Karyopharm Therapeutics Inc. (NASDAQ:KPTI) has announced that it has dosed the first patient in its Phase 1/2 clinical trial for the evaluation of oral selinexor. The study is meant to evaluate the combination of selinexor and the standard care therapies in recurrent or newly diagnosed glioblastoma (GBM) patients.
Study to enrol 400 patients in the US, Europe, and Israel
The company expects to enroll around 400 patients globally for the study across the US, Europe, and Israel. Selinexor, which is a selective inhibitor of a nuclear export compound that blocks the XPO1 cellular protein, works to regulate tumor activity suppressor proteins as well as other cancer oncoproteins. XPO1 could be an important proprietary target in treating GBM patients. This is because it is regularly overexpressed in GBM as well as high-grade gliomas. Also, the level of XPO1 overexpression is correlated with high tumor grade as well as the overall survival of patients.
According to nonclinical studies, selinexor has shown strong anti-GBM effect as a monotherapy and is and can work well in combination with temozolomide, radiation, and lomustine. Equally, in previous preclinical studies, selinexor has shown that it can cross the blood-brain barrier with significant intra-tumoral penetration. It has also demonstrated single-agent efficacy offering durable response as well as disease stabilization, especially in heavily penetrated patients.
Selinexor study to be carried in two phases
Karyopharm’s phase 1/2 study (NCT04421378/XPORT-GBM-029) will be a multicentre randomized study that will be carried in two stages. The first phase will be a dose-finding study, which will be followed by a randomized second phase efficacy study. The study has been designed to evaluate three different regimen combinations that will be on three arms. The first and second (A&B) arms will be for patients with newly diagnosed GBM, and the third (C) arm will be for those with recurrent GBM.
Arms A & B will evaluate the combination of selinexor and radiation without or with temozolomide, while Arm C will evaluate selinexor in combination with lomustine. The primary endpoints will be PFS in newly diagnosed GBM patients and OS in recurrent GBM patients.