Selinexor plus ruxolitinib demonstrated “rapid, deep, and sustained spleen responses” in patients with treatment-naïve myelofibrosis, according to results from a phase I trial presented at the American Association for Cancer Research (AACR) Annual Meeting 2023.
“These data suggest that the combination of selinexor and ruxolitinib has the potential to be a transformative therapy for first-line myelofibrosis patients,” Reshma Rangwala, MD, PhD, Chief Medical Officer of Karyopharm Therapeutics Inc, said in a news release issued by the company.
Investigators of the phase I trial assigned 24 patients with treatment-naïve myelofibrosis to receive ruxolitinib plus selinexor 40mg or 60mg once weekly, as of the data cut-off date (February 24, 2023). All patients initiated treatment >24 weeks prior to the data cut-off date. See TABLE 1 for responses across dose levels and patient populations at 12 weeks. See TABLE 2 for responses across dose levels and patient populations at 24 weeks.
“The spleen responses and symptom improvements seen across all patients with the 60mg selinexor dose is very compelling,” the study’s first author, Haris Ali, MD, of the City of Hope Comprehensive Cancer Center, said in the release. “These data suggest this tolerable and unique combination of [Exportin 1] and [Janus kinase] inhibition has the potential to significantly improve these key efficacy measures for first-line myelofibrosis patients.”
Both the 40mg and 60mg doses of selinexor were “generally well tolerated and manageable,” allowing most patients to remain on therapy for up to 68 weeks, as of the data cut-off date, officials said in the release.
The most common treatment-emergent adverse event, regardless of grade, was nausea, reported in 70% of the patients who received the 40-mg dose, and in 78.6% of those who received 60 mg. Most (75%) nausea events were grade 1, were “mostly transient,” and did not lead to treatment-related discontinuations, according to the release. The rates and grades of nausea were reduced in patients who received prophylactic antiemetics.
The other common treatment-emergent adverse events of any grade were anemia, which occurred in 40% of patients receiving the 40 mg dose and in 64.3% of those receiving 60 mg; and fatigue, which occurred in 60% of patients receiving 40 mg, and in 57.1% of those receiving 60 mg. Most events were grade 1 to grade 2, according to the release.
The most common treatment-emergent adverse events of grade 3 or higher in patients who received the 40-mg dose in combination with ruxolitinib were anemia (30%), thrombocytopenia (10%), and neutropenia (20%). The most common treatment-emergent adverse events of grade 3 or higher in patients who received the 60-mg dose in combination with ruxolitinib were also anemia (42.9%), thrombocytopenia (28.6%), and neutropenia (7.1%).
There were two treatment-related discontinuations, one due to thrombocytopenia and one due to peripheral neuropathy.
A phase III trial of the treatment is being planned.
“We look forward to building upon these findings as we plan the initiation of a pivotal phase III study in front-line myelofibrosis later this quarter,” Dr. Rangwala said in the release.
Source: Karyopharm Therapeutics Inc, April 2023