Trial Title:
A Study of YL-17231 in Patients With Advanced Solid Tumors
NCT ID:
NCT06078800
Condition:
Advanced Solid Tumor
Conditions: Official terms:
Neoplasms
Conditions: Keywords:
Nonsmall-cell lung cancer（NSCLC）
Colorectal cancer（CRC）
Pancreatic carcinoma
KRAS mutation
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Sequential Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
YL-17231
Description:
After a screening period of approximately 14 days, eligible patients will receive oral
YL-17231 once or twice daily until documented disease progression, unacceptable AEs,
intercurrent illness preventing further administrations of study treatment,
investigator's decision to withdrawal, the patient's consent of withdrawal, pregnancy, or
for administrative reasons. Following the end of treatment, patients will continue to be
followed for safety for 30 days. Patients who permanently discontinue study treatment for
reasons other than disease progression will have post-treatment follow-up for disease
assessment until start of new anticancer treatment, patient's consent of withdrawal, lost
to follow-up, death, or until the Sponsor stops the study, whichever comes first.
Arm group label:
YL-17231
Other name:
Pan-KRAS Inhibitor YL-17231
Summary:
This is a phase 1 open label multicenter study to evaluate the maximum tolerance, safety,
tolerance and PK of oral YL-17231 in patients with advanced solid tumors with KRAS
mutation, so as to confirm the recommended phase 2 dose of YL-17231 and obtain the
preliminary efficacy information of patients with advanced solid tumors with KRAS
mutation.
Detailed description:
The study will be conducted in China to provide safety, efficacy and PK data. A dose
escalation part 1 will be conducted to determine the MTD, DLTs, and part 2 will confirm
the safety/tolerability of the recommended Phase 2 dose (RP2D), of YL-17231 given twice
daily, in patients with advanced solid tumors to obtain preliminary efficacy information.
PK samplings at single dose stage Day 1 and at steady-state conditions (Cycle 1, Day 14)
will be performed.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
The patients must meet all the following inclusion criteria to be eligible for enrollment
in this trial:
1. Age between 18 and 75 years (inclusive), with no gender restriction.
2. Locally advanced or metastatic solid tumors diagnosed histologically and genomically
confirmed with KRAS mutation, excluding patients with a clear KRAS wild-type test
report in the case of pancreatic cancer.
A. For patients with NSCLC, previous treatment failure based on platinum-based
first-line therapy; B. For patients with colorectal cancer, previous experience with
at least two lines of systemic therapy (patients with colorectal cancer and high
microsatellite instability should have received PD-1 or PD-L1 therapy if clinically
applicable); C. For patients with solid tumors other than NSCLC or colorectal
cancer, at least one prior systemic treatment is required.
3. In the dose escalation phase, measurable or non-measurable tumor lesions are
acceptable based on RECIST1.1 criteria; in the dose expansion phase, at least one
measurable tumor lesion is required.
4. ECOG performance status (PS) of 0-1.
5. Estimated life expectancy of ≥3 months.
6. Good organ function levels:
- Absolute neutrophil count (ANC) ≥1.5×109/L;
- Platelet count (PLT) ≥100×109/L;
- Hemoglobin (Hb) ≥90g/L (no blood transfusion within 14 days before screening);
- Total bilirubin (TBIL) ≤1.5 times the upper limit of normal;
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 times
the upper limit of normal (≤5.0 times the upper limit of normal for patients
with liver metastasis);
- Serum creatinine (Cr) ≤1.5 times the upper limit of normal or creatinine
clearance ≥50ml/min;
- Left ventricular ejection fraction (LVEF) ≥50%;
- Fridericia-corrected QT interval (QTcF) <450ms.
7. Washout period of ≥4 weeks for macromolecular agents and intravenous chemotherapy
drugs, and ≥2 weeks for oral fluoropyrimidine and small molecule targeted drugs.
8. Fertile males and females must agree to use medically approved contraceptive
measures during the study period and for 6 months following the last administration
of the study drug.
9. Women of childbearing potential must have a negative pregnancy test within 7 days
prior to the first administration of the study drug; patients must not be
breastfeeding, and if the subject has already ceased breastfeeding at the time of
study entry, breastfeeding must have been discontinued from the day of the first
administration of the study drug till at least 30 days after last administration of
the study drug .
10. No previous treatment with investigational drugs within 1 month prior to
participation in this trial.
11. High compliance and willingness to complete the trial as assessed by the
investigator, and ability to adhere to the study protocol.
12. Voluntary participation in this clinical trial, understanding of the study
procedures, and ability to provide written informed consent.
Exclusion Criteria:
Patients with any of the following conditions are not eligible for enrollment in this
study:
1. Uncontrollable third-space effusion (such as large amounts of pleural or ascitic
fluid).
2. Grade 3 or 4 gastrointestinal bleeding or variceal bleeding requiring transfusion,
endoscopy, or surgical intervention within the past 3 months.
3. Previous diagnosis of other malignancies within the past five years, except for
basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or cured in
situ cervical cancer.
4. Inability to swallow, chronic diarrhea, or intestinal obstruction that could affect
medication intake and absorption.
5. History of significant neurological or psychiatric disorders.
6. Active hepatitis B (positive for hepatitis B surface antigen and/or hepatitis B core
antibody with HBV-DNA ≥103 copies/mL or ≥200 IU/mL) or hepatitis C (positive for
hepatitis C virus antibody and/or HCV-RNA).
7. History of immunodeficiency, including positive HIV test, acquired or congenital
immunodeficiency disorders, organ transplantation, or allogeneic bone marrow
transplantation.
8. Major surgical procedures (excluding biopsy) within the past 4 weeks prior to the
first administration of the study drug, significant trauma, or the need for elective
surgery during the study period, or radical radiotherapy within the past 4 weeks
prior to the first administration of the study drug.
9. Moderate or severe cardiac diseases:
- Myocardial infarction, angina, III/IV congestive heart failure, pericardial
effusion, or uncontrolled severe hypertension (up to 150/90 mmHg or below)
within the past 6 months prior to the first administration of the study drug;
- Clinically significant electrocardiogram abnormalities, such as symptomatic or
persistent atrial or ventricular arrhythmias, second or third-degree
atrioventricular block, bundle branch block, or ventricular hypertrophy;
- Significant abnormalities on echocardiography, such as moderate or severe
valvular dysfunction, assessed based on institutional lower limits; patients
with minimal or mild valve regurgitation (tricuspid, pulmonary, mitral, or
aortic) can be included in this study;
- Various factors that may increase the risk of QTcF prolongation or cardiac
arrhythmia events, such as hypokalemia, congenital long QT syndrome, or
concomitant use of drugs that may prolong the QT interval.
10. Untreated brain metastases that meet one or more of the following criteria:
- Requiring corticosteroids or dehydration treatment (excluding the use of
antiepileptic drugs after surgery or radiotherapy);
- Presence of clinically significant symptoms;
- Tumor stability after radiotherapy or surgery lasting no longer than 4 weeks.
Asymptomatic or controlled stable patients with treated brain metastases are
eligible for enrollment.
11. Unresolved treatment-related toxicity greater than Grade 1 according to CTCAE 5.0 at
the start of study treatment (alopecia excluded).
12. Medical conditions that, in the opinion of the investigator, pose a serious risk to
patient safety or could interfere with the patient's ability to complete the study,
such as uncontrolled diabetes, thyroid disease, interstitial lung disease, severe
active infections, or uncontrolled chronic infections, Child-Pugh Class B or C liver
cirrhosis.
13. Other reasons deemed unsuitable for participation in this study by the investigator.
Gender:
All
Minimum age:
18 Years
Maximum age:
75 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Sun Yat-sen University Cancer Center
Address:
City:
Guangzhou
Country:
China
Status:
Recruiting
Contact:
Last name:
Xu Ruihua, PhD
Email:
xurh@sysucc.org.cn
Start date:
September 28, 2023
Completion date:
December 2025
Lead sponsor:
Agency:
Shanghai YingLi Pharmaceutical Co. Ltd.
Agency class:
Industry
Source:
Shanghai YingLi Pharmaceutical Co. Ltd.
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06078800
