Related Experiment Video
Updated: Feb 7, 2026
Transduction-Transplantation Mouse Model of Myeloproliferative Neoplasm
Published on: December 22, 2016
Phase 2 study of gandotinib (LY2784544) in patients with myeloproliferative neoplasms
J Berdeja1, F Palandri2, M R Baer3
1Tennessee Oncology, 250 25th Ave N #412, Nashville, TN, 37203, USA.
Background:
The Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs) are associated with increases in janus kinase 2 (JAK2) signaling, often resulting from the JAK2 V617F mutation. LY2784544 (gandotinib) is a potent, selective, small-molecule inhibitor of JAK2 that has potential dose-dependent selectivity for the JAK2 V617F mutation and may inhibit additional JAK2 mutant isoforms in nonclinical testing.
Methods:
A multicenter, single-arm, outpatient phase 2 study evaluated the efficacy, safety, and pharmacokinetics (PK) of gandotinib administered to patients (120 mg once daily) with MPNs, including polycythemia vera (PV), essential thrombocythemia (ET), and myelofibrosis (MF). Between May 2012 and March 2015, 138 patients received at least one dose of study drug.
Findings:
Most frequent Grade 3 or 4 treatment-emergent adverse events that were considered study-drug related were anemia (11.6%), hyperuricemia (3.2%), fatigue (2.9%), diarrhea (2.2%), and thrombocytopenia (2.2%). Overall response rates (ORRs) in patients with JAK2 V617F-mutated PV, ET, and MF were 95%, 90.5%, and 9.1%, respectively, while patients with ET and MF without the JAK2 V617F mutations had ORRs of 43.7% and 0%, respectively.
Interpretations:
LY2784544 demonstrated efficacy in JAK2 V617F-mutated MPNs, including in patients previously on ruxolitinib therapy, who had an ORR of 3.3%. At the 1-year visit, 44% of patients experienced a ≥50% improvement in the MPN-Symptom Assessment Form Total Symptom Score, and 26% of patients had a 50% reduction in Brief Fatigue Inventory score.
Insights
Gandotinib (LY2784544) shows efficacy in treating myeloproliferative neoplasms (MPNs) driven by JAK2 mutations. The drug demonstrated significant response rates and symptom improvement in a phase 2 study.
Area of Science:
- Hematology
- Oncology
- Pharmacology
Background:
- Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs) are linked to increased janus kinase 2 (JAK2) signaling, frequently due to the JAK2 V617F mutation.
- LY2784544 (gandotinib) is a selective JAK2 inhibitor with potential activity against JAK2 V617F and other mutant isoforms.
Purpose of the Study:
- To evaluate the efficacy, safety, and pharmacokinetics of gandotinib in patients with MPNs.
- To assess gandotinib's effectiveness across different MPN subtypes, including polycythemia vera (PV), essential thrombocythemia (ET), and myelofibrosis (MF).
Main Methods:
- A multicenter, single-arm, outpatient phase 2 clinical trial.
- 138 patients with MPNs received gandotinib 120 mg once daily between May 2012 and March 2015.
Main Results:
- Overall response rates (ORRs) were high in JAK2 V617F-mutated PV (95%), ET (90.5%), and MF (9.1%).
- Patients with ET and MF lacking JAK2 V617F mutations had ORRs of 43.7% and 0%, respectively.
- Significant symptom improvement was observed, with 44% experiencing a ≥50% reduction in MPN symptoms and 26% a 50% reduction in fatigue at 1 year.
Conclusions:
- Gandotinib demonstrates efficacy in JAK2 V617F-mutated MPNs, including in patients previously treated with ruxolitinib.
- The drug was generally well-tolerated, with the most frequent Grade 3/4 adverse events including anemia and hyperuricemia.
- Gandotinib shows promise as a treatment option for specific MPN patient populations.
More Related Videos
Related Concept Videos
02:39Phase Diagrams
02:31Phase Transitions
01:15Bioavailability Study Design: Healthy Subjects Versus Patients
02:33Phase Transitions: Sublimation and Deposition
01:28Inductance: Single-Phase And Three-Phase Line
Single-Phase Two-Wire Line:
A single-phase line consists of two solid cylindrical conductors, denoted as x and y. Each conductor carries phasor currents ix and iy, respectively. Given that the sum of these currents is...
01:25Capacitance: Single-Phase And Three-Phase Line
Single-Phase Lines
Consider a single-phase, two-wire transmission line with equal phase spacing energized by a voltage source. One conductor carries a uniform positive charge, while the other carries an equal negative charge. The capacitance C of the line can be derived from the voltage V between the conductors. For a one-meter section of the line, the capacitance is given...