This substudy presents the exploratory pharmacokinetic (PK) and dosimetry profile of XTR008, 177Lu-DOTATATE developed in China, from the phase 3 trial XT-XTR008-3-01. 10 patients with well-differentiated, locally advanced, or metastatic gastroenteropancreatic neuroendocrine tumors (GEP-NETs) received 4 cycles of 177Lu-DOTATATE (7.4 GBq/cycle). Postfirst dose, whole-body planar scintigraphy (up to 7 days), abdominal SPECT/CT (24/48 h), and blood and urine sampling for PK, safety, and efficacy assessment were performed. 177Lu-DOTATATE peaked in blood at 15 min, then decreased with a T1/2 of 37.36 ± 16.44 h. 60.38% was excreted in urine within 16 h. For four cycles, the mean absorbed doses to kidneys and red marrow were 18.914 ± 6.242 Gy (excluding one patient with nephrolithiasis and absorbed dose to kidneys of 77.1Gy) and 1.199 ± 0.337 Gy, respectively. Two patients had absorbed doses to the kidneys higher than 23 Gy (25.9 Gy, 23.1 Gy) without renal toxicity. Hematological toxicities (mostly grade 1/2) were the most common treatment-related adverse events (TRAEs). No significant association was found between organ doses and specific toxicities. Tumor absorbed dose varied widely (0.312–9.78 Gy/GBq). An objective response rate (ORR) was 30% (3/10); tumor dose did not significantly differ between responders (2.68 ± 2.53 Gy/GBq) and nonresponders (2.93 ± 1.81 Gy/GBq, p = 0.44). Tumor dose correlated moderately but nonsignificantly with size change (r = 0.016, p > 0.05). PRRT with XTR008 showed favorable tolerability, PK, and dosimetry in patients with advanced GEP-NETs, supporting its use in Chinese patients with well-differentiated GEP-NETs as a new treatment option.
Ma et al. (Thu,) studied this question.