Karyopharm Therapeutics has started a registration-directed Phase IIb trial (SADAL) of its lead drug candidate Selinexor (KPT-330), in patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL).
Selinexor is one of the company’s new, oral selective inhibitor of nuclear export/SINE compounds.
Around 200 patients in about 90 sites worldwide will be enrolled in the trial, which is evaluating selinexor as a single agent in combination with dexamethasone for supportive care.
The company received orphan drug designation from the US Food and Drug Administration (FDA) and European Medicines Agency (EMA) for Selinexor to treat patients with DLBCL.
The open-label, randomised, multi-centre Phase IIb trial will evaluate the safety and efficacy of 100mg versus 60mg Selinexor in combination with 8mg-12mg dexamethasone for supportive care, in these patients.
The trial would take about two years to complete and is expected to support accelerated regulatory approval.
Karyopharm president and chief scientific officer Sharon Shacham said: "This study in DLBCL is the third registration-directed study initiated for Selinexor this year.
"In June we initiated a registration-directed study evaluating Selinexor in patients with acute myeloid leukemia and in November we initiated a registration-directed study evaluating Selinexor in patients with Richter’s Transformation.
"We are very encouraged by the responses and durability demonstrated to-date in patients with DLBCL and look forward to continuing to evaluate Selinexor in this patient population.
"Our goal is to accelerate development of Selinexor in severe hematologic indications with great unmet need while simultaneously broadening the scope of our development efforts in other hematologic and solid tumour indications."
Overall response rate (ORR) is the primary endpoint of the trial, which was designed in consultation with the FDA and on the basis of data from the company’s ongoing Phase I trial of selinexor in patients with advanced hematologic malignancies.
In the ongoing Phase I trial, as of 1 December, data from heavily pre-treated patients with relapsed/refractory DLBCL and other types of non-Hodgkin’s lymphoma (NHL) show that median duration of response (DOR) of about seven months for Selinexor in patients with NHL.
The data also shows 40% ORR in aggressive B-cell NHL, including four of ten partial responses (PRs), in patients treated with high-dose Selinexor, and a 37% ORR, including four complete responses (CRs) and three PRs, in patients treated with mid-dose Selinexor.
The trial also showed that anti-tumour activity across DLBCL subtypes, including 36% and 40% ORRs in patients known to have the Germinal Center B-Cell like (GCB) or non-GCB subtypes, respectively, as well as a 50% ORR in four patients with ‘double-hit’ DLBCL.