The Safety and Dosimetry Study of 177Lu-LNC1004 Injection

Inclusion Criteria:

• Patients must have the ability to understand and sign an approved informed consentform (ICF).
• Patients must have the ability to understand and comply with all protocolrequirements.
• Aged 21 years or older
• Patients must have histological, pathological, and/or cytological confirmation ofadvanced/metastatic solid tumor that is refractory to or has progressed followingprior 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-46positron 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 livermetastases from solid tumor
10. Aspartate aminotransferase (AST) <3 x ULN, or <5 x ULN if deemed related to livermetastases 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 studyentry. Subjects not considered WOCBP are those without menses for ≥ 12 consecutivemonths, and those who have undergone hysterectomy and/or bilateralsalpingo-oophorectomy. WOCBP must be willing to use acceptable methods of birthcontrol (i.e., a hormonal contraceptive, intra-uterine device, diaphragm withspermicide, or condom with spermicide, or abstinence) for the duration of the studyand 6 months after the last dose of treatment.
• Male participants with partners of childbearing potential are required to use barriercontraception in addition to having their partner use another method of contraceptionduring the study and for 6 months after the last dose of treatment. Male participantswill also be advised to abstain from sexual intercourse with pregnant or lactatingwomen, 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 biologiccomposition to 177Lu-LNC1004 as assessed from medical records
• Participant has had prior chemotherapy or radical radiotherapy within 4 weeks beforethe first administration of study drug
• Participant has had prior targeted cancer therapy, immunotherapy, or treatment with aninvestigational anticancer agent ≤ 14 days prior to receiving study treatment (≤ 28days prior in case of checkpoint inhibitor or other antibody therapies) before thefirst administration of study drug.
• Received prior radiopharmaceutical therapy or radioembolization, or prior extensiveexternal beam radiation therapy (EBRT) to bone marrow or any prior EBRT to kidney, orreceived any EBRT within 2 weeks prior to administration of study treatment
• Participant has not fully recovered from major surgery or significant traumatic injuryprior the first dose of study drug or expects to have major surgery during the studyperiod 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 includingQTcF > 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, includinghepatitis B (HBV), hepatitis C (HBC), know human immunodeficiency virus (HIV), oracquired immunodeficiency syndrome (AIDS)-related illness
• Known brain metastases and/or carcinomatous meningitis, unless these metastases havebeen treated and stabilized
• Uncontrolled diabetes mellitus as defined by a HbA1c >9%
• Uncontrolled, intercurrent illness including, but not limited to, ongoing or activeinfection, symptomatic congestive heart failure, unstable angina pectoris, cardiacarrhythmia, or psychiatric illness/social situations that would limit compliance withstudy 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 insitu of the uterine cervix, unless definitively treated and with no evidence ofrecurrence
• Unable to comply with relevant contact precautions post 177Lu-LNC1004 treatment
• Any other condition that may increase the risk associated with study participation orinterfere with its interpretation.