Multicenter phase 1 study of triapine plus [¹⁷⁷Lu]lutetium-dotatate for well-differentiated GEP-NETS

A multicenter phase 1 trial in the United States evaluated the combination of triapine plus [¹⁷⁷Lu]lutetium-dotatate in patients with well-differentiated gastroenteropancreatic neuroendocrine tumors (GEP-NETs). In the dose escalation part, 15 patients received 200 mCi of [¹⁷⁷Lu]lutetium-dotatate on day 1 of four 8-week cycles, in combination with oral triapine (100, 150, or 200 mg) on days 1 to 14 or each cycle. Based on the overall safety and pharmacokinetics results, triapine 150 mg was selected as the phase 2 recommended dose for the expansion phase, including 16 patients. Nine patients experienced dose-limiting toxicities: grade 5 cardiac arrest (n=1), grade 4 neutropenia (n=7), and grade 3 anemia (n=1). Grade ≥ 3 treatment-related adverse events were observed in 77% of the patients, lymphopenia and leukopenia being the most common. The majority of cytopenias were transient and resolved within two weeks. Among the 28 evaluable patients, the objective response rate was 21.4% and the median progression-free survival was not reached during a median of 23.7 months of follow-up. The authors conclude that the combination of [¹⁷⁷Lu]lutetium-dotatate and triapine was well tolerated and demonstrated preliminary activity in patients with well-differentiated GEP-NETs.