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.

Fig. 1

Study profile. *A completed subject is one who has completed at least one cycle of study treatment and an end of study visit without events causing them to withdraw or discontinue from the study; ^†Analysed for safety and clinical activity of study intervention

Fig. 2

Best responses to GSK2857916. a Maximum percentage change from baseline in M-protein or free light chain. For patients with measurable serum M-protein, serum concentration is shown; for patients with urine M-protein measurements, urine concentrations are shown; and for patients with no available serum or urine M-protein measurements, free light-chain concentrations are shown. b Forest plot of overall response rates by patient subgroup. *Defined as prior cyclophosphamide (CTX) regimen with daratumumab as the only drug in the regimen; ^†defined as prior CTX regimen with daratumumab and other drugs in the regimen; ^‡defined as refractory to bortezomib, carfilzomib, lenalidomide, pomalidomide and daratumumab; ^§a patient is considered as high risk if the subject has any of the following cytogenetics: t(4;14), del17p and t(14;16)

Fig. 3

Response duration and effect of dose modifications. a Duration of study treatment by response. Treatment duration counts the time difference between first dose date and final dose date without accounting for dosing interruptions. Triangles indicate patients remaining on the study. b Dose modifications in responding patients. For each of the 21 responding patients, initial response (partial response or better) is indicated in green, best response in blue, and progressive disease in red. The numbers indicate dose (mg/kg) for each infusion. CR, complete response; NE, not evaluable; PD, progressive disease; PR, partial response; sCR, stringent complete response; SD, stable disease; VGPR, very good partial response

Fig. 4

Kaplan–Meier curves for a progression-free survival and b duration of response in the overall population, and c progression-free survival in patients with prior daratumumab