Phase 1b/2 selinexor XPO1 (SINE) inhibitor plus carfilzomib proteasome inhibitor in RRMM

This Phase 1b/2, open-label combination study evaluates selinexor (Karyopharm; an oral XPO1/exportin-1 selective inhibitor of nuclear export) with carfilzomib (Amgen; selective, irreversible proteasome inhibitor), isatuximab delivered subcutaneously via an investigational on-body delivery system (Sanofi; CD38-directed cytolytic monoclonal antibody), and dexamethasone (glucocorticoid) in relapsed and/or relapsed/refractory multiple myeloma after at least 1 prior line. The Phase 1b safety run-in (about 6–12 patients) is used to establish tolerability and a recommended Phase 2 dose, with a built-in option to de-escalate selinexor (e.g., 40 mg down to 20 mg) if prespecified toxicity is reached. The Phase 2 expansion enrolls up to ~50 patients, including a high-risk cohort, focusing on safety plus preliminary efficacy in measurable active disease. The standout angle is the delivery innovation: shifting isatuximab from IV infusion to a wearable SC system while layering a mechanistically distinct oral agent (XPO1 inhibition) onto a proteasome inhibitor + anti-CD38 backbone. In this setting, today’s care is sequential multi-drug triplets/quadruplets using anti-CD38 antibodies, proteasome inhibitors, IMiDs, and steroids, with BCMA- or GPRC5D-directed therapies in later lines depending on prior exposure and eligibility.