Evaluating the safety of 177Lu-LNC1004 Injection for treating solid tumors

Phase I, Open-Label Study of the Safety and Dosimetry of a 4-Dose Regimen of Escalating Doses of 177Lu-LNC1004 Injection in Adult Patients With Advanced Fibroblast Activation Protein (FAP)-Positive Solid Tumors

This study is testing a new injection to see if it is safe for people with certain types of solid tumors that keep coming back or spreading.

Quick facts

• Phase: PHASE1
• Study type: Interventional
• Enrollment: 24 (estimated)
• Ages: 21 Years and up
• Sex: All
• Sponsor: Yantai LNC Biotechnology Singapore PTE. LTD. (industry)
• Drugs / interventions: chemotherapy, immunotherapy, radiation
• Locations: 1 site (Singapore)
• Trial ID: NCT05723640 on ClinicalTrials.gov

What this trial studies

This phase I, open-label study investigates the safety and tolerability of escalating doses of 177Lu-LNC1004 Injection in patients with recurrent or metastatic fibroblast activation protein-positive solid tumors. Participants will receive a single intravenous dose every six weeks for two cycles, with doses ranging from 30 mCi to 100 mCi. The study employs a classic 3+3 design to determine the maximum tolerated dose (MTD) based on dose-limiting toxicities (DLTs). The goal is to establish a safe dosage for future expansion phases of the treatment.

Who should consider this trial

Good fit: Ideal candidates are adults aged 21 and older with advanced or metastatic solid tumors that are refractory to prior treatments and exhibit overexpression of fibroblast activation protein.

Not a fit: Patients with solid tumors that do not express fibroblast activation protein or those who have not progressed after standard treatments may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with advanced solid tumors that currently have no recommended treatment.

How similar studies have performed: While this approach is novel in its specific application, similar studies using radionuclide therapies have shown promise in treating various cancers.

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.

Where this trial is running

Singapore

• National University Cancer Institute, Singapore National University Hospital, Singapore. — Singapore, Singapore (RECRUITING)

Study contacts

• Study coordinator: Wei Peng Yong, Dr.

Conditions: Solid Tumor, Unspecified, Adult