Background: Radiation is a potent inducer of DNA double-strand breaks, and ribonucleotide reductase (RNR) is the rate-limiting enzyme for conversion of ribonucleoside diphosphate to deoxyribonucleotide diphosphate, and thus repair of DNA in this setting. ETCTN 10388 evaluated safety of combination Lu-177 DOTATATE, a beta-emitting radionuclide in combination with triapine, a ribonucleotide reductase (RNR) inhibitor. Methods: This investigator initiated, NCI sponsored, multicenter phase 1 trial, enrolled a total of 31 patients in the dose escalation [using the Bayesian optimal interval design (BOIN)] and dose expansion cohorts. Oral triapine was administered on days 1-14 and Lu-177 DOTATATE [200 mCi] intravenously on day 1 of every 56-day cycle. A total of 4 cycles were administered. All enrolled patients had blood samples collected for triapine pharmacokinetic (PK) analysis in EDTA tubes prior to and at 0.5, 1, 1.5, 2, 3, 4, 6, and 8 h after oral administration during cycle 1. Results: Five patients were enrolled in triapine Dose Level 1 (100 mg/day), twenty-five to dose level two (150 mg/day), and one patient to dose level three (200 mg/day). PK data were available for 12 patients enrolled in the dose escalation cohort. The geometric mean (SD) AUC_0-inf was 1159 (1.22) µg/L•h for the 100mg dose level and 1862 (1.76) µg/L•h for the 150 mg dose level, suggesting that exposure increased with dose, and inter-patient variability was as expected for an oral agent. Triapine PK parameter values observed in this trial, were comparable to previous reports that used a previous formulation [1]. While exposure was similar, variability appeared smaller with the current oral formulation. Adverse events (AE) were assessed in all 31 patients per CTCAE 5.0. A total of one DLT in dose level 1, seven DLTs (Transient cytopenia; primarily neutropenia and rarely thrombocytopenia) in dose level 2, and one grade 5 DLT (Death probably from progressive cancer and carcinoid heart disease but possibly from trial drugs) in dose level 3 were observed. Detailed AE profile will be presented at the meeting. Conclusions: The RP2D of triapine is 150 mg QD on days 1-14 in combination with Lu-177 DOTATATE on day 1 of every 56-day cycle. Clinical trial information: 04234568.