0000000000993881
AUTHOR
Song Mu
A phase 1b, dose-finding study of ruxolitinib plus panobinostat in patients with myelofibrosis.
7022^ Background: Myelofibrosis (MF) is a myeloproliferative neoplasm characterized by dysregulation of the Janus kinase (JAK) pathway resulting in bone marrow fibrosis, splenomegaly, and debilitat...
Efficacy, Safety, and Confirmation of the Recommended Phase 2 Starting Dose of the Combination of Ruxolitinib (RUX) and Panobinostat (PAN) in Patients (Pts) with Myelofibrosis (MF)
Abstract BACKGROUND: MF is a myeloproliferative neoplasm characterized by bone marrow (BM) fibrosis, splenomegaly, and debilitating constitutional symptoms. RUX is a potent JAK1/JAK2 inhibitor that has demonstrated superiority in spleen volume reduction, symptom improvement, and survival in the phase 3 COMFORT studies compared with placebo and best available therapy. PAN, a potent pan-deacetylase inhibitor, inhibits JAK signaling by disrupting the interaction between JAK2 and heat shock protein 90, a protein chaperone. PAN has demonstrated reductions in splenomegaly and improvement of BM fibrosis in phase 1/2 studies. The combination of RUX and PAN demonstrated synergistic activity in precl…
Efficacy, Safety, and Confirmation of the Recommended Phase 2 Dose of Ruxolitinib Plus Panobinostat in Patients with Intermediate or High-Risk Myelofibrosis
Abstract Background: Myelofibrosis (MF) is a clonal neoplastic disease resulting in bone marrow fibrosis, splenomegaly, and debilitating constitutional symptoms. The Janus kinase (JAK) pathway is often dysregulated in MF, and agents targeting this pathway have demonstrated efficacy in this disease. Ruxolitinib (RUX), a potent JAK1/JAK2 inhibitor, demonstrated superiority in spleen volume reduction, symptom improvement, and survival compared with the control arm in the phase III COMFORT-I and COMFORT-II studies. Panobinostat (PAN), a potent pan-deacetylase inhibitor (pan-DACi), inhibits JAK signaling through disruption of the interaction of JAK2 with the protein chaperone heat shock protein …
PARALLEL 303: Phase 2 randomized study of pamiparib vs placebo as maintenance therapy in patients (pts) with inoperable locally advanced or metastatic gastric cancer that responded to platinum-based first-line (1L) chemotherapy.
3109 Background: A subset of gastric cancers exhibits platinum sensitivity and genomic instability that is characteristic of homologous recombination deficiency (HRD). Cells with HRD are sensitive to poly (ADP-ribose) polymerase (PARP) inhibition. PARP inhibitor maintenance therapy following platinum-based chemotherapy has been a successful treatment strategy in pts with ovarian cancer. Pamiparib is an orally administered selective PARP protein 1 and 2 (PARP1/2) inhibitor that has shown potent DNA-PARP trapping activity and crosses the blood brain barrier in preclinical studies. In early phase clinical studies (NCT02361723; NCT03333915), pamiparib showed an acceptable safety profile and pr…
A Phase 1b, Dose-Finding Study Of Ruxolitinib Plus Panobinostat In Patients With Primary Myelofibrosis (PMF), Post–Polycythemia Vera MF (PPV-MF), Or Post–Essential Thrombocythemia MF (PET-MF): Identification Of The Recommended Phase 2 Dose
Abstract Background Myelofibrosis (MF) is a myeloproliferative neoplasm associated with progressive, debilitating symptoms that impact patient quality of life (QoL) and reduce survival. Ruxolitinib (RUX), a potent dual JAK1/JAK2 inhibitor, demonstrated superiority in spleen volume and symptom reduction, improved health-related QoL measures, and prolonged survival compared with traditional therapies or placebo in the phase 3 COMFORT studies. Panobinostat (PAN) is a potent oral pan-deacetylase inhibitor (DACi) that inhibits JAK pathway signaling through increased acetylation of the JAK2 protein chaperone HSP90. In phase 1/2 studies in MF, PAN has shown reduction in splenomegaly and JAK2 V617F…