Abstract CT252: A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study of Ruxolitinib Plus Parsaclisib in Patients with JAK- and PI3K-Inhibitor Treatment-Naïve Myelofibrosis
Bibliographic record
Abstract
Abstract Background: Ruxolitinib (JAK1/JAK2 inhibitor) significantly improves outcomes in patients with myelofibrosis (MF); however, a subset of patients may experience a suboptimal response. Recent phase 2 data showed that addition of PI3Kδ inhibitor parsaclisib to ruxolitinib monotherapy resulted in additional alleviation of MF symptoms and splenomegaly in patients with MF (Yacoub. EHA2020. S216). This phase 3, randomized, double-blind study (INCB 50465-313; NCT04551066), evaluates the combination of ruxolitinib and parsaclisib in patients with MF who are naïve to Janus kinase (JAK) and PI3K inhibitor therapies. Methods: Eligible patients are aged ≥18 years with a diagnosis of primary MF, post-polycythemia vera MF, or post-essential thrombocythemia MF, have a Dynamic International Prognostic Scoring System (DIPSS; Passamonti. Blood. 2010;115:1703-1708) risk category of at least Intermediate (INT)-1, palpable spleen ≥5 cm below left subcostal margin, total symptom score ≥10 at screening, ECOG PS 0-2, and life expectancy ≥24 weeks. Patients will be excluded if they previously received therapy with any JAK inhibitor, any PI3K inhibitor, any experimental or standard drug therapy for MF within 3 months of first study dose and/or lack of recovery from all toxicities related to previous therapies to grade ≤1, have recent history of inadequate bone marrow reserve (eg, platelet count <50×109/L) or have inadequate liver or renal function at screening. Approximately 440 patients will be randomized (1:1) to ruxolitinib plus parsaclisib 5 mg QD or ruxolitinib plus matching placebo, with stratification at randomization by DIPSS risk category (high vs INT-2 vs INT-1) and platelet count (≥100×109/L vs 50 to <100×109/L inclusive). Treatment will begin on Day 1, with starting ruxolitinib dose level determined by baseline platelet count, and will continue as long as treatment is tolerated and discontinuation criteria are not met. When the last enrolled patient has completed 24 weeks of treatment, the study will be unblinded and patients randomized to ruxolitinib plus placebo who have adequate hematology parameters will be able to crossover to receive parsaclisib together with continued ruxolitinib. The primary objective is the evaluation and comparison of spleen volume at Week 24 for patients who received ruxolitinib plus parsaclisib versus ruxolitinib plus placebo. Secondary objectives include evaluation and comparison of patient-reported MF symptoms, overall survival, time to onset and duration of response in spleen volume, and safety and tolerability for ruxolitinib plus parsaclisib versus ruxolitinib plus placebo. Sites are opening across the US, Canada, EU, and Asia. Citation Format: Abdulraheem Yacoub, Sue Erickson-Viitanen, Feng Zhou, Albert Assad. A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study of Ruxolitinib Plus Parsaclisib in Patients with JAK- and PI3K-Inhibitor Treatment-Naïve Myelofibrosis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr CT252.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 0.001 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.003 | 0.002 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.002 | 0.003 |
| Insufficient payload (model declined to judge) | 0.013 | 0.002 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".