Trial Title:
The Safety and Dosimetry Study of 177Lu-LNC1004 Injection
NCT ID:
NCT05723640
Condition:
Solid Tumor, Unspecified, Adult
Study type:
Interventional
Study phase:
Phase 1
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:
177Lu-LNC1004 Injection group 1 radionuclide therapy
Description:
The treatment regimen will consist of a single dose 30mCi intravenous administration of
177Lu-LNC1004 Injection per 6-week cycle, for a total of 2 cycles, the dose per cycle
will be fixed.
Arm group label:
177Lu-LNC1004 Injection group 1
Intervention type:
Drug
Intervention name:
177Lu-LNC1004 Injection group 2 radionuclide therapy
Description:
The treatment regimen will consist of a single dose 60mCi intravenous administration of
177Lu-LNC1004 Injection per 6-week cycle, for a total of 2 cycles, the dose per cycle
will be fixed.
Arm group label:
177Lu-LNC1004 Injection group 2
Intervention type:
Drug
Intervention name:
177Lu-LNC1004 Injection group 3 radionuclide therapy
Description:
The treatment regimen will consist of a single dose 80mCi intravenous administration of
177Lu-LNC1004 Injection per 6-week cycle, for a total of 2 cycles, the dose per cycle
will be fixed.
Arm group label:
177Lu-LNC1004 Injection group 3
Intervention type:
Drug
Intervention name:
177Lu-LNC1004 Injection group 4 radionuclide therapy
Description:
The treatment regimen will consist of a single dose 100mCi intravenous administration of
177Lu-LNC1004 Injection per 6-week cycle, for a total of 2 cycles, the dose per cycle
will be fixed.
Arm group label:
177Lu-LNC1004 Injection group 4
Summary:
This proposal is a phase I, open-label study of a 4-Dose Regimen of Escalating Doses of
177Lu-LNC1004 Injection in patients with recurrent or metastatic, fibroblast activation
protein-positive solid tumors.
In the clinical development, we aim to demonstrate the following:
- 177Lu-LNC1004 Injection is safe and tolerable at therapeutic dose.
- Determination of dose(s) to be used in the expansion phase. The treatment regimen
will consist of a single dose intravenous administration of 177Lu-LNC1004 Injection
per 6-week cycle, for a total of 2 cycles. The dose per cycle will be fixed for each
patient and will be escalated in 4 different dose levels
Detailed description:
This proposal is a phase I, open-label study of a 4-Dose Regimen of Escalating Doses of
177Lu-LNC1004 Injection in patients with recurrent or metastatic, fibroblast activation
protein-positive solid tumors. The treatment regimen will consist of a single dose
intravenous administration of 177Lu-LNC1004 Injection per 6-week cycle, for a total of 2
cycles. The dose per cycle will be fixed for each patient and will be escalated in 4
different dose levels, from 30 mCi to 100 mCi (1.11 - 3.7 GBq).
This classic 3+3 design includes 3 patients for the first dose level group. If no DLT
occurs, 3 patients will be enrolled at the next dose level. If a DLT occurs at a certain
dose level, 3 additional patients will be enrolled at the previous dose level. The
highest dose with no more than 1 DLT out of 6 patients will be defined as MTD. If there
is no MTD observed after the dose escalation up to 100 mCi, a comprehensive evaluation
should be made by investigator and sponsor to determine whether an escalation to a higher
dose can be conducted or not based on the known safety, radiation dose and efficacy
characteristics.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Patients must have the ability to understand and sign an approved informed consent
form (ICF).
- Patients must have the ability to understand and comply with all protocol
requirements.
- Aged 21 years or older
- Patients must have histological, pathological, and/or cytological confirmation of
advanced/metastatic solid tumor that is refractory to or has progressed following
prior treatment and based on the current guidelines, there is no recommended
treatment
- Measurable disease as defined by Response Criteria in Solid Tumors (RECIST) version
1.1
- Overexpression of fibroblast activation protein of the target lesions at
68Ga-FAPI-46 positron emission tomography (PET)/computed tomography (CT) with
positive uptake (higher than adjacent background).
- Eastern Cooperative Oncology Group (ECOG) performance status (ECOG PS) score of 0 or
1
- Adequate organ function as defined by:
1. Creatinine clearance ≥ 60 mL/min (calculated using the Cockcroft-Gault formula)
2. Hemoglobin (Hb) > 9.0g/dL
3. Absolute neutrophil count (ANC) > 1.5 x 10^9/L
4. Platelets ≥100 x 109/L
5. International normalized ratio (INR) < 1.5 for patients that are not on
warfarin
6. Prothrombin time (PTT) < 2 x ULN
7. Total bilirubin < 1.5 x ULN
8. Serum albumin > 2.8 g/dL
9. Alanine aminotransferase (ALT) <3 x ULN, or <5 x ULN if deemed related to liver
metastases from solid tumor
10. Aspartate aminotransferase (AST) <3 x ULN, or <5 x ULN if deemed related to
liver metastases from solid tumor
- All other toxicity parameters must be NCI-CTCAE v.5.0 Grade 0 or 1
- Women of childbearing potential (WOCBP) must have a negative pregnancy test at study
entry. Subjects not considered WOCBP are those without menses for ≥ 12 consecutive
months, and those who have undergone hysterectomy and/or bilateral
salpingo-oophorectomy. WOCBP must be willing to use acceptable methods of birth
control (i.e., a hormonal contraceptive, intra-uterine device, diaphragm with
spermicide, or condom with spermicide, or abstinence) for the duration of the study
and 6 months after the last dose of treatment.
- Male participants with partners of childbearing potential are required to use
barrier contraception in addition to having their partner use another method of
contraception during the study and for 6 months after the last dose of treatment.
Male participants will also be advised to abstain from sexual intercourse with
pregnant or lactating women, or to use condoms.
- Previous surgery no less than 4 weeks prior to study entry.
Exclusion Criteria:
- Women who are pregnant or breastfeeding
- History of allergic reactions attributed to compounds of similar chemical or
biologic composition to 177Lu-LNC1004 as assessed from medical records
- Participant has had prior chemotherapy or radical radiotherapy within 4 weeks before
the first administration of study drug
- Participant has had prior targeted cancer therapy, immunotherapy, or treatment with
an investigational anticancer agent ≤ 14 days prior to receiving study treatment (≤
28 days prior in case of checkpoint inhibitor or other antibody therapies) before
the first administration of study drug.
- Received prior radiopharmaceutical therapy or radioembolization, or prior extensive
external beam radiation therapy (EBRT) to bone marrow or any prior EBRT to kidney,
or received any EBRT within 2 weeks prior to administration of study treatment
- Participant has not fully recovered from major surgery or significant traumatic
injury prior the first dose of study drug or expects to have major surgery during
the study period or within 3 months after the last dose of study drug.
- Life expectancy < 6 months as assessed by the treating physician
- > 80% liver involvement by tumor
- > 25% bone marrow involvement by tumor
- Clinically significant abnormalities on electrocardiogram (ECG) at screening
including QTcF > 470 ms regardless of sex or subjects who cannot tolerate high
volume load.
- Toxicities from prior therapies that have not resolved to grade 1 or grade 0
- Active and clinically significant bacterial, fungal, or viral infection, including
hepatitis B (HBV), hepatitis C (HBC), know human immunodeficiency virus (HIV), or
acquired immunodeficiency syndrome (AIDS)-related illness
- Known brain metastases and/or carcinomatous meningitis, unless these metastases have
been treated and stabilized
- Uncontrolled diabetes mellitus as defined by a HbA1c >9%
- Uncontrolled, intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that would limit compliance
with study requirements
- Prior external beam radiation therapy involving >25% of the bone marrow
- Unmanageable urinary incontinence rendering the administration of 177Lu-LNC1004
unsafe
- Other known co-existing malignancies except non-melanoma skin cancer and carcinoma
in situ of the uterine cervix, unless definitively treated and with no evidence of
recurrence
- Unable to comply with relevant contact precautions post 177Lu-LNC1004 treatment
- Any other condition that may increase the risk associated with study participation
or interfere with its interpretation.
Gender:
All
Minimum age:
21 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
National University Cancer Institute, Singapore National University Hospital, Singapore.
Address:
City:
Singapore
Zip:
119077
Country:
Singapore
Status:
Recruiting
Contact:
Last name:
weipeng Yong, Dr.
Phone:
6908 2222
Email:
Wei_Peng_YONG@nuhs.edu.sg
Start date:
October 3, 2023
Completion date:
March 30, 2025
Lead sponsor:
Agency:
Yantai LNC Biotechnology Singapore PTE. LTD.
Agency class:
Industry
Source:
Yantai LNC Biotechnology Singapore PTE. LTD.
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05723640
