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177Lu-LNC1004 Radioligand Therapy in Patients with End-stage Metastatic Cancers: A Single-Center, Single-Arm, Phase
Hao Fu1, Jingxiong Huang1, Liang Zhao1
1Department of Nuclear Medicine and Minnan PET Center, Xiamen Key Laboratory of Radiopharmaceuticals, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China.
Purpose:
Fibroblast activation protein (FAP) is highly expressed in cancer-associated fibroblasts and certain tumor cells, making it a promising therapeutic target for various malignancies. This study evaluated the efficacy and safety of 177Lu-Evans blue-FAP inhibitor (177Lu-LNC1004) radioligand therapy (RLT) for treating end-stage metastatic tumors.
Patients And Methods:
This single-arm, single-center, phase II trial included 28 patients with progressive metastatic malignancies (11 types) and high FAP expression (defined as a maximum standardized uptake value ≥10 in >50% of tumors) who had exhausted all approved therapies, screened between June 2022 and April 2024. Patients were scheduled to receive four 177Lu-LNC1004 RLT cycles at 3.33 GBq/cycle every 6 weeks. The primary endpoint was post-RLT radiologic response. The secondary endpoints were progression-free survival (PFS), overall survival (OS), dosimetry, and safety.
Results:
Eastern Cooperative Oncology Group scores >2 were observed in 68% of patients. Overall, 63 177Lu-LNC1004 RLT cycles were performed, with 19 (68%) patients undergoing ≥2 cycles. Disease control was achieved in 13 (13/28, 46%) patients, with 4 and 9 patients demonstrating partial response and stable disease, respectively, and associated with improved PFS and OS (P < 0.001). The mean absorbed dose in tumors was 4.69 ± 3.83 Gy/GBq (1.18-25.03 Gy/GBq). Treatment-related grade 3/4 hematotoxicity was observed in six (21%) patients, with thrombocytopenia, leukopenia, and neutropenia most prevalent. No grade 3/4 hepatotoxicity or nephrotoxicity was observed.
Conclusions:
FAP-directed RLT using 177Lu-LNC1004 at 3.33 GBq/cycle was well tolerated with an acceptable toxicity profile. Nearly half of patients achieved disease control, which was associated with prolonged PFS and OS.
Insights
Fibroblast activation protein (FAP)-targeted radioligand therapy (RLT) with 177Lu-LNC1004 showed promise in advanced cancers. Nearly half of patients achieved disease control, correlating with improved survival and an acceptable safety profile.
Area of Science:
- Oncology
- Nuclear Medicine
- Radiopharmaceutical Therapy
Background:
- Fibroblast activation protein (FAP) is a key target in cancer therapy due to its high expression in cancer-associated fibroblasts and tumor cells.
- Radioligand therapy (RLT) offers a targeted approach to deliver radiation directly to tumors expressing specific biomarkers.
Purpose of the Study:
- To evaluate the efficacy and safety of 177Lu-Evans blue-FAP inhibitor (177Lu-LNC1004) RLT in patients with end-stage metastatic tumors and high FAP expression.
- To assess radiologic response, progression-free survival (PFS), overall survival (OS), dosimetry, and safety of 177Lu-LNC1004 RLT.
Main Methods:
- A single-arm, single-center, phase II trial involving 28 patients with progressive metastatic malignancies and high FAP expression (SUVmax ≥10 in >50% of tumors).
- Patients received four cycles of 177Lu-LNC1004 RLT at 3.33 GBq/cycle every 6 weeks.
- Primary endpoint was post-RLT radiologic response; secondary endpoints included PFS, OS, dosimetry, and safety.
Main Results:
- Disease control was achieved in 46% of patients (4 partial response, 9 stable disease), associated with significantly improved PFS and OS (P < 0.001).
- The mean absorbed dose in tumors was 4.69 ± 3.83 Gy/GBq.
- Grade 3/4 hematotoxicity occurred in 21% of patients (thrombocytopenia, leukopenia, neutropenia); no grade 3/4 hepatotoxicity or nephrotoxicity was observed.
Conclusions:
- FAP-directed RLT using 177Lu-LNC1004 demonstrated an acceptable toxicity profile and was well tolerated.
- Nearly half of patients achieved disease control, indicating the potential of this therapy for advanced metastatic cancers.
- The observed disease control was linked to prolonged PFS and OS, supporting further investigation of 177Lu-LNC1004 RLT.
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