Antibody–drug conjugate, GSK2857916, in relapsed/refractory multiple myeloma: An update on safety and efficacy from dose expansion phase I study Journal Article
| Authors: | Trudel, S.; Lendvai, N.; Popat, R.; Voorhees, P. M.; Reeves, B.; Libby, E. N.; Richardson, P. G.; Hoos, A.; Gupta, I.; Bragulat, V.; He, Z.; Opalinska, J. B.; Cohen, A. D. |
| Article Title: | 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. © 2019, The Author(s). |
| Keywords: | adult; clinical article; treatment response; aged; constipation; fatigue; neutropenia; diarrhea; drug efficacy; drug safety; hypertension; side effect; treatment duration; follow up; progression free survival; multiple myeloma; neutrophil count; anemia; nausea; thrombocytopenia; deep vein thrombosis; stem cell transplantation; hematuria; alanine aminotransferase blood level; arthralgia; aspartate aminotransferase blood level; backache; chill; coughing; dyspnea; febrile neutropenia; fever; gamma glutamyl transferase blood level; pneumonia; salmonellosis; alanine aminotransferase; alkaline phosphatase; aspartate aminotransferase; hypokalemia; multicenter study; urinary tract infection; brain disease; cataract; retina detachment; open study; creatine kinase; lactate dehydrogenase; alkaline phosphatase blood level; bacteremia; clinical effectiveness; headache; phase 1 clinical trial; gamma glutamyltransferase; lung infection; dry eye; pericardial effusion; cholecystitis; disease exacerbation; lactate dehydrogenase blood level; photophobia; respiratory tract infection; upper respiratory tract infection; blurred vision; appendicitis; keratitis; eye pain; rib fracture; gastroenteritis; humerus fracture; decreased appetite; falling; sinusitis; contusion; acute cholecystitis; lower respiratory tract infection; faintness; infusion related reaction; human; male; female; article; tooth pain; daratumumab; keratopathy; gsk 2857916 |
| Journal Title: | Blood Cancer Journal |
| Volume: | 9 |
| Issue: | 4 |
| ISSN: | 2044-5385 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2019-03-20 |
| Start Page: | 37 |
| Language: | English |
| DOI: | 10.1038/s41408-019-0196-6 |
| PUBMED: | 30894515 |
| PROVIDER: | scopus |
| PMCID: | PMC6426965 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 May 2019 -- Source: Scopus |
