Pelabresib

Current understanding

To be populated as evidence accumulates.

Evidence log

• May 21, 20 — CALR Mutation–Directed Agents and Targeted Therapies Represent Key Research Avenue in MPN Management: cross-connection with selinexor-ruxolitinib-combination: Review co-positions the SENTRY (selinexor+ruxolitinib) Phase 3 spleen-volume win with the MANIFEST-3 pelabresib+ruxolitinib program as the two leading frontline ruxolitinib-add-on combination strategies in MF. (novelty: 3)
• May 22, 20 — All Eyes Are on Novel Combination Therapies and Molecular Targets in MPN at ASH 2025: ASH 2025: 96-week MANIFEST-2 Phase 3 data show durable spleen volume reduction, sustained symptom improvement, and anemia benefit with pelabresib + ruxolitinib in JAK-inhibitor-naive myelofibrosis — strongest long-term efficacy evidence to date for the combination. (novelty: 3)
• January 21 — Zavabresib Earns FDA Orphan Drug Designation in Myelofibrosis: cross-connection with zavabresib-bet-inhibitor-mpn: Zavabresib joins pelabresib as a BET inhibitor being combined with ruxolitinib in MF; pelabresib has Phase 3 data while zavabresib is earlier-stage with FDA Orphan Drug Designation. (novelty: 3)
• May 12, 20 — CALR Mutation–Directed Agents and Targeted Therapies Represent Key Research Avenue in MPN Management: cross-connection with selinexor-ruxolitinib-combination: Review groups SENTRY (selinexor+ruxolitinib) with pelabresib (MANIFEST-2) and imetelstat as the key new trial readouts shaping next-line MPN therapy beyond JAK inhibitor monotherapy. (novelty: 3)
• 2026-04-16 — A Phase 3 Study of Pelabresib (DAK539) and Ruxolitinib in Myelofibrosis (MF): Phase 3 randomized trial (trial-late): pelabresib (BET bromodomain inhibitor) combined with ruxolitinib vs ruxolitinib alone in JAK-inhibitor-naive PMF, PPV-MF, and PET-MF patients — first Phase 3 evaluation of a BET inhibitor in MF and a first-in-class combination strategy at late-stage clinical evaluation. (novelty: 4)
• 2026-04-02 — Study of Pelabresib add-on to Ruxolitinib in Japanese Adult Patients With Myelofibrosis: Trial-early (Phase 1b, open-label): pelabresib add-on to ruxolitinib being evaluated in Japanese adult MF patients for safety, pharmacokinetics, and preliminary efficacy — extends the pelabresib + ruxolitinib combination to a geographically distinct cohort. (novelty: 3)
• 2026-04-01 — Safety and Tolerability Study of INCB057643 in Participants With Myelofibrosis and Other Advanced Myeloid Neoplasms: cross-connection with incb057643-bet-inhibitor: Both are BET bromodomain inhibitors being evaluated in MF in combination with ruxolitinib; INCB057643 represents a second BET inhibitor entering this therapeutic space following pelabresib’s MANIFEST-2 development. (novelty: 3)

Open questions

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