Clinical Trial · NCT05723640

The Safety and Dosimetry Study of 177Lu-LNC1004 Injection

Overview

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

Sponsor

Yantai LNC Biotechnology Singapore PTE LTD

Phase

Phase 1

ClinicalTrials.gov

NCT05723640

Drug / Compound

LNC1004

Isotope(s):

Target(s):

Ligand Class: Small Molecules

Chelator: DOTA

Eligibility

Inclusion

Adequate organ function as defined by:
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.
Aspartate aminotransferase (AST) \<3 x ULN, or \<5 x ULN if deemed related to liver metastases from solid tumor
Total bilirubin \< 1.5 x ULN
All other toxicity parameters must be NCI-CTCAE v.5.0 Grade 0 or 1
Creatinine clearance ≥ 60 mL/min (calculated using the Cockcroft-Gault formula)
Alanine aminotransferase (ALT) \<3 x ULN, or \<5 x ULN if deemed related to liver metastases from solid tumor
Platelets ≥100 x 109/L
Previous surgery no less than 4 weeks prior to study entry.
Eastern Cooperative Oncology Group (ECOG) performance status (ECOG PS) score of 0 or 1
Patients must have the ability to understand and comply with all protocol requirements.
Absolute neutrophil count (ANC) \> 1.5 x 10\^9/L
International normalized ratio (INR) \< 1.5 for patients that are not on warfarin
Serum albumin \> 2.8 g/dL
Hemoglobin (Hb) \> 9.0g/dL
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).
Prothrombin time (PTT) \< 2 x ULN
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.
Measurable disease as defined by Response Criteria in Solid Tumors (RECIST) version 1.1
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

Exclusion

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.
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.
Clinically significant abnormalities on electrocardiogram (ECG) at screening including QTcF \> 470 ms regardless of sex or subjects who cannot tolerate high volume load.
Life expectancy \< 6 months as assessed by the treating physician
Prior external beam radiation therapy involving \>25% of the bone marrow
History of allergic reactions attributed to compounds of similar chemical or biologic composition to 177Lu-LNC1004 as assessed from medical records
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
Women who are pregnant or breastfeeding
Participant has had prior chemotherapy or radical radiotherapy within 4 weeks 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
\> 25% bone marrow involvement by tumor
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.
Unmanageable urinary incontinence rendering the administration of 177Lu-LNC1004 unsafe
Toxicities from prior therapies that have not resolved to grade 1 or grade 0
Uncontrolled diabetes mellitus as defined by a HbA1c \>9%
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