Antibody–drug conjugate, GSK2857916, in relapsed/refractory multiple myeloma: an update on safety and efficacy from dose expansion phase I study

Abstract

Interim analyses of a phase I study with GSK2857916, an antibody–drug conjugate against B cell maturation antigen, have previously reported a 60% overall response and 7.9 months progression-free survival in relapsed/refractory multiple myeloma (MM). We provide updated safety and efficacy results of the BMA117159 trial following an additional 14 months' follow-up. This open-label, first-in-human, phase I study was conducted at nine centres in the USA, Canada and the UK, and included adults with MM and progressive disease after stem cell transplantation, alkylators, proteasome inhibitors, and immunomodulators. In part 1, the recommended dose of 3.4 mg/kg was identified; in part 2, patients received GSK2857916 3.4 mg/kg once every 3 weeks. Selected part 2 safety/tolerability and efficacy endpoints are reported. Twenty-one (60.0%; 95% confidence interval (CI) 42.1–76.1) of 35 patients achieved partial response or better, including two stringent complete responses and three complete responses. The median progression-free survival was 12 months and median duration of response was 14.3 months. Thrombocytopenia and corneal events were commonly reported; no new safety signals were identified. GSK2857916 was well tolerated and demonstrated a rapid, deep and durable response in heavily pre-treated patients with relapsed/refractory MM, consolidating the interim analyses conclusions that GSK2857916 is a promising treatment for these patients.

Treatment Options for Triple-class Refractory Multiple Myeloma

“…A phase I trial investigating monotherapy with the antibody demonstrated a 38.5%% ORR and a median PFS of 6.2 months in those with disease refractory to daratumumab, a proteasome inhibitor and an immunomodulator. 49 Treatments Using Bispecific T-cell Engager Technology. Bispecific T-cell engagers (bispecifics) contain 2 single-chain variable fragments connected by a linker molecule.…”

Monoclonal antibodies in relapsed/refractory myeloma: updated evidence from clinical trials, real-life studies, and meta-analyses

“…Trudel and coworkers conducted the first-in-human phase 1 study with GSK2857916 monotherapy in heavily pre-treated RRMM (DREAMM-1, NCT02064387) [100,101]. In the initial 38 patients, the authors selected the optimal dose of GSK2857916 (3.4 mg/kg Q3 W as a 1-h infusion).…”

Therapeutic Monoclonal Antibodies and Antibody Products: Current Practices and Development in Multiple Myeloma

“…In 2018, the results of a first in-human phase I study investigating GSK2857916, a BCMA-targeting mAb conjugated to the antimitotic agent monomethyl auristatin F (MMAF), in 73 RRMM patients were published. BCMA, a transmembrane receptor required for B cell maturation, was chosen as an optimal target, as it is expressed almost exclusively on MM cells and plasma cells [104][105][106]. In the dose-escalation phase of the study, 38 patients received escalating doses of IV GSK2857916 (0.03-4.6 mg/kg) every 3 weeks.…”

“…The most common treatment-related toxicities were thrombocytopenia (63%; grades 3-4: 26%) and corneal events in terms of blurred vision and photophobia (51%; grades 3-4: 3%). Ocular toxicity was mainly limited to grades 1-2 and was reversible and easily manageable with dose reductions (51% of patients) [104,106]. Because GSK285791 showed high ORR in patients previously treated with anti-CD38 mAbs, a phase I/II clinical trial exploring its efficacy as monotherapy in patients with previous exposure to daratumumab/isatuximab has recently completed enrollment and results will soon be available (NCT03525678).…”