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)”

Mini Oral session

Speakers: Aman Chauhan (Deerfield Beach, United States of America)

Lecture Time: 08:53 - 08:58

Background

177Lu-Dotatate is an FDA-approved somatostatin receptor-targeted radiopharmaceutical shown to improve progression-free survival (PFS) in patients with metastatic well-differentiated neuroendocrine tumors (NETs). Benchmark NETTER-1 trial established a median PFS of 28.4 months and an objective response rate (ORR) of 14% for Lu-177 dotatate. Triapine, an oral ribonucleotide reductase inhibitor, is a potent radiation sensitizer. This phase 1 study evaluated the safety and efficacy of combining triapine with 177Lu-Dotatate in patients with progressive NETs.

Methods

ETCTN 10388 is a multi-center, investigator-initiated, NCI-sponsored phase 1 trial conducted at six academic institutions in the United States. Eligible patients had metastatic, well-differentiated GEP-NETs and had progressed on at least one prior line of therapy. The study included a dose-escalation phase (Part A, n=15) utilizing a Bayesian Optimal Interval (BOIN) design, followed by a dose-expansion phase (Part B, n=16). All patients received 177Lu-Dotatate 200 mCi on Day 1 of each 8-week cycle, along with oral triapine (50–200 mg) on Days 1–14, for a total of four cycles.

Results

Thirty-one patients received study treatment. The most common treatment-related adverse events were anemia (94%), lymphopenia (88%), and thrombocytopenia (81%), which were largely transient and resolved within two weeks without impacting treatment continuity. Dose-limiting toxicities (DLTs) were observed in nine patients. Based on integrated safety and pharmacokinetic data, the recommended phase 2 dose (RP2D) of triapine was established at 150 mg. Among 28 patients evaluable for efficacy, the confirmed ORR was 21.4%, and the median PFS was 38.03 months. In the RP2D cohort, median PFS has not yet been reached and may exceed 40 months.

Conclusions

Triapine in combination with 177Lu-Dotatate was well tolerated and demonstrated encouraging signs of clinical activity in GEPNET patients. Triapine (150 mg) is the RP2D. A randomized phase 2 trial (ETCTN 10558) comparing the combination to 177Lu-dotatate monotherapy is currently enrolling at 14 sites across the United States.

Clinical trial identification

NCT 04234568.

Legal entity responsible for the study

NCI CTEP.

Funding

National Cancer Institute (CTEP).

Disclosure

A. Chauhan: Financial Interests, Personal, Steering Committee Member: Crinetics; Financial Interests, Personal, Advisory Board: Novartis, Curium, Sanofi; Financial Interests, Institutional, Research Funding: Seneca Therapeutics, EMD Serono, Nano Pharmaceutics; Financial Interests, Personal, Advisory Role: Boehringer Ingelheim, ITM; Financial Interests, Personal, Invited Speaker: TerSera. All other authors have declared no conflicts of interest.

https://cslide.ctimeetingtech.com/esmo2025/attendee/confcal/show/session/152