Abstract 554P
Background
Selinexor is a first-in-class novel, oral potent selective inhibitor of nuclear export which blocks the transport protein called Exportin-1. Carboplatin+ Taxol (CT) is one of the standard chemotherapy regimens used in various tumour types. Preclinical models have suggested that selinexor and CT exerts antitumor activity in multiple malignancies.
Methods
This was an open label, single-center, multi-arm phase Ib study utilizing a “3 + 3” design and a “basket type” expansion. CT + selinexor 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
Of 13 patients treated, 12 patients were evaluable for response. The most common cancers were breast (n=4), esophageal (n=2), ovarian (n=2) and non-small cell lung cancers (n=2). All 13 patients had at least one treatment-emergent adverse events (TEAE) and the commonest TEAE were anemia (84%), neutropenia (84%), leukopenia (84%), thrombocytopenia (84%), fatigue (61%), elevated AST or ALT (61%), nausea (53%), hypomagnesemia (53%), and peripheral motor or sensory neuropathy (53%). The most prevalent grade ≥ 3 TEAE were neutropenia (69%), thrombocytopenia (53%), leukopenia (46%), and anemia (15%). One patient at 60mg once weekly had experienced DLT with grade 4 neutropenia lasting >7 days. Partial response was noted in 4 patients (33.3%) in patients with esophageal (n=2), 1 patient each with breast and ovarian cancer. Five patients (41.7%) achieved stable disease and the clinical benefit rate was 75%. Majority of patients (84%), including 3 patients who had PR, had prior exposure to carboplatin and/ or paclitaxel. Treatment time to failure (TTF) ranged from 10 to 148 weeks and TTF for patients with PR was from 18 to 23 weeks.
Conclusions
Oral selinexor can be safely combined with CT and the RP2D was 60 mg once weekly in combination with CT. The combination conferred appreciable clinical activity with durable objective responses which should further be explored in tumour types for which CT is used as standard of care.
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.