Background Ixazomib is an oral proteasome inhibitor under phase 3 investigation in pts with multiple myeloma and AL amyloidosis. Ixazomib citrate, a prodrug, rapidly hydrolyzes to the active moiety, ixazomib, in plasma. Metabolism appears to be the major route of elimination for ixazomib. This phase 1, open-label, multicenter, parallel-group study (NCT01454076) investigated the effect of rifampin, an established strong CYP3A inducer, on the pharmacokinetics (PK) of ixazomib. Methods Adult pts with advanced solid tumors (Eastern Cooperative Oncology Group Performance Status 0 or 1), for which no effective standard treatment was available, were enrolled. Pts in the ixazomib + rifampin arm received a single 4 mg dose of ixazomib on day 8, plus rifampin 600 mg PO on days 1-14 of a 21-day PK cycle. On day 8, ixazomib and rifampin were administered concomitantly and PK samples were collected over 168 hours post-dose. Pts in the reference arm received a single 4 mg dose of ixazomib on day 1 with PK samples collected over 168 hours post-dose. After completion of the 21-day PK cycle, pts could continue in the study and receive ixazomib on days 1, 8, and 15 of 28-day cycles. Plasma PK parameters were estimated by non-compartmental methods. Geometric mean ratios and 90% confidence intervals (CIs) of PK parameters in the ixazomib + rifampin versus ixazomib alone arms were calculated using an ANOVA model. Treatment-emergent adverse events (TEAEs) were assessed using NCI CTCAE version 4.03. Results Eighteen and 20 pts were enrolled to the ixazomib + rifampin and ixazomib alone arms, respectively. To assess the impact of rifampin on ixazomib PK, data from 16 PK-evaluable pts who received ixazomib + rifampin were compared with data from 14 PK-evaluable pts who received ixazomib alone. Demographics and PK parameters are shown in the Table. At data cut-off (4 August 2014), 15 pts (83%) in the ixazomib + rifampin arm had ≥1 TEAE related to study medication. The most common (≥20%) drug-related TEAEs, regardless of grade, were nausea (39%) and fatigue (28%). Three pts (17%) in the ixazomib + rifampin arm experienced ≥1 grade 3 TEAE. Conclusions The strong CYP3A inducer rifampin produced a 74% decrease in ixazomib total systemic exposure. Systemic treatment with strong CYP3A inducers should be avoided in pts receiving ixazomib. Citation Format: Neeraj Gupta, Michael J. Hanley, Karthik Venkatakrishnan, Alberto Bessudo, Sunil Sharma, Bert O9Neil, Bingxia Wang, Ai-Min Hui, John Nemunaitis. A phase 1 drug-drug interaction study between ixazomib, an oral proteasome inhibitor, and rifampin in patients (pts) with advanced solid tumors. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2015 Nov 5-9; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(12 Suppl 2):Abstract nr B147.