Trial Title:
A Phase l Study of By101921, an Oral PARP7 Inhibitor, in Patients With Advanced Solid Tumors
NCT ID:
NCT06433726
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:
BY101921 tablets
Description:
An oral PARP7 Inhibitor
Arm group label:
BY101921
Summary:
BY101921 is a novel small molecule, being developed as a PARP7 inhibitor which acts on
the PARP7 catalytic subunit, for the treatment of solid tumors. PARP7 is a member of the
monoPARP family and involved in various biological processes such as gene expression,
protein degradation, and cellular stress response. The results of non-clinical studies
showed BY101921 was a potent inhibitor of PARP7 and had good selectivity.
The primary objective is to assess the safety and tolerability and MTD of BY101921 in
patients with refractory or metastatic solid tumors. This study will also evaluate
pharmacokinetic (PK) profile, preliminary anti-tumor activity, major metabolites and
biomarkers in patients with refractory or metastatic solid tumors.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Male or female patients ≥18 years and ≤75 years of age.
2. 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. Have a projected life expectancy of at least 3 months.
4. Eastern Cooperative Oncology Group Performance Status 0 or 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.
7. 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. Previously treated with PARP-7 inhibitors.
2. Treated with a potent CYP3A4 inhibitor or inducer within 2 weeks prior to the first
dose of study treatment.
3. Previous any treatment with of the following:
1. Systemic chemotherapy, other antitumor agents (including endocrine therapy,
macromolecular targeted therapy, immunotherapy, or biotherapy) within 4 weeks
or 5 half-lives prior to the first dose of study treatment, or who need to
continue receiving these agents during the study period;
2. Small molecule targeted therapy within 2 weeks or 5 half-lives prior to the
first dose of study treatment;
3. Anti-tumor traditional Chinese medicine or proprietary Chinese medicine
preparations prior to the first dose of study treatment;
4. Nitrosourea or mitomycin C within 6 weeks prior to the first dose of study
treatment;
5. Palliative radiation therapy within 2 weeks prior to the first dose of study
treatment;
6. Investigational drug within 4 weeks prior to the first dose of study treatment;
g Radical radiation therapy within 4 weeks prior to the first dose of study
treatment.
4. Major surgical intervention (excluding needle biopsy) within 28 days before study
drug administration, surgical wound has not fully healed or surgery is scheduled
during the study period.
5. 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.
6. 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.
7. 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.
8. Difficult-to-control pleural effusion, ascites, or pericardial effusion.etc,
requiring repeated drainage and considered unsuitable for study enrollment by the
investigator.
9. Serious or uncontrolled diseases as assessed by the investigator, including but not
limited to:
Severe or uncontrolled diabetes, 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.
10. 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).
11. Pregnant (positive pregnancy test prior to dosing) or lactating.
12. History of serious hypersensitivity (e.g., anaphylactic shock) or hypersensitivity
to excipients or other ingredients associated with the study drug.
13. Cannot follow the protocol to "avoid ingesting grapefruit , pomegranate, orange or
green lemon (juice/sauce made from these fruits as well) within 7 days before study
drug administration and throughout the BY101921 treatment period".
14. 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
Investigator:
Last name:
Jinming professor Yu, MD
Email:
Principal Investigator
Investigator:
Last name:
Yuping professor Sun, MD
Email:
Principal Investigator
Start date:
March 11, 2024
Completion date:
December 31, 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/NCT06433726
