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‌Purpose‌ <p>This phase I, first-in-human study evaluated the safety, dosimetry, and preliminary efficacy of <sup>177</sup>Lu-FAPI-XT, a novel fibroblast activation protein (FAP)-targeted radioligand, in patients with advanced solid tumors refractory to standard therapies.</p> ‌Methods‌ <p>This open-label, non-randomized, dose-escalation, investigator-initiated trial had a “accelerated titration” and “3 + 3” design involved a 6-week <sup>177</sup>Lu-FAPI-XT treatment cycle in patients with advanced-stage solid tumors at 3.7GBq initially, with subsequent cohorts receiving an incremental 1.85GBq dose increase until dose limiting toxicity (DLT) was observed.</p> ‌Results‌ <p><sup>177</sup>Lu-FAPI-XT was well tolerated and no DLT or grade ≥ 3 treatment-related adverse events (TRAE) were observed. The whole-body effective dose was 0.039 ± 0.013&#xa0;Sv/GBq. The mean effective half-lives for the whole-body and tumor lesions were 52.13 ± 12.33&#xa0;h and 31.78 ± 15.03&#xa0;h, respectively. According to RECIST stable disease (SD) were observed in 5 (5/14, 35.7%) patients, with the highest benefit observed in fibroblastic sarcoma subtypes with SD presented in 4 (4/8, 50%) patients. The median progression-free survival (PFS) was 4.63&#xa0;m (95%CI: 1.25, NE). Metabolic reductions on PET/CT were observed in 2 sarcoma cases. (URL: <a href="https://hclinicaltrials.gov">hclinicaltrials.gov</a>. Trial registration: NCT06211647, NCT06197139. Registered 4 January 2024.)</p> ‌conclusion‌ <p><sup>177</sup>Lu-FAPI-XT demonstrated a favorable safety profile, with preliminary signs of tumor response observed. Complete/partial response deficiency in <sup>177</sup>Lu-FAPI-XT therapy necessitate optimized strategies for efficacy improvement.</p>

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Safety and efficacy of 177Lu-FAPI-XT radioligand therapy in patients with advanced sarcoma and other cancer entities: first-in-human, dose-escalation study

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年10月15日

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  • Honghong Liu,
  • Rui Guo,
  • Xiaojun Zhang,
  • Huijuan Ji,
  • Shuwei Sun,
  • Shasha Sun,
  • Jiayong Liu,
  • Zhi Yang,
  • Ruimin Wang

摘要

‌Purpose‌

This phase I, first-in-human study evaluated the safety, dosimetry, and preliminary efficacy of 177Lu-FAPI-XT, a novel fibroblast activation protein (FAP)-targeted radioligand, in patients with advanced solid tumors refractory to standard therapies.

‌Methods‌

This open-label, non-randomized, dose-escalation, investigator-initiated trial had a “accelerated titration” and “3 + 3” design involved a 6-week 177Lu-FAPI-XT treatment cycle in patients with advanced-stage solid tumors at 3.7GBq initially, with subsequent cohorts receiving an incremental 1.85GBq dose increase until dose limiting toxicity (DLT) was observed.

‌Results‌

177Lu-FAPI-XT was well tolerated and no DLT or grade ≥ 3 treatment-related adverse events (TRAE) were observed. The whole-body effective dose was 0.039 ± 0.013 Sv/GBq. The mean effective half-lives for the whole-body and tumor lesions were 52.13 ± 12.33 h and 31.78 ± 15.03 h, respectively. According to RECIST stable disease (SD) were observed in 5 (5/14, 35.7%) patients, with the highest benefit observed in fibroblastic sarcoma subtypes with SD presented in 4 (4/8, 50%) patients. The median progression-free survival (PFS) was 4.63 m (95%CI: 1.25, NE). Metabolic reductions on PET/CT were observed in 2 sarcoma cases. (URL: hclinicaltrials.gov. Trial registration: NCT06211647, NCT06197139. Registered 4 January 2024.)

‌conclusion‌

177Lu-FAPI-XT demonstrated a favorable safety profile, with preliminary signs of tumor response observed. Complete/partial response deficiency in 177Lu-FAPI-XT therapy necessitate optimized strategies for efficacy improvement.