This is an open-label, nonrandomized, Phase 1/2 study to evaluate the safety and tolerability, the PK, the PD, and the efficacy (antianemic activity) of INCB000928 administered alone or in combination with ruxolitinib in participants with MF who are transfusion-dependent or presenting with symptomatic anemia.
INCB000928 tablets will be administered orally at a starting dose of 50 mg QD in the TGA participant population (monotherapy). The starting dose in combination with ruxolitinib will be determined based on the data from the monotherapy dose escalation. One cycle will be defined as 28 consecutive days; treatment will consist of repeating 28-day cycles. The dose-escalation stages will use a BOIN design to determine the MTD.
For TGB only, the recommended dose for expansion of INCB000928 when administered in combination with ruxolitinib will be determined based on the dose-escalation stage results; efficacy will also be explored. The INCB000928 dose will be escalated using an open-label BOIN design in each defined population, and a safe and tolerable dose (RDE) will be determined in the dose-escalation stages. This RDE will be further explored in the expansion stages for TGB only. Dose escalation and de-escalation will follow the BOIN design algorithm.
For TGB only (Part 2), the expansion stages will aim at further assessing the safety and tolerability of INCB000928, the PK and PD, and determining its antianemic activity when combined with ruxolitinib in participants with transfusion-dependent or symptomatic anemia due to myeloproliferative disorders.