Multi-center Phase 1 study of Triapine in Combination with [177Lu]Lutetium-Dotatate in Patients with Well-Differentiated Neuroendocrine Tumors (ETCTN 10388)

INTRODUCTION: Next generation of Theranostics studies are looking at novel combinations with radiation sensitizers to enhance PRRT's efficacy. Here, we present safety and efficacy data from a multi-center phase 1 study of a [¹⁷⁷Lu]lutetium-dotatate -triapine combination in patients with GEP-NETs. METHODS: The study consisted of two phases (dose escalation and expansion) administering the recommended phase 2 doses (RP2D) for the two agents. All patients received 200 mCi of [¹⁷⁷Lu]lutetium-dotatate on day 1 of four 8-week cycles, in combination with oral triapine administered at assigned dose levels (100 mg, 150 mg or 200mg) from days 1 to 14 of each cycle. RESULTS: A total of 31 (A: 15 ; B: 16 ) patients received treatment. Nine patients experienced dose-limiting toxicities; Grade 3 anemia (n=1), Grade 5 cardiac arrest (n=1), and Grade 4 neutropenia (n=7). Based on the overall safety and pharmacokinetics data, a [¹⁷⁷Lu]lutetium-dotatate (200 mCi) plus triapine (150 mg) dose was selected as the RP2D for the expansion phase. Grade ≥3 treatment related adverse events were observed in 77% patients: anemia (23%), nausea and vomiting (3% ), lymphopenia ( 58%), neutropenia ( 35%) and leukopenia ( 39%). The majority of cytopenias were transient and resolved within two weeks. Among the 28 evaluable patients, the objective response rate (ORR) was 21.4% and the median progression-free survival (mPFS) has not been reached (median follow-up period: 23.7 months). CONCLUSIONS: The combination of [¹⁷⁷Lu]lutetium-dotatate (200 mCi) and oral triapine (150 mg D1-14) was well tolerated and demonstrated preliminary activity in patients with well-differentiated GEP-NETs. (NCT04234568).

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Journal
Clinical Cancer Research
Published
2026-07-28
DOI
https://doi.org/10.1158/1078-0432.ccr-26-0686
Primary Topic
Neuroendocrine Tumor Research Advances
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article
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article

Multi-center Phase 1 study of Triapine in Combination with [177Lu]Lutetium-Dotatate in Patients with Well-Differentiated Neuroendocrine Tumors (ETCTN 10388)

Lowell Anthony, Elise C. Kohn, Donglin Yan, Peter I-Fan Wu et al.
Clinical Cancer Research
Neuroendocrine Tumor Research Advances
article

Multi-center Phase 1 study of Triapine in Combination with [177Lu]Lutetium-Dotatate in Patients with Well-Differentiated Neuroendocrine Tumors (ETCTN 10388)

Lowell Anthony, Elise C. Kohn, Donglin Yan, Peter I-Fan Wu, Heidi L. Weiss, Jan H. Beumer, Susanne M. Arnold, Larry Rubinstein, Susan M. Christner, Bhavana Konda, Mary F. Mulcahy, Daneng Li, Aman Khurana, Heloisa P. Soares, Heather A. Jacene, William Edgar Carson, S. Percy Ivy, Þorvarður R. Hálfdánarson, Rakhi Modak, Biswajit Das, Steven D. Gore, Aman Chauhan, Charles Kunos, Rani Jayswal
article en

Abstract

INTRODUCTION: Next generation of Theranostics studies are looking at novel combinations with radiation sensitizers to enhance PRRT's efficacy. Here, we present safety and efficacy data from a multi-center phase 1 study of a [¹⁷⁷Lu]lutetium-dotatate -triapine combination in patients with GEP-NETs. METHODS: The study consisted of two phases (dose escalation and expansion) administering the recommended phase 2 doses (RP2D) for the two agents. All patients received 200 mCi of [¹⁷⁷Lu]lutetium-dotatate on day 1 of four 8-week cycles, in combination with oral triapine administered at assigned dose levels (100 mg, 150 mg or 200mg) from days 1 to 14 of each cycle. RESULTS: A total of 31 (A: 15 ; B: 16 ) patients received treatment. Nine patients experienced dose-limiting toxicities; Grade 3 anemia (n=1), Grade 5 cardiac arrest (n=1), and Grade 4 neutropenia (n=7). Based on the overall safety and pharmacokinetics data, a [¹⁷⁷Lu]lutetium-dotatate (200 mCi) plus triapine (150 mg) dose was selected as the RP2D for the expansion phase. Grade ≥3 treatment related adverse events were observed in 77% patients: anemia (23%), nausea and vomiting (3% ), lymphopenia ( 58%), neutropenia ( 35%) and leukopenia ( 39%). The majority of cytopenias were transient and resolved within two weeks. Among the 28 evaluable patients, the objective response rate (ORR) was 21.4% and the median progression-free survival (mPFS) has not been reached (median follow-up period: 23.7 months). CONCLUSIONS: The combination of [¹⁷⁷Lu]lutetium-dotatate (200 mCi) and oral triapine (150 mg D1-14) was well tolerated and demonstrated preliminary activity in patients with well-differentiated GEP-NETs. (NCT04234568).

Clinical Cancer Research
Northwestern University (US), University of Kentucky HealthCare (US), National Institutes of Health (US), City Of Hope National Medical Center (US), Beth Israel Deaconess Medical Center (US), Mayo Clinic (US), University of Kentucky (US), Lexmark (United States) (US), University of California, San Francisco (US), University of Utah (US), Markey Cancer Center (US), Northwestern University (PH), Dana-Farber Cancer Institute (US), Mayo Clinic in Arizona (US), UPMC Hillman Cancer Center (US), Frederick National Laboratory for Cancer Research (US), National Cancer Institute (MY), National Cancer Institute (US), Mayo Clinic in Florida (US), Sylvester Comprehensive Cancer Center (US), Sidney Kimmel Comprehensive Cancer Center (US), The Ohio State University (US), University of San Francisco (US)
Good health and well-being
Openalex Percentile: Top 8%
Neuroendocrine Tumor Research Advances
DOISourceOpenAlex
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