or a
history of visual impairment due to other retinal diseases as determined by an
ophthalmologist or Performance
5. The following infectious diseases are known to be active, such as:
Human immunodeficiency virus antibody (HIV-AB) positive; Hepatitis B surface antigen
(HBsAg) positive and HBV-DNA exceeding the upper limit of normal value; Hepatitis C
virus antibody (HCV-AB) positive and HCV RNA positive
6. Other active infections requiring intravenous antibiotics within 7 days before
administration;
7. Use of potent CYP inducer 28 days before administration or within 5 half-lives of
the drug, whichever is longer A guide or inhibitor;
8. Had undergone a major surgical procedure within 28 days prior to drug administration
or was expected to require a major procedure during the trial Surgery;
9. Received the latest antitumor therapy (chemotherapy, targeted therapy, radiotherapy,
immunotherapy, biological therapy) Therapy or endocrine therapy), less than 5
half-lives after or after the first administration of the drug Less than 28 days
(whichever is longer). Had received the drug within 14 days before the first dose
with definite resistance The effect of traditional Chinese medicine on tumor;
10. A history of serious cardiovascular and cerebrovascular diseases, including but not
limited to:
uncontrolled hypertension (systolic blood pressure >160 mmHg or shu) after standard
clinical treatment Tension >100 mmHg for more than 4 weeks); I have severe cardiac
rhythm or conduction abnormalities, such as ventricular arrhythmias that require
clinical intervention, Degree II-III atrioventricular block, etc Patients with grade
III-IV cardiac insufficiency according to New York Heart Association (NYHA) criteria
Any arterial thromboembolic event, including but not limited to myocardial
infarction, occurred within 6 months prior to dosing Plug, transient ischemic
attack, unstable angina pectoris or other grade 3 or above cardiovascular and
cerebrovascular disease Events; Any factor that increases the risk of prolonged QTc
intervals or arrhythmias: e.g., heart failure, hypokalemia Haemaemia, congenital
long QT syndrome, or the use of anything known to prolong the QT interval
Concomitant drugs (see Appendix of the main text for details), except antibiotics
used to prevent or treat infection;
11. Parenchymal or meningeal metastases with clinical symptoms were not eligible for
inclusion as judged by the investigator. Such as Previous systemic and radical brain
metastases therapy (radiotherapy or surgery) proved stable on imaging It has been
maintained for at least 28 days and has stopped systemic hormone therapy for more
than 14 days without clinical symptoms Is allowed to enter the group;
12. Suffers from hematological malignancies;
13. Other malignant tumors have been diagnosed within 5 years before the first use of
the study drug; Effectively treated skin Basal cell carcinoma, squamous cell
carcinoma of the skin, and/or effectively resected cervical cancer in situ and/or
breast Except the cancer;
14. Inability to swallow medication;
15. Gastrointestinal diseases that may affect the absorption or tolerability of the
trial drug, such as refractory or screening CTCAE> grade 2 gastrointestinal symptoms
(e.g., nausea, vomiting, diarrhea, etc.);
16. Patients with difficulty in venous blood collection;
17. Women who have a positive pregnancy test or are breastfeeding during the screening
period;
18. Administration of an investigational drug that has undergone clinical trials of
other drugs within 28 days prior to administration;
19. Previous treatment with other Aurora kinase inhibitors;
20. Patients with a history of blood donation or blood loss of more than 400 mL 3 months
before screening;
21. Anything else that, in the opinion of the investigator, may affect the subject to
provide informed consent or follow the protocol Circumstances, or the subject's
participation in the trial may affect the results of the trial or their own safety.
Gender:
All
Minimum age:
18 Years
Maximum age:
75 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Zhangli
Address:
City:
Guangdong
Country:
China
Status:
Recruiting
Contact:
Last name:
li zhang, professor
Start date:
September 21, 2022
Completion date:
April 24, 2024
Lead sponsor:
Agency:
Jiesi Yingda Pharmaceutical Technology (Suzhou) Co., Ltd.
Agency class:
Other
Source:
Jiesi Yingda Pharmaceutical Technology (Suzhou) Co., Ltd.
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05489731
