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ESMO Abstract “1709MO - Multi-center NCI-sponsored phase I study of triapine in combination with 177Lu-dotatate in patients with well-differentiated gastroenteropancreatic neuroendocrine tumours (GEP-NETs)”
ESMO Abstract “1709MO - Multi-center NCI-sponsored phase I study of triapine in combination with 177Lu-dotatate in patients with well-differentiated gastroenteropancreatic neuroendocrine tumours (GEP-NETs)”.
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[{"type":"text","content":"Mini Oral session\r\nSpeakers: Aman Chauhan (Deerfield Beach, United States\r\nof America)\r\nLecture Time: 08:53 - 08:58\r\nBackground\r\n177Lu-Dotatate is an FDA-approved somatostatin\r\nreceptor-targeted radiopharmaceutical shown to improve progression-free\r\nsurvival (PFS) in patients with metastatic well-differentiated neuroendocrine\r\ntumors (NETs). Benchmark NETTER-1 trial established a median PFS of 28.4 months\r\nand an objective response rate (ORR) of 14% for Lu-177 dotatate. Triapine, an\r\noral ribonucleotide reductase inhibitor, is a potent radiation sensitizer. This\r\nphase 1 study evaluated the safety and efficacy of combining triapine with 177Lu-Dotatate\r\nin patients with progressive NETs.\r\nMethods\r\nETCTN 10388 is a multi-center, investigator-initiated,\r\nNCI-sponsored phase 1 trial conducted at six academic institutions in the\r\nUnited States. Eligible patients had metastatic, well-differentiated GEP-NETs\r\nand had progressed on at least one prior line of therapy. The study included a\r\ndose-escalation phase (Part A, n=15) utilizing a Bayesian Optimal Interval\r\n(BOIN) design, followed by a dose-expansion phase (Part B, n=16). All patients\r\nreceived 177Lu-Dotatate 200 mCi on Day 1 of each 8-week cycle, along with oral\r\ntriapine (50–200 mg) on Days 1–14, for a total of four cycles.\r\nResults\r\nThirty-one patients received study treatment. The most\r\ncommon treatment-related adverse events were anemia (94%), lymphopenia (88%),\r\nand thrombocytopenia (81%), which were largely transient and resolved within\r\ntwo weeks without impacting treatment continuity. Dose-limiting toxicities\r\n(DLTs) were observed in nine patients. Based on integrated safety and\r\npharmacokinetic data, the recommended phase 2 dose (RP2D) of triapine was\r\nestablished at 150 mg. Among 28 patients evaluable for efficacy, the confirmed ORR\r\nwas 21.4%, and the median PFS was 38.03 months. In the RP2D cohort, median PFS\r\nhas not yet been reached and may exceed 40 months.\r\nConclusions\r\nTriapine in combination with 177Lu-Dotatate was well\r\ntolerated and demonstrated encouraging signs of clinical activity in GEPNET\r\npatients. Triapine (150 mg) is the RP2D. A randomized phase 2 trial (ETCTN\r\n10558) comparing the combination to 177Lu-dotatate monotherapy is currently\r\nenrolling at 14 sites across the Unite...