In humans, early clinical trials (phase I) have been conducted in non-Hodgkin lymphoma, blast crisis, and a wide range of advanced or refractory solid tumors, including colon cancer, head and neck cancer, melanoma, ovarian cancer, and prostate cancer. Compassionate use in patients with acute myeloid leukemia has also been reported.The pivotal clinical trial which served to support approval of selinexor for people with relapsed/refractory multiple myeloma was an open-label study of 122 patients known as the STORM trial. In all of the enrolled patients, patients had been treated with a median of seven prior treatment regimens including conventional chemotherapy, targeted therapy with bortezomib, carfilzomib, lenalidomide, pomalidomide, and a monoclonal antibody (daratumumab or isatuximab); nearly all had also undergone hematopoietic stem cell transplantation but had disease that continued to progress. The overall response rate was 26%, including two stringent complete responses; 39% of patients had a minimal response or better. The median duration of response was 4.4 months, median progression-free survival was 3.7 months, and median overall survival was 8.6 months.As of 2019, phase I/II and III trials are ongoing, including the use of selinexor in other cancers and in combinations with other drugs used for multiple myeloma.In November 2020, results from the multi-center, Phase III, randomized study (NCT03110562) which evaluated 402 participants with relapsed or refractory multiple myeloma who had received one to three prior lines of therapy were published in The Lancet.
Most adverse reactions were manageable with dose modifications and/or standard supportive care. The most common non-hematologic adverse reactions were fatigue (59%), nausea (50%), decreased appetite (35%), and diarrhea (32%) and were mostly Grade 1 and 2 events. The most common Grade 3 and 4 adverse reactions were thrombocytopenia (43%), lymphopenia (38%), fatigue (28%) and anemia (17%).The most common adverse reactions (incidence ≥20%) in people with diffuse large B-cell lymphoma (DLBCL), excluding laboratory abnormalities, were fatigue, nausea, diarrhea, appetite decrease, weight decrease, constipation, vomiting, and pyrexia. Grade 3-4 laboratory abnormalities in ≥15% were thrombocytopenia, lymphopenia, neutropenia, anemia, and hyponatremia. Serious adverse reactions occurred in 46% of people, most often from infection. Thrombocytopenia was the leading cause of dose modifications. Gastrointestinal toxicity developed in 80% of people and any grade hyponatremia developed in 61%. Central neurological adverse reactions occurred in 25% of people, including dizziness and mental status changes.The prescribing information provides warnings and precautions for thrombocytopenia, neutropenia, gastrointestinal toxicity, hyponatremia, serious infection, neurological toxicity, and embryo-fetal toxicity. Mechanism of action
Like other selective inhibitors of nuclear export (SINEs), selinexor works by binding to exportin 1 (also known as XPO1 or  CRM1). XPO1 is a karyopherin which performs nuclear transport of several proteins, including tumor suppressors, oncogenes, and proteins involved in governing cell growth,  from the cell nucleus to the cytoplasm; it is often overexpressed and its function misregulated in several types of cancer.