Platform Study of Novel Ruxolitinib Combinations in Myelofibrosis Patients

This open-label, multi-center, Phase Ib/II platform study design consisted of 3 parts. Part 1 was a Phase Ib dose escalation and safety run-in for the 5 novel agents in combination with ruxolitinib to assess safety, tolerability and to confirm a recommended Phase II dose. Dose escalation cohorts were treated with ruxoltinib + siremadlin or ruxolitinib + rineterkib. Safety run-in cohorts were treated with either ruxolitinb + sabatolimab, ruxolitinb + crizanlizumab or ruxolitinib + NIS7913.

Parts 2 and 3 were Phase II selection and expansion, respectively, to assess preliminary efficacy of the combination treatments from Part 1 that were evaluated as safe and tolerable. The number of combination treatment arms opening in Part 2 depended on the results of Part 1. In Part 2, an interim analysis was planned to determine if combination treatment(s) could be expanded in Part 3.

In June 2022, Novartis decided to permanently halt the study enrollment in all ongoing parts (Part 1 and Part 2), and Part 3 (expansion) was not initiated. With Protocol Amendment 8, an extension treatment phase of 12 cycles was added in Part 1 to allow access to the combination treatment for ongoing subjects deriving clinical benefit. In consideration of the enrollment halt, Parts 2 and 3 objectives were not pursued, and Part 1 objectives were updated accordingly.