The Safety and Dosimetry Study of 177Lu-LNC1004 Injection

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

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 olderPatients 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 treatmentMeasurable disease as defined by Response Criteria in Solid Tumors (RECIST) version 1.1Overexpression 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 1Adequate organ function as defined by:Creatinine clearance ≥ 60 mL/min (calculated using the Cockcroft-Gault formula)Hemoglobin (Hb) > 9.0g/dLAbsolute neutrophil count (ANC) > 1.5 x 10^9/LPlatelets ≥100 x 109/LInternational normalized ratio (INR) < 1.5 for patients that are not on warfarinProthrombin time (PTT) < 2 x ULNTotal bilirubin < 1.5 x ULNSerum albumin > 2.8 g/dLAlanine aminotransferase (ALT) <3 x ULN, or <5 x ULN if deemed related to liver metastases from solid tumorAspartate aminotransferase (AST) <3 x ULN, or <5 x ULN if deemed related to liver metastases from solid tumorAll other toxicity parameters must be NCI-CTCAE v.5.0 Grade 0 or 1Women 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 breastfeedingHistory of allergic reactions attributed to compounds of similar chemical or biologic composition to 177Lu-LNC1004 as assessed from medical recordsParticipant has had prior chemotherapy or radical radiotherapy within 4 weeks before the first administration of study drugParticipant 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 treatmentParticipant 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 tumorClinically 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 0Active 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 illnessKnown brain metastases and/or carcinomatous meningitis, unless these metastases have been treated and stabilizedUncontrolled 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 requirementsPrior external beam radiation therapy involving >25% of the bone marrowUnmanageable urinary incontinence rendering the administration of 177Lu-LNC1004 unsafeOther 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 recurrenceUnable to comply with relevant contact precautions post 177Lu-LNC1004 treatmentAny other condition that may increase the risk associated with study participation or interfere with its interpretation.