Trial Title:
A Study of the ILB-3101 in Patients With Advanced Solid Tumors
NCT ID:
NCT06426680
Condition:
Advanced Solid Tumor
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:
Biological
Intervention name:
ILB-3101
Description:
There are eight escalating dose cohorts.
Arm group label:
ILB-3101
Summary:
ILB-3101 is a fully humanized IgG1 antibody-drug conjugate (ADC) which specifically binds
to B7-H3, a target wildly expressed on solid tumor cells. The objectives of this study
are to investigate the safety, tolerability, pharmacokinetics and anti-tumor activity of
ILB-3101 in Chinese advanced solid tumor patients.
Detailed description:
This is an open-label, multi-center, dose-escalation and expansion, first-in-human phase
1 study in Chinese adult participants with locally advanced or metastatic solid tumors.
This study will consist of two parts: A Part Ia dose escalation stage and a Part Ib dose
expansion stage.
The objectives of this study are to evaluate the safety, tolerability, PK and preliminary
anti-tumor activity, describe the dose-limiting toxicities (DLTs), and determine the
maximum tolerated dose (MTD) or maximum administered dose (MAD) of HS-20093.
Part I: Participants with advanced cancer are eligible for dose escalation study if they
have progressed on or intolerant to available standard therapies, or no standard or
available curative therapy exists. The dose escalation will include an initial
accelerated titration design followed by 3+3 design.
Part II: Enrollment into dose expansion will begin after identification of the MTD or MAD
in Phase I. The dose expansion study will be conducted in populations with the following
indications: ovarian cancer, small cell lung cancer, head and neck squamous cell
carcinoma, soft tissue sarcoma (including uterine sarcoma), triple negative breast
cancer, esophageal squamous cell carcinoma, prostate cancer, etc..
All patients will be carefully followed for adverse events during the study treatment and
for 28 days after the last dose of study drug. Subjects will be permitted to continue
therapy with assessments for progression if the product is well tolerated and sustained
clinical benefit exists.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Have signed informed consent forms voluntarily.
2. 18-80 years old.
3. Having an ECOG performance status score of 0 or 1.
4. With an expected survival of more than 12 weeks.
5. Diagnosed histologically or cytologically with local advanced or metastatic solid
cancer, and under one of following situations: standard treatment-refractory
(disease progression or no response), treatment-resistant, unable to receive
treatment, or the standard treatment is unavailable.
6. Need to provide archived tumor tissue samples (Formalin fixed or paraffin embedded
tissue blocks or at least 5 unstained sections); During the dose escalation stage,
for subjects who are unable to provide tumor samples or have insufficient samples,
the decision to enroll may be made based on specific circumstances after discussion
with the sponsor.
7. At least one assessable tumor lesion is present during the dose escalation phase,
and according to RECIST version 1.1, at least one measurable tumor lesion is present
during the dose escalation phase (CRPC can be determined based on PCWG3).
8. Having sufficient bone marrow, liver, and kidney functions (based on the normal
value of the clinical trial site):
1. Absolute neutrophil count (ANC) ≥ 1.5×109/L.
2. Platelets ≥ 75×109/L.
3. Hemoglobin ≥ 90g/L.
4. Total serum bilirubin ≤ 1.5×upper limit of normal (ULN).
5. Without liver metastases, ALT, AST ≤ 2.5×ULN; with liver metastases, ALT, AST ≤
5×ULN.
6. Serum creatinine ≤1.5 × ULN.
7. Creatinine clearance rate (CrCl) (creatinine only ˃ Calculation required for
1.5 × ULN ≥50 mL/min (Calculate according to Cockcroft Fault formula),
8. International Normalized Ratio (INR) ≤ 1.5×ULN, APTT ≤ 1.5×ULN.
9. Echocardiographic LVEF (left ventricular ejection fraction) ≥ 50%.
10. QT interval corrected by Fridericia method (QTcF) Male<450ms; Female<470ms.
9. The serum pregnancy test results of female subjects of childbearing age are
negative.
10. Male or female patients of childbearing potential must agree to use effective
methods of contraception (such as double-barrier contraceptive methods, condoms,
oral or injectable contraceptives and intrauterine devices) during the study period
and within 90 days after the last dosing.
Exclusion Criteria:
1. Within 3 weeks prior to the first administration, systemic anti-tumor therapy has
been received, including chemotherapy, curative radiotherapy (palliative
radiotherapy for a single lesion within 3 weeks prior to enrollment is allowed, and
radiotherapy is not allowed for measurable lesions before enrollment unless it is
confirmed that the lesion has progressed after radiotherapy), biological therapy,
immunotherapy, etc., except for the following:
1. Received urea nitrite or mitomycin C within 6 weeks prior to the first use of
the study drug.
2. Oral administration of fluorouracil or small molecule targeted drugs within 2
weeks prior to the first use of the investigational drug or within 5 half-lives
of the drug (whichever is longer).
3. Individuals who have received endocrine therapy within 2 weeks prior to the
first use of the investigational drug.
4. Traditional Chinese patent medicines and simple preparations or traditional
Chinese medicine with anti-tumor indication within 1 week before the first use
of the study drug.
2. Patients who received other clinical trial drug within 4 weeks before the first
dosing.
3. Within 3 years prior to the first trial drug treatment, the patient had other active
malignant tumors, except for the tumors participating in this study and other
locally cured tumors (such as basal skin cancer, papillary thyroid cancer, or any
type of in situ cancer that has been completely removed, such as cervical in situ
cancer, ductal carcinoma in situ, etc.).
4. The presence of clinically uncontrollable pleural/abdominal effusion, pericardial
effusion, determined by the investigators as unsuitable for inclusion.
5. Suffering from central nervous system metastasis and/or cancerous meningitis. Except
for asymptomatic or asymptomatic central nervous system metastases that have been
clinically controlled but are judged stable by investigators, the following
conditions must also be met:
1. Stable clinical symptoms for at least 4 weeks before receiving trial drug
treatment.
2. No evidence of central nervous system disease progression was found in imaging
examinations within 4 weeks prior to the first trial drug treatment.
3. Antiepileptic drugs have been discontinued at least 2 weeks prior to the first
trial drug treatment, and the dosage of prednisone is ≤ 10mg/day or equivalent
dose of steroids.
4. For patients with intracranial lesions, if they have received treatment (such
as radiotherapy) before the first trial drug treatment, elution should be ≥ 2
weeks. Cancer induced encephalitis should be excluded regardless of its stable
clinical condition.
6. Receiving drug therapy known to prolong the QT interval or potentially lead to
torsade de pointe ventricular tachycardia; Or continue to receive these medications
during the research period.
7. Acute coronary syndrome occurring within the past 6 months, including myocardial
infarction, unstable angina, symptomatic congestive heart failure (New York Heart
Association classification II-IV), aortic dissection, stroke, or other grade 3 or
higher cardiovascular and cerebrovascular events; Serious cardiac rhythm or
conduction abnormalities, such as ventricular arrhythmias requiring clinical
intervention, II-III-degree atrioventricular block, etc.
8. Suffering from clinically uncontrollable diseases, including but not limited to
severe diabetes (diabetes ketoacidosis or hyperglycemia hyperosmolality occurred
within 6 months before the first administration, and the detection value of
glycosylated hemoglobin in the screening period was ≥ 7.5%); Refractory hypertension
(systolic blood pressure ≥ 150mmHg or diastolic blood pressure ≥ 100mmHg after
optimal medical treatment within the first month of screening) or a history of
hypertensive crisis or hypertensive encephalopathy.
9. Individuals with previous or current interstitial lung disease (excluding radiation
pneumonia that does not require hormone therapy).
10. Evidence of persistent uncontrolled systemic bacterial, fungal, or viral infections
(including HIV infection, HIV antibody positive; syphilis infected individuals) and
current need for intravenous anti infection treatment.
11. Provisions on hepatitis B and hepatitis C: if hepatitis B surface antigen (HBsAg) is
positive, and HBV-DNA>2000 IU/ml or 104 copies/ml, hepatitis B virus infected
persons should receive antiviral treatment according to local guidelines and
standards and are willing to receive antiviral treatment throughout the study
period; Hepatitis C antibody positive, and HCV RNA higher than the upper limit of
normal values in the study site;
12. Within 14 days prior to the first administration, systemic corticosteroids
(prednisone>10mg/day or equivalent doses of similar drugs) or other
immunosuppressive treatments have been received, except for the following:
1. Use local, ocular, intra-articular, intranasal, and inhaled corticosteroids for
treatment.
2. short term use of glucocorticoids for preventive treatment (such as preventing
contrast agent allergies).
13. Within 4 weeks before the first administration or planned to receive attenuated live
vaccines during the study period.
14. Having undergone major organ surgery (excluding biopsy) or significant trauma within
4 weeks prior to the first administration or requiring elective surgery during the
trial period.
15. Individuals who have received allogeneic hematopoietic stem cell transplantation or
organ transplantation in the past.
16. Known to have alcohol or drug dependence.
17. Individuals with mental disorders or poor compliance.
18. The adverse reactions of previous anti-tumor treatments have not yet recovered to
CTCAE5.0 ≤ Grade 1 (excluding toxicity judged by the investigators to have no safety
risk, such as hair loss, grade 2 peripheral neurotoxicity, stable hypothyroidism
after hormone replacement therapy, etc.);
19. Known to cause clinically significant allergic reactions to the active ingredients
and excipients, antibodies, and other monoclonal antibodies.
20. Pregnant (positive pregnancy test prior to dosing) or breast-feeding women.
21. The investigators believe that the subjects are not suitable to participate in this
clinical study due to other reasons.
Gender:
All
Minimum age:
18 Years
Maximum age:
80 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Fundan University Shanghai Cancer Center
Address:
City:
Shanghai
Country:
China
Status:
Recruiting
Contact:
Last name:
Zhang Jian, Doctor
Start date:
October 30, 2024
Completion date:
March 2026
Lead sponsor:
Agency:
Innolake Biopharm
Agency class:
Industry
Source:
Innolake Biopharm
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06426680
