Trial Title:
A Phase Ib/II Study of BY101298 , an Oral DNA-PK Inhibitor, Combined With Radiotherapy in Patients With Malignant Solid Tumors
NCT ID:
NCT06524804
Condition:
Solid Tumor, Adult
Conditions: Official terms:
Neoplasms
Study type:
Interventional
Study phase:
Phase 1/Phase 2
Overall status:
Recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Sequential 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 in combination with palliative radiotherapy
Intervention type:
Radiation
Intervention name:
palliative radiotherapy
Description:
Undergo palliative radiotherapy
Arm group label:
BY101298 in combination with palliative radiotherapy
Intervention type:
Drug
Intervention name:
BY101298 Capsules
Description:
An oral DNA-PK Inhibitor
Arm group label:
BY101298 in combination with curative radiotherapy
Intervention type:
Radiation
Intervention name:
curative radiotherapy
Description:
Undergo curative radiotherapy
Arm group label:
BY101298 in combination with curative radiotherapy
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). By inhibiting DNA-PK activity
to inhibit DSBs repair, BY101298 may synergistically improve the killing effect on tumor
cells, reduce the risk of local recurrence and metastasis, and improve the clinical
benefit of cancer patients when combing with radiotherapy.
Primary objective is to assess the safety and tolerability; RP2D. The secondary
Objectives are to characterize the pharmacokinetic (PK) profile of BY101298 and to assess
the preliminary efficacy.
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. histologically or cytologically diagnosed solid tumors with indications for
radiotherapy after evaluation by investigator (Radiotherapy sites are excluded for
patients with primary brain tumors and/or brain metastases). Radiotherapy techniques
could be IMRT, IGRT, VMAT or TOMO, except SBRT and SRS.
3. Cohort 1: Patients with locally advanced/advanced malignant solid tumors who will
receive radiotherapy for non-radical purposes, such as radiotherapy for
non-oligometastatic tumors.
4. Cohort 2: Radiotherapy for radical purposes [including, but not limited to,
radiotherapy for residual or oligofocal lesions with stable disease or partial
response (SD, PR) after systemic treatment, sequential chemoradiotherapy, or not
suitable for chemotherapy] with at least one measurable lesion present in the
radiation field according to RECIST 1.1 criteria, and radiotherapy dose following
each solid tumor radiotherapy guideline. The segmentation method is conventional
segmentation.
5. After obtaining RP2D doses in Phase Ib, extended studies were conducted in specific
indications in cohort 1 and Cohort 2, respectively.
6. Life expectancy ≥ 3 months (cohort 1), and ≥ 6 months (cohort 2).
7. The lesions outside the radiation field are tended to be stabilized evaluated by the
investigator.
8. Eastern Cooperative Oncology Group (ECOG) Performance Status 0 to 1. (If the
symptoms are caused by tumor lesions in the radiotherapy field, ECOG score 0-2
points).
9. 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 14 days prior to the
screening examination).
10. 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. Potential risks of perforation, bleeding, or other unacceptable risks after
treatment evaluated by the investigator.
3. Radiotherapy sites are primary brain tumors and/or brain metastases.
4. Previous treatment with any of the following:
1. 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.
2. Received radiation therapy in the planned radiotherapy field (re-course and
multi-course same-site radiotherapy should be excluded in principle).
3. The patient has previously received radiotherapy at another site, unless there
is no potential risk based on OAR exposure evaluated by the investigator.
4. Received chinese troditional medicine (Chinese patent medicine) with antitumor
indications within 2 weeks prior to initial administration of the
investigational drug.
5. 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.
6. 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.
7. Concomitant with other malignancies that may affect the patient's expected life
expectancy.
8. Have undergone bone marrow transplants and/or organ transplants, including
allogeneic stem cell transplants.
9. 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, and other toxicity that has no safety risk evaluated by the
investigator.
10. Patients with third lacunar effusion (such as large pleural effusion, ascites, or
pericardial effusion) which is difficult to control and requires repeated drainage.
11. Serious or uncontrolled diseases as assessed by the investigator, including but not
limited to:
1. 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.
2. Cognitive dysfunction, history of psychiatric disorders, other uncontrolled
concomitant diseases, alcohol dependence, hormone dependence, or drug abuse.
3. History of immunodeficiency, including HIV antibody positive, other acquired or
congenital immunodeficiency disease, or history of organ transplantation.
4. 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.
5. 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.
6. Prior thyroid dysfunction or inability to maintain thyroid function within
normal limits even with medical therapy.
12. Cardiac dysfunction, including any of the following:
1. 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.
2. Left ventricular ejection fraction LVEF < 50% shown by echocardiography.
3. QT interval corrected using Fridericia 's formula: QTcF > 470 msec (females),
QTcF > 450 msec (males).
13. Pregnant (positive pregnancy test prior to dosing) or lactating.
14. History of serious hypersensitivity (e.g., anaphylactic shock) or hypersensitivity
to excipients or other ingredients associated with the study drug.
15. Received live attenuated vaccine within 28 days prior to the first dose.
16. Other factors considered unsuitable for study enrollment by the investigator.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
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
Investigator:
Last name:
Jinming professor Yu, MD
Email:
Principal Investigator
Investigator:
Last name:
Yuping professor Sun, MD
Email:
Principal Investigator
Start date:
May 15, 2024
Completion date:
June 30, 2026
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/NCT06524804
