The U.S. Food and Drug Administration (FDA) granted breakthrough-therapy designation to the B-cell maturation antigen antibody-drug conjugate GSK2857916 for relapsed/refractory multiple myeloma (MM). The drug is indicated for patients for whom at least three prior lines of therapy have failed, including an anti-CD38 antibody, and whose disease is refractory to a proteasome inhibitor and an immunomodulatory agent.
The FDA's decision was based on results from an open-label, dose-escalation and -expansion, phase I study of 24 patients with relapsed/refractory MM who were treated at eight dose levels. GSK2857916 is administered every three weeks with no mandatory prophylaxis for infusion-related reactions (IRRs).
Treatment responses included one minimal response (MR) at the 0.24 mg/kg dose and one very good PR, three PRs, and one MR at doses â‰¥0.96 mg/kg. The clinical benefit rate (including unconfirmed responses) was 25 percent.
Seven patients (29%) had adverse cytogenetics, including del17p13 or t(4;14). Twenty-three patients (96%) experienced AEs, the most common of which were nausea (42%), fatigue (38%), anemia (29%), chills (29%), pyrexia (29%), thrombocytopenia (29%), dry eye (21%), and hypercalcemia (21%). Eight serious AEs were reported among six patients, including one incidence of unresolved limbal stem cell dysfunction that was deemed treatment related. No AEs led to treatment discontinuation, but four patients required dose reductions because of ocular toxicity, corneal disorder/ocular toxicity, dry eye, and keratitis. Seven patients (29%) experienced IRRs, all of which were grade 1 or 2 and occurred during the first treatment dose.
Fourteen patients discontinued treatment because of disease progression. One patient completed all 16 scheduled cycles, and eight patients were still undergoing treatment at the time of analysis.
GSK2857916 previously received orphan-drug designation for relapsed/refractory MM.
Source: GlaxoSmithKline press release, November 2, 2017.