Yittrium-90(Y-90) Fibroblast Activation Protein Inhibitor (FAPI) Therapy in Patients With Non-Small Cell Lung Cancer (Phase II)

NCT07500285 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: 49724
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 2

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.

Conditions

Non-Small Cell Lung Cancer; Metastatic Lung Carcinoma

Keywords

non-small cell lung cancer; Fibroblast Activation Protein; Yttrium-90 FAPI; Targeted Radionuclide Therapy; Phase II Clinical Trial; 90Y-FAPI Radioligand Therapy

Outcome Measures

Primary Outcomes (2)

• 1. Safety and Tolerability

  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.

  From first dose of Y-90 FAPI up to 6 months

• Objective Tumor Response

  Proportion of patients achieving complete or partial metabolic response on FDG PET/CT according to PERCIST criteria.

  Baseline to 3 months after treatment

Secondary Outcomes (5)

• Dosimetry

  Within 7 days after Y-90 FAPI administration

• Disease Control Rate

  Up to 6 months

• Progression-Free Survival (PFS)

  Up to 12 months

• Overall Survival (OS)

  Up to 12 months

• Correlation of FAP Expression With Treatment Response

  Baseline to 3 months

Study Arms (1)

Y-90 FAPI Radionuclide Therapy

EXPERIMENTAL

This single-arm study includes patients with histopathologically confirmed advanced non-small cell lung cancer (NSCLC) who are eligible for radioligand therapy. All enrolled participants will receive Yttrium-90-labeled FAPI (90Y-FAPI) administered intravenously according to the study protocol. Treatment will be performed under standardized radiation safety conditions. Patients will undergo baseline clinical and imaging evaluation prior to therapy and will be followed prospectively with clinical assessment, laboratory tests, and serial imaging (including FAPI PET/CT and/or conventional imaging) to evaluate treatment response, biodistribution, dosimetry, safety, and tolerability. Adverse events will be monitored and recorded throughout the study period in accordance with CTCAE criteria.

Drug: Yttrium-90-Labeled Fibroblast Activation Protein Inhibitor (Y-90 FAPI)

Interventions

Yttrium-90-Labeled Fibroblast Activation Protein Inhibitor (Y-90 FAPI) DRUG

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.

Also known as: Y-90-labeled FAPI, Y-90 FAPI Radioligand Therapy, FAP-Targeted Radionuclide Therapy

Y-90 FAPI Radionuclide Therapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Prof. Dr. Cemil Tascıoglu Education and Research Hospital Organization: lead
• Health Institutes of Turkey: collaborator

Study Sites (2)

Prof. Dr. Cemil Taşcıoğlu City Hospital

Istanbul, 34384, Turkey (Türkiye)

Location

Prof. Dr. Cemil Taşçıoğlu City Hospital

Istanbul, 34384, Turkey (Türkiye)

Location

Related Publications (3)

• Rathke H, Fuxius S, Giesel FL, Lindner T, Debus J, Haberkorn U, Kratochwil C.Two Tumors, One Target: Preliminary Experience With 90Y-FAPI Therapy in a Patient With Metastasized Breast and Colorectal Cancer. Clin Nucl Med. 2021 Oct 1;46(10):842-844. doi: 10.1097/RLU.0000000000003842.

  BACKGROUND

• Fendler WP, Pabst KM, Kessler L, Fragoso Costa P, Ferdinandus J, Weber M, Lippert M, Lueckerath K, Umutlu L, Kostbade K, Mavroeidi IA, Schuler M, Ahrens M, Rischpler C, Bauer S, Herrmann K, Siveke JT, Hamacher R.Safety and Efficacy of 90Y-FAPI-46 Radioligand Therapy in Patients with Advanced Sarcoma and Other Cancer Entities.Clin Cancer Res. 2022 Oct 3;28(19):4346-4353. doi: 10.1158/1078-0432.CCR-22-1432

  BACKGROUND

• Privé BM, Boussihmad MA, Timmermans B, van Gemert WA, Peters SMB, Derks YHW, van Lith SAM, Mehra N, Nagarajah J, Heskamp S, Westdorp H. Fibroblast activation protein-targeted radionuclide therapy: background, opportunities, and challenges of first (pre)clinical studies. Eur J Nucl Med Mol Imaging. 2023 Jun;50(7):1906-1918. doi: 10.1007/s00259-023-06144-0. Epub 2023 Feb 23.

  BACKGROUND

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Lung Neoplasms

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Central Study Contacts

Muge O. Tamam, Professor

CONTACT

+90532402376; mugetamam@yahoo.com

Merve N Acar Tayyar

CONTACT

+905532079693; nurmacar13@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor Doctor

Model Details: 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.

Study Record Dates

• First Submitted: February 28, 2026
• First Posted: March 30, 2026
• Study Start: April 10, 2026
• Primary Completion (Estimated): June 15, 2027
• Study Completion (Estimated): November 15, 2027
• Last Updated: March 31, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

TU (2)