Abstract 565P
Background
Selinexor, a first-in-class, novel oral selective inhibitor of nuclear export which inhibits the Exportin-1 (XPO1) or chromosomal region maintenance 1 (CRM1), had demonstrated synergistic activity with many chemotherapies and conferred antitumor efficacy in multiple cancers in in vivo studies.
Methods
This was an open label, single-center, multi-arm phase Ib study utilizing a "3 + 3” design and a "basket type” expansion. Selinexor with topotecan was employed as one of the 13 parallel arms. Patients with advanced or metastatic solid tumours who were unresponsive or had relapsed following prior systemic therapy or where the addition of selinexor to standard chemotherapy deemed appropriate and acceptable, were eligible.
Results
Fourteen patients with the median age of 60 (range, 21 – 68 years) were treated, and the most common cancer types were gynecological cancers; including ovarian (n=5), endometrial (n=2), and 1 each with fallopian tube and vaginal cancers. All 14 patients had at least one treatment emergent adverse events (TEAE) and 13 patients were evaluable for response. The most prevalent TEAE were followings; anemia (85%), fatigue (78%), thrombocytopenia (71%), hyperglycemia (71%), hyponatremia (64%), nausea (64%), fatigue (61%), hypomagnesemia (57%), and vomiting (57%). The commonest grade ≥ 3 TEAE were hyponatremia (28%), anemia (21%), neutropenia (21%), thrombocytopenia (21%) and leukopenia (14%). Two patients dosed at selinexor 60mg had dose limiting toxicities. One patient had grade 3 nausea and vomiting where other experienced grade 4 neutropenia and thrombocytopenia. A patient with endometrial cancer achieved partial response (7.7%) and treatment to failure (TTF) was 48 weeks whereas six patients (46.1%) had stable disease contributing the clinical benefit rate of 53.8%. TTF ranged from 3 to 74 weeks.
Conclusions
Our study showed that once weekly selinexor in combination with topotecan was viable and showed clinical activity with substantial objective responses and the recommend phase II dose of selinexor was 60 mg once weekly in combination with IV topotecan. Future studies are warranted of once weekly oral selinexor in combiation with once weekly oral topotecan.
Clinical trial identification
NCT02419495.
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Karyopharm.
Disclosure
All authors have declared no conflicts of interest.