Protein Inhibitor INCB039110 Appears Active in Myelofibrosis
CancerConnect News: In early analysis from a Phase II clinical trial, the JAK1 inhibitor INCB039110 appears to improve symptoms in patients with myelofibrosis. These findings were presented at the 56th American Hematological Society Annual Meeting and Exposition, December 6–9, 2014, in San Francisco, California.
Myelofibrosis is a type of blood cancer known as a myeloproliferative neoplasm. It involves the abnormal development and function of bone marrow cells that produce blood cells and leads to the formation of scar tissue in the bone marrow. This can cause anemia, enlargement of the spleen and liver, fatigue, and other problems. In some patients with myelofibrosis, the condition progresses to acute myeloid leukemia.
Proteins known as JAK1 and JAK2 may play a role in the development of MPNs, including myelofibrosis, by causing the body to make the wrong number of blood cells. Drugs that suppress JAK1 and JAK2 are used to treat different forms of MPN by reducing the number of abnormal number of blood cells associated with these disorders. JAK1/JAK2 inhibitors can, however, result in too much suppression of the bone marrow’s production of blood cells, or myelosuppression—a condition that can negatively impact patient health and quality of life.
The investigational agent INCB039110 targets and suppresses JAK1 only (versus JAK1 and JAK2). The goal of suppressing JAK1 alone is to improved symptoms of myelofibrosis with less myelosuppression.
Researchers with a Phase II trial of INCB039110 recently reported their findings at three- and six-month analyses. The study included patients with different types of MPN, including myelofibrosis.
On a daily basis, participants completed forms that assessed the severity of their myelofibrosis symptoms. Spleen volume, a marker of disease activity in MPN, was measured at the start of the study and again at three and six months. The researchers were primarily looking for a 50% or greater reduction in symptoms (including night sweats, itchiness, abdominal discomfort, pain under left ribs, early satiety, and bone/muscle pain) between the start of the study and the three-month checkpoint. They were also monitoring for symptom reduction at six months and safety of INCB039110.
The 87 study participants were divided into three separate groups, each with a different dose of INCB039110: 100 mg twice daily (10 patients), 200 mg twice daily (45 patients), and 600 mg once daily (32 patients).
Symptoms overall were similarly improved between the 200-mg and 600-mg groups. Spleen volume was also modestly reduced in these two groups.
At six months there was not a trend toward excessive myelosuppression. Levels of hemoglobin (a protein in red blood cells that carries oxygen) were increased for patients in the 200- and 600-mg groups who did not require transfusions: by 5.6% and 8.6%, respectively.
The most common non-blood-related adverse events tended to be mild to moderate and included fatigue, nausea, upper respiratory tract infection, constipation, diarrhea, and cough. A portion of patients (33%) developed new or worsening anemia, and another portion (24%) developed moderate thrombocytopenia (low platelet count).
According to these findings, treatment with the JAK1 inhibitor INCB039110 can improve symptoms in patients with myelofibrosis, as well as moderately decrease spleen size. INCB039110 also appears to be effective without causing excessive levels of myelosuppression over a six-month period. These results show the potential for a JAK1 inhibitor to effectively treat symptoms of myelofibrosis without the complications myelosuppression associated with JAK1/JAK2 inhibitors.
Reference: Mascarenhas JO, Talpaz M, Gupta V, et al. Primary Analysis Results from an Open-Label Phase II Study of INCB039110, a Selective JAK1 Inhibitor, in Patients with Myelofibrosis. Program and Abstracts of the 56th American Hematological Society Annual Meeting and Exposition; December 6–9, 2014; San Francisco, California. Abstract 714.
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