Trial Title:
A Clinical Study Evaluating the Safety, Tolerability, Pharmacokinetic Characteristics, and Preliminary Efficacy of the Combination of BAT8008 With BAT1308 in Patients With Advanced Solid Tumors
NCT ID:
NCT06341114
Condition:
Advanced Solid Tumors
Conditions: Official terms:
Neoplasms
Study type:
Interventional
Study phase:
Phase 1/Phase 2
Overall status:
Recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
BAT8008 injection
Description:
BAT8008 for injection is a sterile, preservative-free lyophilized powder packaged in
vials, with each vial containing 100 mg,Prior to infusion, reconstitute with 5
milliliters of sterile water for injection. After reconstitution, a clear to slightly
opalescent, colorless to pale yellow solution with a final concentration of 20 mg/mL can
be obtained.
Arm group label:
Co-administration of BAT8008 and BAT1308.
Intervention type:
Drug
Intervention name:
BAT1308 injection
Description:
One vial of 4 mL of concentrate contains 100 mg of BAT1308
Arm group label:
Co-administration of BAT8008 and BAT1308.
Summary:
The study, led by Zhejiang Cancer Hospital and sponsored by Bio-Thera Solutions, Ltd., is
an exploratory multicenter, open-label phase Ib-II clinical trial evaluating the safety,
tolerability, pharmacokinetic characteristics, and preliminary efficacy of the
combination of BAT8008 with BAT1308 in patients with advanced solid tumors.
This study aims to explore the safety, tolerability, and pharmacokinetic characteristics
of BAT8008 combined with BAT1308 in patients with advanced solid tumors, determine the
maximum tolerated dose (MTD), provide recommended doses and reasonable dosing regimens
for subsequent clinical studies, and preliminarily evaluate the antitumor efficacy.
The study is divided into two stages. The first stage will use a "3+3" dose escalation
design to explore the safety and tolerability of the investigational drugs. In the second
stage, based on the preliminary safety and efficacy results from the first stage,
appropriate doses and tumor types will be selected for expansion studies within the
safety dose range to further investigate the safety and clinical efficacy of
BAT8008+BAT1308 and provide evidence for subsequent clinical studies.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Age ≥ 18 years old, gender not specified;
2. Voluntary signing of the informed consent form;
3. Must be pathologically diagnosed by histology or cytology, with standard treatment
failure or absence of standard treatment, intolerance to standard treatment, or
refusal of standard treatment for advanced or metastatic epithelial solid tumor
patients. Expanded Research Phase: Divided into two cohorts (the sponsor may expand
or delete cohorts of tumor types based on real-time study results): Cohort A:
Locally advanced or metastatic triple-negative breast cancer diagnosed by histology
or cytology, and subjects who cannot be cured by radical resection or radiotherapy,
and have used at least one systemic chemotherapy regimen for advanced or metastatic
disease. Cohort B: Other advanced or metastatic epithelial solid tumor patients who
are intolerant or refuse standard treatment, prioritizing the following types:
non-squamous non-small cell lung cancer, gastric adenocarcinoma, esophageal cancer,
small cell lung cancer, cervical cancer, and head and neck squamous cell carcinoma.
4. According to RECIST 1.1 criteria, there must be evaluable tumor lesions in the dose
escalation phase, and at least one measurable tumor lesion in the dose expansion
phase;
5. Eastern Cooperative Oncology Group (ECOG) performance status score required is 0 or
1;
6. Investigator-assessed expected survival period ≥ 12 weeks;
7. Must have sufficient organ and bone marrow reserve function, defined as follows:
Hematology (no blood transfusions, hematopoietic growth factors, or drugs to correct
blood cell counts within 14 days prior to first dose):
Absolute neutrophil count (ANC) ≥ 1.5 × 10^9 /L Platelet count ≥ 90 × 10^9 /L
Hemoglobin ≥ 90 g/L
Coagulation:
International normalized ratio (INR) and activated partial thromboplastin time
(APTT) ≤ 1.5×ULN (for patients not receiving anticoagulation therapy) Patients
receiving oral anticoagulant therapy with an INR of 2~3 can be included
Liver function:
Total bilirubin (TBIL) ≤ 1.5×ULN For liver cancer or liver metastases, ≤2×ULN
Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5×ULN For
liver cancer or liver metastases, ≤5×ULN
Renal function:
Serum creatinine ≤ 1.5×ULN or estimated glomerular filtration rate > 50 ml/min
(using Cockcroft-Gault or modified MDRD formula, see appendix) Urine protein:
Urinalysis suggests urine protein < 2+ or urine protein quantification < 1g
8. Female patients of childbearing potential must have a negative serum pregnancy test
within 7 days before the first dose and be willing to use effective contraception
methods during the study period until 6 months after the last dose; male patients
must agree to use effective contraception methods during the study period until 6
months after the last dose; postmenopausal women must have been amenorrheic for at
least 12 months to be considered not of childbearing potential;
9. Willing to provide past archived or fresh tumor tissue samples (if there is no
archived tumor tissue in the past, and the investigator assesses that there is a
significant risk in obtaining fresh or metastatic tumor tissue specimens, exemption
may be granted). Immunohistochemical confirmation of PDL1 and Trop2 expression
levels is not required before enrollment, but the sponsor requires the collection of
biopsy or archived tumor tissue samples to determine PDL1 and Trop2 expression
levels;
10. Able to understand the requirements of the trial, willing, and able to comply with
the trial and follow-up arrangements.
Exclusion Criteria：
1. Within the first 4 weeks prior to the initial administration of the investigational
drug, having received experimental drug therapy or participated in clinical studies
of medical devices.
2. Within the first 4 weeks prior to the initial administration of the drug, having
undergone chemotherapy, curative radiotherapy (palliative radiotherapy should be
completed within 2 weeks prior to the initial drug administration), biological
therapy, endocrine therapy, immunotherapy, or other anti-tumor treatments; 2) For
fluoropyrimidine drugs and small molecule targeted drugs, within 2 weeks prior to
the initial administration of the investigational drug or within 5 half-lives of the
drug (whichever is longer); 3) Within 42 days prior to the initial administration of
the investigational drug for nitrosourea drugs or mitomycin C.
3. Having received, within 1 week prior to drug administration, traditional Chinese
medicine or treatment explicitly indicated in the drug instructions approved by the
NMPA for its anti-tumor functions, or having a clear record in medical history of
herbal treatment for anti-tumor purposes.
4. Prior anti-tumor therapy resulting in adverse events (AEs) (CTCAE 5.0) still at >
Grade 1 before the initial administration of the investigational drug, excluding
toxicities judged by the investigator to pose no safety risk, such as alopecia,
Grade 2 peripheral neuropathy, etc.
5. Needing major surgery within the first 4 weeks prior to the initial administration
of the investigational drug (excluding procedures for diagnosis) or anticipated
major surgery during the study period.
6. Patients who have previously received Trop2-ADC with small molecule toxins that are
topoisomerase I inhibitors.
7. Having experienced ≥ Grade 3 immune-related adverse events (irAEs) in the past or
having discontinued immunotherapy due to irAEs of any grade.
8. Individuals with a history of allogeneic cell or solid organ transplantation.
9. Patients with primary central nervous system tumors or symptomatic central nervous
system metastases, a history of or currently present meningeal metastases, or a
history of seizures. If brain metastases are stable after treatment and there are no
new lesions at least 4 weeks before medication, or if asymptomatic lesions are
detected for the first time within 4 weeks and the investigator determines disease
stability, or if the investigator decides to discontinue corticosteroid treatment 7
days before the initial administration of the investigational drug, then it is
allowed.
10. Any other active malignant tumors within 5 years before the initial administration
of the drug, except for locally cured tumors (such as basal cell carcinoma, squamous
cell carcinoma of the skin, superficial bladder cancer, or ductal carcinoma in situ
of the breast).
11. Occurrence of the following cardiovascular diseases within 6 months before the
initial administration of the drug: symptomatic heart failure of New York Heart
Association (NYHA) class 2 or higher, left ventricular ejection fraction (LVEF)
<50%, unstable arrhythmias or unstable angina, myocardial infarction requiring
treatment, pulmonary embolism, uncontrolled hypertension (defined in this protocol
as systolic blood pressure >160mmHg and/or diastolic blood pressure >100mmHg despite
optimal antihypertensive therapy, and assessed by the investigator to have clinical
significance), QTcF >480ms on 12-lead electrocardiogram (QTcF calculated using the
Fridericia correction formula).
12. Presence of any other severe underlying diseases (e.g., Gilbert's syndrome, poorly
controlled diabetes, active peptic ulcer, unstable controlled seizures,
cerebrovascular events/gastrointestinal bleeding within 3 months before the initial
administration of the drug, coagulation disorders with severe symptoms or signs), as
judged by the investigator to potentially affect the subject's participation in the
study, treatment, and follow-up, affect subject compliance, or potentially lead to
occurrences of drug-related complications in the subjects.
13. History of non-infectious pneumonia/pulmonary inflammation requiring glucocorticoid
treatment, current interstitial lung disease (ILD), or subjects in the screening
period with suspected ILD/pulmonary inflammation that cannot be ruled out by imaging
examinations.
14. Patients with a history of autoimmune diseases (except for autoimmune thyroid
diseases and type I diabetes that can be treated with hormone replacement therapy).
15. Received systemic corticosteroids (prednisone > 10mg/day or equivalent) or other
immunosuppressive agents within 14 days prior to the initial use of the
investigational drug; exceptions include the following: use of topical, ocular,
intra-articular, intranasal, or inhaled corticosteroids, short-term prophylactic use
of corticosteroids (duration not exceeding 2 weeks, e.g., for contrast allergy
prophylaxis).
16. Untreated or actively treated tuberculosis subjects, including but not limited to
pulmonary tuberculosis; subjects who have undergone standard anti-tuberculosis
treatment and have been confirmed by the investigator to be cured may be included.
17. Experienced severe infection within 4 weeks prior to the initial administration of
the drug or active infection within 2 weeks.
18. Subjects with the following infectious diseases: Human Immunodeficiency Virus (HIV)
infection; active Hepatitis B Virus infection [Hepatitis B Surface Antigen (HBsAg)
positive, with Hepatitis B Virus Deoxyribonucleic Acid (HBV-DNA) > 200 IU/ml or 10^3
copies/ml or within the upper limit of normal value determined by the study center];
Hepatitis C Virus infection [HCV antibody and Hepatitis C Virus Ribonucleic Acid
(HCV-RNA) positive]; positive syphilis treponemal antibody and RPR/TRUST positive.
19. Newly diagnosed thromboembolic events requiring treatment within 6 months (patients
with stable lower extremity deep vein thrombosis or port-related thrombosis are
allowed to be included).
20. Difficult-to-control pleural effusion, pericardial effusion, or ascites requiring
repeated drainage surgery (monthly or more frequently).
21. Known hypersensitivity reaction or delayed allergic reaction to any component of the
investigational drug.
22. Known occurrence of ≥ Grade 3 allergic reactions to macromolecular protein
preparations/monoclonal antibodies.
23. History of mental illness, substance abuse, alcoholism, or drug abuse that may
affect trial results.
24. Pregnant or lactating women or individuals planning to conceive.
25. Other conditions deemed inappropriate for participation in this trial by the
investigator.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Song ZhengBo
Address:
City:
Hangzhou
Zip:
310005
Country:
China
Status:
Recruiting
Contact:
Last name:
ZhengBo Song
Start date:
April 12, 2024
Completion date:
July 28, 2026
Lead sponsor:
Agency:
Bio-Thera Solutions
Agency class:
Industry
Source:
Bio-Thera Solutions
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06341114
