A PHASE IIA STUDY OF SINGLE-AGENT MOR208, AN FC-OPTIMIZED ANTI-CD19 ANTIBODY, IN PATIENTS WITH RELAPSED OR REFRACTORY B-CELL NON-HODGKIN’S LYMPHOMA
Author(s): ,
Wojciech Jurczak
Affiliations:
Jagiellonian University,Kraków,Poland
,
Pier Luigi Zinzani
Affiliations:
University of Bologna,Bologna,Italy
,
Andre Goy
Affiliations:
John Theurer Cancer Center, Hackensack University Medical Center,Hackensack,United States
,
Mariano Provencio
Affiliations:
University Hospital Puerta De Hierro,Madrid,Spain
,
Zsolt Nagy
Affiliations:
Semmelweis University,Budapest,Hungary
,
Tadeusz Robak
Affiliations:
Medical University of Lodz,Lodz,Poland
,
Kami Maddocks
Affiliations:
The Ohio State University Comprehensive Cancer Center,Columbus,United States
,
Christian Buske
Affiliations:
University of Ulm,Ulm,Germany
,
Roman Korolkiewicz
Affiliations:
MorphoSys AG,Martinsried,Germany
,
Mark Winderlich
Affiliations:
MorphoSys AG,Martinsried,Germany
Kristie Blum
Affiliations:
The Ohio State University Comprehensive Cancer Center,Columbus,United States
EHA Library. Jurczak W. 06/12/15; 100254; E990 Disclosure(s): Jagiellonian University
Dpt of Haematology
Prof. Dr. Wojciech Jurczak
Prof. Dr. Wojciech Jurczak
Contributions
Abstract
Abstract: E990

Type: Eposter Presentation

Background
A number of second-generation monoclonal antibodies (mAbs) that target the antigens CD20 and CD19 have been evaluated across a range of non-Hodgkin's lymphoma (NHL) subtypes combined with chemotherapy, as a single agent, or as maintenance therapy. Although these agents are usually well tolerated and have demonstrated clinical activity in patients (pts) with NHL, there remains a high unmet medical need for new therapies for pts with relapsed or refractory (R-R) B-cell NHL. MOR208 is an Fc-engineered, humanized mAb that targets the B-cell-specific antigen CD19 and which possesses significantly enhanced antibody-dependent cell-mediated toxicity, a key mechanism for tumor cell killing. 

Aims
To evaluate the preliminary efficacy and safety of MOR208 in adult pts with relapsed or refractory NHL.

Methods
This is a non-randomized, open-label, multicenter, two-stage, phase IIa study of MOR208 in pts with R-R NHL previously treated with rituximab who were not candidates for high-dose chemotherapy with stem cell support. Adult pts with diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma (MCL), follicular lymphoma (FL), or other indolent NHL (iNHL), were treated with single-agent MOR208, at an intravenous dose of 12 mg/kg, weekly, over two 28-day cycles. Pts with at least stable disease according to the 2007 International Response Criteria were to continue treatment with MOR208 for another cycle. Pts achieving a complete or partial response (CR or PR) could then receive maintenance MOR208 every two or four weeks, depending on the investigator’s decision, until progression. Overall response rate (ORR = CR + PR) was the primary endpoint.

Results

By 17 November 2014, all pts (N = 89) had been enrolled (DLBCL, n = 35; FL, n = 31; MCL, n = 12; iNHL, n = 11); median age was 67 (range 35–90) years. Of these pts, 88% had stage III–IV disease and the median number of prior therapies was 2 (range 1–4). The mean number of cycles completed was 2.2 (0–3). The investigator-assessed responses across all NHL subtypes are shown in Table 1; the highest ORR was recorded in the DLBCL cohort (26%). Preliminary median duration of response was 7.7 months in the DLBCL group and 2.6 months in the FL group. Grade ≥3 non-hematologic treatment-emergent adverse events (TEAEs) were recorded in 30 pts (34%); disease progression, reported in 10 pts (11%), was most common. Grade ≥3 hematologic TEAEs were recorded in 8 pts (9%); neutropenia, reported in 5 pts (6%), was most common. Infusion-related reactions, reported in 8 pts (9%), were all grade 1–2 except for one case of dyspnea, which was grade 4. There were no treatment-related deaths.

Summary
MOR208 demonstrated encouraging single-agent efficacy with CRs observed in pts with R-R DLBCL, FL, and iNHL. MOR208 is well tolerated without significant infusional toxicity. Protocols are being developed to investigate MOR208 in combination with other agents.

Keyword(s): B cell lymphoma, CD19, Non-Hodgkin's lymphoma, Relapsed lymphoma

Abstract: E990

Type: Eposter Presentation

Background
A number of second-generation monoclonal antibodies (mAbs) that target the antigens CD20 and CD19 have been evaluated across a range of non-Hodgkin's lymphoma (NHL) subtypes combined with chemotherapy, as a single agent, or as maintenance therapy. Although these agents are usually well tolerated and have demonstrated clinical activity in patients (pts) with NHL, there remains a high unmet medical need for new therapies for pts with relapsed or refractory (R-R) B-cell NHL. MOR208 is an Fc-engineered, humanized mAb that targets the B-cell-specific antigen CD19 and which possesses significantly enhanced antibody-dependent cell-mediated toxicity, a key mechanism for tumor cell killing. 

Aims
To evaluate the preliminary efficacy and safety of MOR208 in adult pts with relapsed or refractory NHL.

Methods
This is a non-randomized, open-label, multicenter, two-stage, phase IIa study of MOR208 in pts with R-R NHL previously treated with rituximab who were not candidates for high-dose chemotherapy with stem cell support. Adult pts with diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma (MCL), follicular lymphoma (FL), or other indolent NHL (iNHL), were treated with single-agent MOR208, at an intravenous dose of 12 mg/kg, weekly, over two 28-day cycles. Pts with at least stable disease according to the 2007 International Response Criteria were to continue treatment with MOR208 for another cycle. Pts achieving a complete or partial response (CR or PR) could then receive maintenance MOR208 every two or four weeks, depending on the investigator’s decision, until progression. Overall response rate (ORR = CR + PR) was the primary endpoint.

Results

By 17 November 2014, all pts (N = 89) had been enrolled (DLBCL, n = 35; FL, n = 31; MCL, n = 12; iNHL, n = 11); median age was 67 (range 35–90) years. Of these pts, 88% had stage III–IV disease and the median number of prior therapies was 2 (range 1–4). The mean number of cycles completed was 2.2 (0–3). The investigator-assessed responses across all NHL subtypes are shown in Table 1; the highest ORR was recorded in the DLBCL cohort (26%). Preliminary median duration of response was 7.7 months in the DLBCL group and 2.6 months in the FL group. Grade ≥3 non-hematologic treatment-emergent adverse events (TEAEs) were recorded in 30 pts (34%); disease progression, reported in 10 pts (11%), was most common. Grade ≥3 hematologic TEAEs were recorded in 8 pts (9%); neutropenia, reported in 5 pts (6%), was most common. Infusion-related reactions, reported in 8 pts (9%), were all grade 1–2 except for one case of dyspnea, which was grade 4. There were no treatment-related deaths.

Summary
MOR208 demonstrated encouraging single-agent efficacy with CRs observed in pts with R-R DLBCL, FL, and iNHL. MOR208 is well tolerated without significant infusional toxicity. Protocols are being developed to investigate MOR208 in combination with other agents.

Keyword(s): B cell lymphoma, CD19, Non-Hodgkin's lymphoma, Relapsed lymphoma

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