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Phase IIa study of the CD19 antibody MOR208 in patients with relapsed or refractory B-cell non-Hodgkin’s lymphoma

BACKGROUND: This two-stage, phase IIa study investigated the antitumor activity and safety of MOR208, an Fc-engineered, humanized, CD19 antibody, in patients with relapsed or refractory (R-R) B-cell non-Hodgkin’s lymphoma (NHL). CD19 is broadly expressed across the B-lymphocyte lineage, including in...

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Autores principales: Jurczak, W, Zinzani, P L, Gaidano, G, Goy, A, Provencio, M, Nagy, Z, Robak, T, Maddocks, K, Buske, C, Ambarkhane, S, Winderlich, M, Dirnberger-Hertweck, M, Korolkiewicz, R, Blum, K A
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5961010/
https://www.ncbi.nlm.nih.gov/pubmed/29444231
http://dx.doi.org/10.1093/annonc/mdy056
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author Jurczak, W
Zinzani, P L
Gaidano, G
Goy, A
Provencio, M
Nagy, Z
Robak, T
Maddocks, K
Buske, C
Ambarkhane, S
Winderlich, M
Dirnberger-Hertweck, M
Korolkiewicz, R
Blum, K A
author_facet Jurczak, W
Zinzani, P L
Gaidano, G
Goy, A
Provencio, M
Nagy, Z
Robak, T
Maddocks, K
Buske, C
Ambarkhane, S
Winderlich, M
Dirnberger-Hertweck, M
Korolkiewicz, R
Blum, K A
author_sort Jurczak, W
collection PubMed
description BACKGROUND: This two-stage, phase IIa study investigated the antitumor activity and safety of MOR208, an Fc-engineered, humanized, CD19 antibody, in patients with relapsed or refractory (R-R) B-cell non-Hodgkin’s lymphoma (NHL). CD19 is broadly expressed across the B-lymphocyte lineage, including in B-cell malignancies, but not by hematological stem cells. PATIENTS AND METHODS: Patients aged ≥18 years, with R-R NHL progressing after ≥1 prior rituximab-containing regimen were enrolled into subtype-specific cohorts: diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), other indolent (i)NHL and mantle cell lymphoma (MCL). Treatment was MOR208, 12 mg/kg intravenously, weekly, for 8 weeks. Patients with at least stable disease could continue treatment for an additional 4 weeks. Those with a partial or complete response after 12 weeks could receive extended MOR208 treatment (12 mg/kg, either monthly or every second week) until progression. The primary end point was overall response rate. RESULTS: Ninety-two patients were enrolled: DLBCL (n = 35), FL (n = 34), other iNHL (n = 11) and MCL (n = 12). Responses were observed in DLBCL, FL and other iNHL cohorts (26%, 29% and 27%, respectively). They lasted ≥12 months in 5/9 responding patients with DLBCL, 4/9 with FL and 2/3 with other iNHL. Responses in nine patients are ongoing (>26 months in five instances). Patients with rituximab refractory disease showed a similar response rate and progression-free survival time to patients with non-refractory disease. The most common adverse events (any grade) were infusion-related reactions (12%) and neutropenia (12%). One patient experienced a grade 4 infusion-related reaction and eight patients (9%) experienced grade 3/4 neutropenia. No treatment-related deaths were reported. CONCLUSIONS: MOR208 monotherapy demonstrated promising clinical activity in patients with R-R DLBCL and R-R FL, including in patients with rituximab refractory tumors. These efficacy data and the favorable safety profile support further investigation of MOR208 in phase II/III combination therapy trials in R-R DLBCL. CLINICALTRIALS.GOV NUMBER: NCT01685008.
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spelling pubmed-59610102018-06-06 Phase IIa study of the CD19 antibody MOR208 in patients with relapsed or refractory B-cell non-Hodgkin’s lymphoma Jurczak, W Zinzani, P L Gaidano, G Goy, A Provencio, M Nagy, Z Robak, T Maddocks, K Buske, C Ambarkhane, S Winderlich, M Dirnberger-Hertweck, M Korolkiewicz, R Blum, K A Ann Oncol Original Articles BACKGROUND: This two-stage, phase IIa study investigated the antitumor activity and safety of MOR208, an Fc-engineered, humanized, CD19 antibody, in patients with relapsed or refractory (R-R) B-cell non-Hodgkin’s lymphoma (NHL). CD19 is broadly expressed across the B-lymphocyte lineage, including in B-cell malignancies, but not by hematological stem cells. PATIENTS AND METHODS: Patients aged ≥18 years, with R-R NHL progressing after ≥1 prior rituximab-containing regimen were enrolled into subtype-specific cohorts: diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), other indolent (i)NHL and mantle cell lymphoma (MCL). Treatment was MOR208, 12 mg/kg intravenously, weekly, for 8 weeks. Patients with at least stable disease could continue treatment for an additional 4 weeks. Those with a partial or complete response after 12 weeks could receive extended MOR208 treatment (12 mg/kg, either monthly or every second week) until progression. The primary end point was overall response rate. RESULTS: Ninety-two patients were enrolled: DLBCL (n = 35), FL (n = 34), other iNHL (n = 11) and MCL (n = 12). Responses were observed in DLBCL, FL and other iNHL cohorts (26%, 29% and 27%, respectively). They lasted ≥12 months in 5/9 responding patients with DLBCL, 4/9 with FL and 2/3 with other iNHL. Responses in nine patients are ongoing (>26 months in five instances). Patients with rituximab refractory disease showed a similar response rate and progression-free survival time to patients with non-refractory disease. The most common adverse events (any grade) were infusion-related reactions (12%) and neutropenia (12%). One patient experienced a grade 4 infusion-related reaction and eight patients (9%) experienced grade 3/4 neutropenia. No treatment-related deaths were reported. CONCLUSIONS: MOR208 monotherapy demonstrated promising clinical activity in patients with R-R DLBCL and R-R FL, including in patients with rituximab refractory tumors. These efficacy data and the favorable safety profile support further investigation of MOR208 in phase II/III combination therapy trials in R-R DLBCL. CLINICALTRIALS.GOV NUMBER: NCT01685008. Oxford University Press 2018-05 2018-02-09 /pmc/articles/PMC5961010/ /pubmed/29444231 http://dx.doi.org/10.1093/annonc/mdy056 Text en © The Author(s) 2018. Published by Oxford University Press on behalf of the European Society for Medical Oncology. http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Original Articles
Jurczak, W
Zinzani, P L
Gaidano, G
Goy, A
Provencio, M
Nagy, Z
Robak, T
Maddocks, K
Buske, C
Ambarkhane, S
Winderlich, M
Dirnberger-Hertweck, M
Korolkiewicz, R
Blum, K A
Phase IIa study of the CD19 antibody MOR208 in patients with relapsed or refractory B-cell non-Hodgkin’s lymphoma
title Phase IIa study of the CD19 antibody MOR208 in patients with relapsed or refractory B-cell non-Hodgkin’s lymphoma
title_full Phase IIa study of the CD19 antibody MOR208 in patients with relapsed or refractory B-cell non-Hodgkin’s lymphoma
title_fullStr Phase IIa study of the CD19 antibody MOR208 in patients with relapsed or refractory B-cell non-Hodgkin’s lymphoma
title_full_unstemmed Phase IIa study of the CD19 antibody MOR208 in patients with relapsed or refractory B-cell non-Hodgkin’s lymphoma
title_short Phase IIa study of the CD19 antibody MOR208 in patients with relapsed or refractory B-cell non-Hodgkin’s lymphoma
title_sort phase iia study of the cd19 antibody mor208 in patients with relapsed or refractory b-cell non-hodgkin’s lymphoma
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5961010/
https://www.ncbi.nlm.nih.gov/pubmed/29444231
http://dx.doi.org/10.1093/annonc/mdy056
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