POIESIS
Official Title: A Phase 3, Randomized, Double-blind, Add-on Study Evaluating the Safety and Efficacy of Navtemadlin Plus Ruxolitinib vs Placebo Plus Ruxolitinib in JAK Inhibitor-Naïve Patients With Myelofibrosis Who Have a Suboptimal Response to Ruxolitinib
Sponsor: Kartos Therapeutics, Inc.
Principal Investigator: Tsewang Tashi, MD
Conditions: Myelofibrosis
Study Description: POIESIS is a global phase 3 registration study for patients with myelofibrosis whose disease has a suboptimal response following treatment with the JAK inhibitor, ruxolitinib – that is, their spleens remain enlarged, and symptoms persist. The study will compare the efficacy and safety of adding navtemadlin to ruxolitinib versus adding placebo to ruxolitinib.
JAK inhibitors are used in the first line setting for patients with myelofibrosis and are the only approved treatment options. There are currently no approved therapies for patients who have not optimally responded to treatment with a JAK inhibitor. The hope is that navtemadlin may provide additional benefit over and above shrinking the spleen and reducing myelofibrosis-related symptoms (e.g. reducing bone marrow fibrosis and the number of myelofibrosis cancer cells).
There are two parts to this study: Run-in period and Add-on period.
Part 1: Run-in Period
Should you meet the eligibility criteria and have never been treated with a JAK inhibitor, you will enter the run-in period and take ruxolitinib for 18-24 weeks. The dose of ruxolitinib will be determined by your study doctor. If your ruxolitinib treatment is helping to shrink the spleen and reduce symptoms to some degree but is not sufficiently effective (considered “sub-optimal”) and you meet other study criteria, you will proceed to the second part of this study (randomized add-on period). If you respond well (“optimally”), you will not proceed to the second part of this study but may remain on your current ruxolitinib treatment. You will no longer be a participant in the study. Should you not respond at all to treatment with ruxolitinib, you will not proceed to the second part of this study. Your doctor will work with you to determine your treatment after you leave the study.
*Part 2: Add-on Period *
If you meet criteria for the randomized add-on period, you will be assigned to receive either add-on navtemadlin or add-on placebo, while continuing ruxolitinib treatment at the same dose that was established during the run-in period. In the randomized period, 180 patients will be randomized in a 2:1 fashion to receive either navtemadlin (120 patients) or placebo (60 patients). You therefore have a 2 out of 3 chance of receiving navtemadlin. This part of the study is blinded, meaning the patients, doctors and the sponsor will not know which add-on treatment (navtemadlin or placebo) is being taken. Before Treatment Starts All patients will first undergo complete clinical evaluations. Blood samples will be collected, spleen volume will be measured using imaging scans (such as MRI or CT), and patients will fill out questionnaires to assess the severity of their myelofibrosis-related symptoms. Upon consent of study participation and during the study period, these procedures (including but not limited to blood work, spleen imaging and the daily 7-symptom questionnaire) will be ongoing until week 28 of the randomized period or end of treatment, whichever is later .
For both periods of the study (run-in period and add-on period), patients remain on study unless they cannot tolerate the treatment or their disease progresses.
Efficacy Analysis
24 weeks after the start of the add-on period, efficacy will be analyzed by comparing navtemadlin to placebo therapy using two key measures:
Spleen volume reduction by MRI or CT imaging Symptom score reduction by the self-reported daily 7-symptom questionnaire It is very important that MRI/CT imaging appointments are attended, and daily symptom scores are accurately recorded until week 28 or end of treatment, whichever is later.
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