XTR008 Demonstrates Survival and Response Superiority in SSTR+ GEP-NETs

XTR008, a no-carrier-added ¹⁷⁷Lu-dotatate-based peptide receptor radionuclide therapy (PRRT), significantly improved progression-free survival (PFS), overall response rate (ORR), and quality of life with a manageable safety profile compared with high-dose octreotide long-acting repeatable (LAR) in patients with well-differentiated, somatostatin receptor (SSTR)-positive gastroenteropancreatic neuroendocrine tumors (GEP-NETs).¹

The data from the phase 3 XT-XTR008-3-01 study (NCT05459844) were presented at the 2025 European Society for Medical Oncology (ESMO) Congress by Rongrui Liu, MD, associate chief physician at Chinese PLA Hospital in Beijing, China. As of an interim analysis in June 2024, the median PFS was not reached (NR; 95% CI, 16.13–not evaluable [NE]) with XTR008 vs 5.78 months (95% CI, 5.65–8.41) with octreotide LAR (HR, 0.06; 95% CI, 0.031–0.135; P <.0001). At a subsequent analysis in June 2025, the PFS benefit was maintained with XTR008 with a median of 24.77 months (95% CI, 22.11–NE).

While overall survival (OS) data were not mature, a positive trend was observed in the XTR008 arm with a separation of Kaplan-Meier curves beginning around 9 months after randomization.

ORR in the XTR008 arm was 55.6% as of the data cutoff of June 2025, with a median duration of response (DOR) of 19.8 months (95% CI, 11.04–NE). Further, 39.3% of patients achieved stable disease. In the octreotide LAR arm, the ORR was 2.1%, the median DOR was 8.4 months (95% CI, NE–NE), and 70.1% of patients achieved stable disease.

XTR008 also improved quality of life compared with octreotide LAR across multiple dimensions, including functional and symptom scales.

What Were the Safety Findings?

Regarding safety, the most common treatment-related adverse events (TRAEs) were hematologic toxicities including decreased lymphocytes (72.4%), anemia (54.1%), neutropenia (49.0%), and decreased platelets (49.0%). A total of 95.9% (n = 94) of patients in the XTR008 arm and 58.3% (n = 56) of patients in the octreotide LAR arm experienced TRAEs, with grade ≥3 TRAEs occurring in a respective 51.0% (n = 50) and 11.5% (n = 11) of patients.

What Was the Study Design?

The XT-XTR008-3-01 study randomized patients across sites in China 1:1 to receive XTR008 (n = 99) at 200 mCi every 8 weeks for 4 cycles or octreotide LAR (n = 97) 60 mg every 4 weeks. The primary end point was PFS, and secondary end points included DOR, OS, quality of life, and disease control rate.

Patients were required to have confirmed low/intermediate-grade (G1/G2) advanced GEP-NET, disease progression after at least 12 weeks of fixed dose octreotide LAR, and an ECOG performance status of 0 to 1.

Stratification factors included primary tumor site (pancreatic vs nonpancreatic), pathological tumor grade (1 vs 2), and duration of most recent treatment (≤6 months vs >6 months).

What Was the Rationale for the Trial?

GEP-NETs exhibit considerable heterogeneity, making it challenging to develop effective treatments. Further, in later-line settings, the tumors become more aggressive and resistant. In China, the distribution of GEP-NETs originates more from primary pancreatic, gastric, and rectal sites; comparatively, in Western populations, midgut origins are most common.

While the phase 3 NETTER-1 trial (NCT01578239) established PRRT as a standard treatment for midgut NETs, the evidence remains limited for its efficacy in NETs from other primary sites.

DISCLOSURES: Dr Liu declared no conflict of interest.

REFERENCE:

Liu R, XT-XTR008-3-01: phase III study of 177Lu-Dotatate versus high-dose octreotide long-acting repeatable (LAR) in patients with advanced grade 1–2, well-differentiated, gastroenteropancreatic neuroendocrine tumours (GEP-NETs). Presented at: 2025 ESMO Congress; October 17–20, 2025; Berlin, Germany. Abstract LBA63.