Metastatic Lung Carcinoma, Non-Small Cell Lung Cancer
Conditions
Keywords
non-small cell lung cancer, Fibroblast Activation Protein, Yttrium-90 FAPI, Targeted Radionuclide Therapy, Phase II Clinical Trial, 90Y-FAPI Radioligand Therapy
Brief summary
Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related mortality worldwide and accounts for approximately 80% of all lung cancer cases. Despite advances in chemotherapy, radiotherapy, and immunotherapy, the prognosis of patients with advanced-stage metastatic NSCLC remains poor, with limited therapeutic options after the development of treatment resistance. Fibroblast Activation Protein (FAP) is highly expressed in cancer-associated fibroblasts in a wide range of solid tumors and represents a promising target for tumor-specific theranostic approaches. Gallium-68-labeled FAPI (Ga-68 FAPI) PET/CT has recently demonstrated high sensitivity in imaging primary lung tumors and metastatic lesions. This Phase II study aims to evaluate the safety, feasibility, dosimetry, and therapeutic efficacy of Yttrium-90-labeled FAPI (Y-90 FAPI) radionuclide therapy in patients with chemotherapy-resistant metastatic NSCLC showing significant FAP expression on Ga-68 FAPI PET/CT imaging.
Detailed description
Lung cancer remains the most common cause of cancer-related death globally, and non-small cell lung cancer (NSCLC) constitutes approximately 80% of all lung cancer cases. Patients with advanced or metastatic NSCLC have a particularly poor prognosis, with a 5-year survival rate of less than 10%, even among those who initially respond to systemic therapies. In patients with widespread metastatic disease, the addition of immune checkpoint inhibitors to chemotherapy and external beam radiotherapy provides only a limited survival benefit. Fibroblast Activation Protein (FAP) is a cell surface protein expressed in up to 90% of cancer-associated fibroblasts and has emerged as a novel tumor-specific therapeutic target. Recent clinical studies have demonstrated that Ga-68 FAPI PET/CT is highly effective in visualizing primary NSCLC lesions as well as pleural, nodal, adrenal, and brain metastases. Yttrium-90 (Y-90) is a beta-emitting radionuclide with a physical half-life of approximately 64 hours and favorable radiation characteristics for radionuclide therapy. Based on the high tumor uptake observed on Ga-68 FAPI PET/CT imaging, Y-90 FAPI is expected to selectively target FAP-expressing tumor lesions while minimizing radiation exposure to healthy tissues. Although large-scale clinical trials investigating Y-90 FAPI therapy are currently lacking, limited case-based applications have been reported in other solid tumors, including breast cancer and osteosarcoma. This Phase II study aims to address this gap by systematically evaluating Y-90 FAPI therapy in patients with chemotherapy-resistant metastatic NSCLC. Eligible patients will undergo Ga-68 FAPI PET/CT imaging prior to treatment. Patients demonstrating significant FAP expression in primary and metastatic tumor lesions will be selected for Y-90 FAPI radionuclide therapy. The radiolabeling of Y-90 FAPI will be performed under appropriate quality control conditions, including assessment of radiochemical purity and stability, prior to clinical administration. Y-90 FAPI will be administered intravenously to selected patients. Patients will be followed with clinical assessments, laboratory tests, and radiological imaging. Post-therapy imaging and dosimetric evaluations will be performed using Single Photon Emission Computed Tomography/Computed Tomography (SPECT/CT) to assess organ and tumor radiation doses. Safety and tolerability will be monitored throughout the study, and adverse events will be recorded and graded according to the Common Terminology Criteria for Adverse Events (CTCAE), version 5.0. This study aims to establish a novel nuclear medicine-based theranostic treatment approach for patients with metastatic NSCLC who have exhausted standard therapeutic options and to evaluate the potential of Y-90 FAPI as a safe and effective targeted radionuclide therapy.
Interventions
DRUGYttrium-90-Labeled Fibroblast Activation Protein Inhibitor (Y-90 FAPI)
Yttrium-90-labeled Fibroblast Activation Protein inhibitor (Y-90 FAPI) administered intravenously as targeted radionuclide therapy in patients with chemotherapy-resistant metastatic non-small cell lung cancer demonstrating significant FAP expression on Ga-68 FAPI PET/CT imaging.
Sponsors
Prof. Dr. Cemil Tascıoglu Education and Research Hospital Organization
Health Institutes of Turkey
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
This is a prospective, single-arm, open-label Phase II clinical study designed to evaluate the safety, dosimetry, and therapeutic efficacy of Yttrium-90-labeled Fibroblast Activation Protein inhibitor (Y-90 FAPI) in patients with chemotherapy-resistant metastatic non-small cell lung cancer (NSCLC). Eligible patients demonstrating significant FAP expression on Ga-68 FAPI PET/CT imaging will receive intravenous Y-90 FAPI radionuclide therapy. Clinical, biochemical, radiological, and dosimetric assessments will be performed to evaluate treatment response and safety.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age ≥18 years * Histologically confirmed diagnosis of non-small cell lung cancer (NSCLC) * Metastatic disease * Prior staging with F-18 FDG PET/CT * Ga-68 FAPI PET/CT demonstrating increased tracer uptake in tumor lesions (SUVmax ≥10 in more than 50% of metastatic lesions) * Disease progression or resistance after all standard approved therapies as determined by a multidisciplinary tumor board * Eastern Cooperative Oncology Group (ECOG) performance status 0-2 * Adequate organ function: * Serum creatinine ≤150 μmol/L * Hemoglobin ≥8.0 g/dL * White blood cell count ≥2.0 × 10⁹/L * Platelet count ≥50 × 10⁹/L * Total bilirubin ≤3 × upper limit of normal * Serum albumin ≥2.0 g/dL * Ability to understand and willingness to sign written informed consent
Exclusion criteria
* Age \<18 years * Diagnosis of small cell lung cancer * History of another active malignancy * Pregnancy or breastfeeding * Severe uncontrolled medical illness that would interfere with study participation * Refusal or inability to provide written informed consent
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 1. Safety and Tolerability | From first dose of Y-90 FAPI up to 6 months | Safety and Tolerability Measure Description: Incidence and severity of treatment-related adverse events following Y-90 FAPI therapy, graded according to the Common Terminology Criteria for Adverse Events (CTCAE), version 5.0. |
| Objective Tumor Response | Baseline to 3 months after treatment | Proportion of patients achieving complete or partial metabolic response on FDG PET/CT according to PERCIST criteria. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Dosimetry | Within 7 days after Y-90 FAPI administration | Absorbed radiation dose to tumor lesions and critical organs calculated using post-therapy SPECT/CT imaging. |
| Disease Control Rate | Up to 6 months | Proportion of patients achieving complete response, partial response, or stable disease after Y-90 FAPI therapy. |
| Progression-Free Survival (PFS) | Up to 12 months | Time from Y-90 FAPI administration to documented disease progression or death from any cause. |
| Overall Survival (OS) | Up to 12 months | Time from Y-90 FAPI therapy to death from any cause. |
| Correlation of FAP Expression With Treatment Response | Baseline to 3 months | Relationship between baseline Ga-68 FAPI PET/CT uptake values and post-treatment response outcomes. |
Countries
Turkey (Türkiye)
Contacts
CONTACTMuge O. Tamam, Professor
CONTACTMerve N Acar Tayyar
Outcome results
None listed