Trial Title:
A Phase l Study of By101298, an Oral DNA-PK Inhibitor, in Patients With Advanced Solid Tumors
NCT ID:
NCT06462716
Condition:
Solid Tumor, Adult
Conditions: Official terms:
Neoplasms
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
BY101298 Capsules
Description:
An oral DNA-PK Inhibitor
Arm group label:
BY101298
Summary:
BY101298 is an innovative DNA-dependent protein kinases (DNA-PK) highly selective small
molecule inhibitor. DNA-dependent protein kinases (DNA-PK plays a key role in the NHEJ
repair pathway to repair DNA double-strand breaks (DSBs).
Primary objective is to assess the safety and tolerability of BY101298 in patients with
advanced malignant solid tumors. The secondary Objectives are to characterize the
pharmacokinetic (PK) profile of BY101298 in patients with advanced malignant solid tumors
and to assess the preliminary efficacy of BY101298 in patients with advanced malignant
solid tumors.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Male or female patients, ≥ 18 and ≤ 75 years of age (inclusive at the time of
informed consent).
2. Diagnostic outcome:
Phase Ia: patients histologically or cytologically diagnosed advanced malignant
solid tumors who have failed, cannot tolerate, or refuse prior standard treatment
regimens. At least 1 measurable lesion per the Response Evaluation Criteria in Solid
Tumors (RECIST) v1.1 criteria.
3. Life expectancy ≥ 3 months.
4. Eastern Cooperative Oncology Group (ECOG) Performance Status 0 to 1.
5. Adequate organ and bone marrow function. Laboratory tests that meet the following
criteria within 7 days prior to the first dose of study treatment (without blood
transfusion, erythropoietin, recombinant human thrombopoietin or colony stimulating
factor therapy, renal replacement therapy, etc., within 28 days prior to the
screening examination):
Routine blood test:
Absolute neutrophil count (ANC) ≥ 1.5×109/L Platelets count (PLT) ≥ 100×109/L
Hemoglobin (Hb) ≥ 90 g/L
Hepatic function:
Total bilirubin (TBIL) ≤ 1.5×ULN Aspartate aminotransferase (AST) ≤ 2.5×ULN Alanine
aminotransferase (ALT) ≤ 2.5×ULN ALT and AST ≤ 5×ULN and TBIL ≤ 3×ULN for patients
with primary liver cancer, liver metastases, or Gilbert 's syndrome.
Renal function:
Creatinine clearance ≥ 50 mL/min (calculated according to Cockcroft-Gault formula).
Coagulation function:
International normalized ratio (INR) and activated partial thromboplastin time
(APTT) ≤ 1.5×ULN
6. Females and males of childbearing potential must agree to use appropriate methods of
contraception (hormonal/barrier method or abstinence) during the study and for 3
months after the last dose. Female subjects of childbearing potential must have a
negative serum pregnancy test within 7 days prior to administration.
Understand and be willing to sign written informed consent and be able to follow the
study protocol for treatment, visits, and other study procedures.
Exclusion Criteria:
- 1.Treated with DNA-PK inhibitors. 2.Patients who have received systemic
chemotherapy, traditional Chinese medicine for anti-tumor indications or other
anti-tumor drugs (including endocrine therapy, molecular targeted therapy,
immunotherapy, biological therapy, etc.) within 4 weeks or 5 half-lives (whichever
is longer) prior to the first dose of the study drug, or those who need to continue
receiving these drugs during the study, with the following three exceptions:
Receiving nitrosourea or mitomycin C, which needs more than 6 weeks from the last
dose.
Receiving extensive radiotherapy (> 30% of bone marrow radiation), which needs more than
8 weeks from the last radiotherapy.
History of palliative radiotherapy for bone metastases, which needs more than 2 weeks
from the last radiotherapy.
3.Major surgery (craniotomy, thoracotomy, or laparotomy) within 4 weeks prior to the
first dose of the study drug and surgery is scheduled during the study period.
4.Brain metastasis (except asymptomatic, stable for more than 4 weeks prior to the first
dose and not requiring steroid therapy for at least 4 weeks prior to the first dose, no
imaging findings of marked edema around the tumor lesion), presence of meningeal
metastasis or brainstem metastasis, or presence of spinal cord compression.
5.History of other malignancy within the past 5 years, except skin basal cell carcinoma,
skin squamous cell carcinoma, cervical carcinoma in situ, or other carcinomas in situ
which have undergone curative treatment and have had no recurrence within 5 years after
treatment.
6.Toxicities from prior antitumor therapy that have not recovered to CTCAE version 5.0
Grade 1 or less, except CTCAE (V5.0) Grade 2 peripheral neurotoxicity and alopecia of any
grade.
7.Serious or uncontrolled diseases as assessed by the investigator, including but not
limited to: Severe or uncontrolled diabetes (fasting blood glucose ≥ 10 mmol/L), poorly
controlled hypertension (systolic blood pressure ≥ 160 mmHg and/or diastolic blood
pressure ≥ 100 mmHg under standardized antihypertensive regimens), epilepsy, chronic
obstructive pulmonary disease, interstitial pneumonia, pulmonary interstitial fibrosis,
Parkinson 's disease, active bleeding, uncontrolled infection.
Cognitive dysfunction, history of psychiatric disorders, other uncontrolled concomitant
diseases, alcohol dependence, hormone dependence, or drug abuse.
History of immunodeficiency, including HIV antibody positive, other acquired or
congenital immunodeficiency disease, or history of organ transplantation.
HBsAg or HBcAb positive, and peripheral blood HBV DNA titer test ≥ 200 IU/mL or ≥ 1000
copies/mL or above the upper limit of normal value at the study site; HCV antibody test
positive, and HCV RNA test above the upper limit of normal value at the study site;
treponema pallidum-specific antibody positive.
Clinically serious gastrointestinal dysfunction that may compromise drug intake,
transport, or absorption. For example, inability to take oral medication, uncontrollable
nausea or vomiting, history of massive gastrointestinal resection, history of
gastrointestinal ulcer and gastrointestinal bleeding within 6 months prior to the first
dose, untreated recurrent diarrhea, untreated stomach disease requiring long-term use of
PPI acid suppressants, Crohn 's disease, ulcerative colitis, etc.
Prior thyroid dysfunction or inability to maintain thyroid function within normal limits
even with medical therapy.
8.Cardiac dysfunction, including any of the following: Myocardial infarction in past 6
months, heart failure classified as Class II/III/IV according to the New York Heart
Association (NYHA) Functional Classification, unstable angina pectoris, and unstable
arrhythmia.
Left ventricular ejection fraction LVEF < 50% shown by echocardiography. QT interval
corrected using Fridericia 's formula: QTcF > 470 msec (females), QTcF > 450 msec
(males).
9.Pregnant (positive pregnancy test prior to dosing) or lactating. 10.History of serious
hypersensitivity (e.g., anaphylactic shock) or hypersensitivity to excipients or other
ingredients associated with the study drug.
Other factors considered unsuitable for study enrollment by the investigator.
Gender:
All
Minimum age:
18 Years
Maximum age:
75 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Cancer Hospital Affiliated to Shandong First Medical University / Shandong Cancer Research Institute / Shandong Cancer Hospital
Address:
City:
Jinan
Zip:
250117
Country:
China
Status:
Recruiting
Contact:
Last name:
Jinming professor Yu, MD
Phone:
+8613806406293
Email:
13370582181@163.com
Contact backup:
Last name:
Yuping professor Sun, MD
Phone:
+86-531-67627158
Email:
13370582181@163.com
Start date:
April 25, 2023
Completion date:
June 30, 2025
Lead sponsor:
Agency:
Chengdu Baiyu Pharmaceutical Co., Ltd.
Agency class:
Industry
Source:
Chengdu Baiyu Pharmaceutical Co., Ltd.
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06462716
