Trial Title:
A Phase I Study of BR115 for Injection Alone in Subjects With Advanced Solid Malignancies
NCT ID:
NCT06388902
Condition:
Advanced Solid Malignancies
Conditions: Official terms:
Neoplasms
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Not yet recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
BR115 for injection
Description:
BR115 for injection will be administered by subcutaneous injection, two doses at the
first week of treatment, followed by once per week until intolerable toxicity, disease
progression, pregnancy, withdrawal of informed consent, death, study discontinuation or
withdrawal from the study. The dose of each administration will be calculated based on
the weight measured prior to such administration. The dosing regimen (dosing frequency
and interval) for subsequent study may be adjusted based on prior data.
Arm group label:
BR115
Summary:
This is a Phase I, multicenter, open-label, single-arm and first-in-human clinical study
of BR115 for injection. The study objectives are to evaluate the safety, tolerability,
pharmacokinetic profile, anti-tumor activity and immunogenicity of BR115 for injection in
patients with advanced solid malignancies.
Patients will receive two doses at the first week of treatment, followed by once per week
until intolerable toxicity, disease progression, pregnancy, withdrawal of informed
consent, death, study discontinuation, or withdrawal from the study.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- (1) Subjects who voluntarily sign the informed consent form, understand the nature,
objectives, and procedure of the study and are able to complete the study according
to the protocol; (2) ≥18 years of age (based on the date of signing the informed
consent form); (3) In Phase Ia: patients must have advanced solid tumors confirmed
by histopathology and/or cytology, the expression of HER2 was confirmed by the
laboratory（IHC3+、or IHC2+ and FISH+、or IHC2+ and ISH-、or IHC1+）who have failed to
respond to standard-of-care (disease progression after treatment) or who could not
tolerate standard-of-care, or who could not obtain effective standard-of-care or for
whom there was no effective standard-of-care available; (Note: the patient
population and inclusion criteria in phase Ib will be determined according to the
data of phase Ia); (4) According to RECIST v1.1 (Response Evaluation Criteria in
Solid Tumors), there is at least 1 measurable lesion; (5) Eastern Cooperative
Oncology Group (ECOG) Status 0 to 1; (6) Adequate organ and bone marrow function (no
treatment with cells, growth factors, or transfusions within 14 days prior to the
first administration), as defined below:
1. Hematology: absolute neutrophil count (ANC) ≥ 1.0 × 109/L, platelet count (PLT)
≥ 100 × 109/L, hemoglobin (HGB) ≥ 80 g/L，the lymphocyte count is normal ≥ 0.8 ×
109/L;
2. Liver function: serum total bilirubin (TBIL) ≤ 1.5 × upper limit of normal
(ULN) (except for subjects with Gilbert syndrome, TBIL ≤ 2 × ULN in patients
with liver cancer or liver metastases), alanine aminotransferase (ALT) and
aspartate aminotransferase (AST) ≤ 2.5 × ULN (in patients with liver cancer or
liver metastases, ALT or AST ≤ 5 × ULN);
3. Renal function: creatinine (Cr) ≤ 1.5 × ULN or creatinine clearance (CrCL)
(based on Cockcroft-Gault equation) ≥ 60 mL/min;
4. Lung function：Vital capacity and forced expiratory volume in the first second
(FEV1) were > 65% of the normal predicted value, and diffusion capacity was >
55% of the normal predicted value； (7) Expected survival ≥ 12 weeks; (8) Female
subjects with fertility potential must test negative for serum human chorionic
gonadotropin (HCG) before they are enrolled in the study. Female subjects with
fertility potential or male subjects who have a female partner must agree to
maintain no pregnancy plan and take effective contraceptive measures such as
condoms from the signing of ICF to 6 months after the last dose of study drug;
females are considered fertile from menarche to menopause (at least 12 months
without menstruation) unless they are permanently infertile (through
hysterectomy, bilateral salpingectomy, or bilateral oophorectomy).
Exclusion Criteria:
- (1) Subjects who have previous hypersensitivity to BR115 or known hypersensitivity
to any component or excipient of the study drug; (2) Subjects who have any active
infections, including bacterial, viral, fungal, mycobacterial, parasitic, or other
infections (excluding onychomycosis) , were present at the time of first
administration; (3) Subjects who have previous or current presence of two or more
primary tumors (excluding cured cervical carcinoma in situ, basal cell carcinoma, or
squamous cell carcinoma of the skin, and other tumors that have been stable for more
than 5 years after treatment); (4) Subjects who have symptoms of active central
nervous system metastases； (5) Subjects with serious cardiovascular and
cerebrovascular diseases and lung diseases, including but not limited to:
1. Stroke, intracranial hemorrhage, unstable angina pectoris, congestive heart
failure (NYHA class III-IV), myocardial infarction, severe arrhythmias (such as
sustained ventricular tachycardia and ventricular fibrillation), congenital
long QT syndrome, torsade de pointes, and symptomatic pulmonary embolism within
6 months before enrollment;
2. Uncontrolled hypertension (at least 2 consecutive measurements of systolic
blood pressure ≥ 160 mmHg or diastolic blood pressure ≥ 100 mmHg);
3. Echocardiogram (ECHO) or multigated acquisition scan (MUGA) shows left
ventricular ejection fraction (LVEF) < 50%;
4. During the screening period, the mean corrected (by Fridercia's formula) QT
interval on three consecutive electrocardiograms is prolonged (> 450 ms in
males and > 470 ms in females);
5. Subjects who have interstitial lung diseases, severe impaired lung function,
severe pulmonary fibrosis, radiation pneumonitis, and other lung diseases
assessed by the investigator as clinically significant; (6) (6)
Gastrointestinal disorders considered clinically significant by the
investigators (e.g. , including liver disease, bleeding, inflammation,
obstruction, intestinal obstruction, grade 1 diarrhea, jaundice, intestinal
paralysis, malabsorption syndrome, ulcerative colitis, inflammatory bowel
disease, or partial intestinal obstruction); (7) Subjects who have undergone
major surgery within 4 weeks prior to the first dose of study drug or are
expected to be performed during the study; (8) Subjects who have a history of
allogeneic organ transplantation or allogeneic hematopoietic stem cell
transplantation; (9) Subjects who have used strong inhibitors or substrates of
CYP3A4 and/or Pgp within 4 weeks before the first dosing or within 5 half-lives
of the used drug (whichever is shorter), or who have received anti-tumor
therapy or participated in other clinical studies and used other study drugs,
including chemotherapy, targeted therapy, immunotherapy, biotherapy (tumor
vaccines, cytokines, or growth factors for cancer control), etc.; or who have
received prepared slices of Chinese crude drugs or Chinese patent medicines as
anti-tumor treatment within 1 week before the first dose of study drug; (10)
Systemic immunosuppressants/agonists (drugs with longer half-lives) , such as
PD1, CTLA4,41BB, were used within 4 half-lives before the first administration;
(11) Subjects who have received radiation therapy, including abdominal
palliative stereotactic radiotherapy, within 4 weeks prior to the first dose of
study drug (non-abdominal palliative stereotactic radiotherapy within 2 weeks
prior to the first dose); (12) Toxicity of previous antineoplastic therapy does
not resolve to grade ≤ 1 as defined by NCI-CTCAE v5.0 (except for asymptomatic
abnormal laboratory findings considered by the investigator, such as elevated
ALP, hyperuricemia, elevated blood glucose, etc.; except for toxicity with no
safety risk determined by the investigator , such as alopecia, pigmentation,
etc.); (13) Subjects who have been vaccinated with a live vaccine within 4
weeks before the first dose, or who intend to be vaccinated with a live vaccine
during the study; (14) Subjects who have received more than 1 week of treatment
with systemic corticosteroids (methylprednisolone > 10 mg/day or an equivalent
dose of other similar drug) within 2 weeks prior to the first dose of study
drug; (15) Subjects who have used immunosuppressants within 2 weeks prior to
the first dose or once had active autoimmune diseases or had a prior history of
autoimmune diseases; (16) Subjects who test positive for Hepatitis B surface
antigen (HBsAg) with HBV DNA beyond the normal range; or subjects who test
positive for hepatitis B core antibody with HBV DNA beyond the upper limit of
normal, but do not agree to regular DNA testing during treatment and follow-up,
or do not agree to receive antiviral therapy; subjects who test positive for
hepatitis C virus (HCV) antibody and HCV RNA; subjects who are seropositive for
human immunodeficiency virus (HIV); subjects who have syphilis and need to
receive systemic treatment; (17) Subjects who are pregnant or breastfeeding;
(18) Subjects who are not eligible for enrollment by the investigator's
assessment.;
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Sun Yat-sen University Cancer Center
Address:
City:
Guangzhou
Zip:
510060
Country:
China
Contact:
Last name:
Rui Xu, MD
Phone:
86-20-87343468
Email:
ruihxu@163.com
Start date:
April 2024
Completion date:
December 2028
Lead sponsor:
Agency:
BioRay Pharmaceutical Co., Ltd.
Agency class:
Industry
Source:
BioRay Pharmaceutical Co., Ltd.
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06388902
