A PHASE I/IIA STUDY OF THE HUMAN ANTI-CD38 ANTIBODY MOR202 (MOR03087) IN RELAPSED OR REFRACTORY MULTIPLE MYELOMA
(Abstract release date: 05/21/15)
EHA Library. Raab M. 06/14/15; 103053; S789
Disclosure(s): University Hospital Heidelberg
Dr. Marc S. Raab
Contributions
Contributions
Abstract
Abstract: S789
Type: Oral Presentation
Presentation during EHA20: From 14.06.2015 09:00 to 14.06.2015 09:15
Location: Room A2+3
Background
MOR202 is a HuCAL-derived fully human immunoglobulin G1 (IgG1) anti-CD38 antibody, with high efficacy in preclinical models of multiple myeloma.
Aims
To evaluate the safety and preliminary efficacy of MOR202 in adult patients with relapsed or refractory multiple myeloma.
Methods
This is an open-label dose-escalation study (3 + 3 design). The data of patients previously treated with ≥2 prior therapies, including an immunomodulatory drug and a proteasome inhibitor, are presented. Patients received 2-hour intravenous MOR202 every 2 weeks (q2w; 8 dose levels from 0.01–16 mg/kg) without dexamethasone, or 4 or 8 mg/kg (dose levels 6 and 7) weekly (q1w) +/- dexamethasone. MOR202 16 mg/kg (dose level 8) q1w +/- dexamethasone, and combination cohorts with lenalidomide + dexamethasone and pomalidomide + dexamethasone, are planned, as well as confirmation cohorts.
Results
As of December 31 2014, 38 patients had been treated; 29 and 9 patients in the q2w and q1w dose levels, respectively. Median age was 70 (44–80) years. The median number of prior treatment lines was 4 (2–10) for all patients. A total of 36 patients (94.7%) developed adverse events. The most frequently reported adverse events (>10%) of any grade were anemia (31.6%), fatigue (28.9%), white blood cell count decreased (21.1%), lymphocyte count decreased (21.1%), diarrhea (21.1%), nasopharyngitis (18.4%), and leukopenia (13.2%). Grade ≥3 hematologic adverse events were lymphocyte count decreased (15.8%), white blood cell count decreased (7.9%), leukopenia (5.3%), thrombocytopenia (2.6%), and lymphopenia (2.6%). Infusion-related reactions occurred in 13 patients (34%) receiving MOR202 without dexamethasone, mainly during the first infusion. All were grade 1–2 except for 1 patient (grade 3). There have been no treatment-related deaths. Pharmacokinetic data demonstrate a significant target-mediated drug disposition effect for most patients treated q2w. In 4 out of 6 patients in the q1w 4 mg/kg cohort, MOR202 trough levels show the start of target saturation. Only 1 patient (MOR202 0.15 mg/kg q2w) generated a transient anti-drug antibody response to MOR202.
Summary
The maximum tolerated dose has not been reached. MOR202 is safe and well tolerated. Pharmacokinetic data show the potential for full target occupancy in the majority of patients receiving 8 and 16 mg/kg q1w. These latter dose levels of MOR202 will be tested as monotherapy or in combination with dexamethasone, lenalidomide + dexamethasone, and pomalidomide + dexamethasone, in the upcoming cohorts. Efficacy analyses are ongoing.
Keyword(s): Antibody, CD38, Dose escalation, Multiple myeloma
Session topic: Multiple myeloma: Clinical studies 3
Type: Oral Presentation
Presentation during EHA20: From 14.06.2015 09:00 to 14.06.2015 09:15
Location: Room A2+3
Background
MOR202 is a HuCAL-derived fully human immunoglobulin G1 (IgG1) anti-CD38 antibody, with high efficacy in preclinical models of multiple myeloma.
Aims
To evaluate the safety and preliminary efficacy of MOR202 in adult patients with relapsed or refractory multiple myeloma.
Methods
This is an open-label dose-escalation study (3 + 3 design). The data of patients previously treated with ≥2 prior therapies, including an immunomodulatory drug and a proteasome inhibitor, are presented. Patients received 2-hour intravenous MOR202 every 2 weeks (q2w; 8 dose levels from 0.01–16 mg/kg) without dexamethasone, or 4 or 8 mg/kg (dose levels 6 and 7) weekly (q1w) +/- dexamethasone. MOR202 16 mg/kg (dose level 8) q1w +/- dexamethasone, and combination cohorts with lenalidomide + dexamethasone and pomalidomide + dexamethasone, are planned, as well as confirmation cohorts.
Results
As of December 31 2014, 38 patients had been treated; 29 and 9 patients in the q2w and q1w dose levels, respectively. Median age was 70 (44–80) years. The median number of prior treatment lines was 4 (2–10) for all patients. A total of 36 patients (94.7%) developed adverse events. The most frequently reported adverse events (>10%) of any grade were anemia (31.6%), fatigue (28.9%), white blood cell count decreased (21.1%), lymphocyte count decreased (21.1%), diarrhea (21.1%), nasopharyngitis (18.4%), and leukopenia (13.2%). Grade ≥3 hematologic adverse events were lymphocyte count decreased (15.8%), white blood cell count decreased (7.9%), leukopenia (5.3%), thrombocytopenia (2.6%), and lymphopenia (2.6%). Infusion-related reactions occurred in 13 patients (34%) receiving MOR202 without dexamethasone, mainly during the first infusion. All were grade 1–2 except for 1 patient (grade 3). There have been no treatment-related deaths. Pharmacokinetic data demonstrate a significant target-mediated drug disposition effect for most patients treated q2w. In 4 out of 6 patients in the q1w 4 mg/kg cohort, MOR202 trough levels show the start of target saturation. Only 1 patient (MOR202 0.15 mg/kg q2w) generated a transient anti-drug antibody response to MOR202.
Summary
The maximum tolerated dose has not been reached. MOR202 is safe and well tolerated. Pharmacokinetic data show the potential for full target occupancy in the majority of patients receiving 8 and 16 mg/kg q1w. These latter dose levels of MOR202 will be tested as monotherapy or in combination with dexamethasone, lenalidomide + dexamethasone, and pomalidomide + dexamethasone, in the upcoming cohorts. Efficacy analyses are ongoing.
Keyword(s): Antibody, CD38, Dose escalation, Multiple myeloma
Session topic: Multiple myeloma: Clinical studies 3
Abstract: S789
Type: Oral Presentation
Presentation during EHA20: From 14.06.2015 09:00 to 14.06.2015 09:15
Location: Room A2+3
Background
MOR202 is a HuCAL-derived fully human immunoglobulin G1 (IgG1) anti-CD38 antibody, with high efficacy in preclinical models of multiple myeloma.
Aims
To evaluate the safety and preliminary efficacy of MOR202 in adult patients with relapsed or refractory multiple myeloma.
Methods
This is an open-label dose-escalation study (3 + 3 design). The data of patients previously treated with ≥2 prior therapies, including an immunomodulatory drug and a proteasome inhibitor, are presented. Patients received 2-hour intravenous MOR202 every 2 weeks (q2w; 8 dose levels from 0.01–16 mg/kg) without dexamethasone, or 4 or 8 mg/kg (dose levels 6 and 7) weekly (q1w) +/- dexamethasone. MOR202 16 mg/kg (dose level 8) q1w +/- dexamethasone, and combination cohorts with lenalidomide + dexamethasone and pomalidomide + dexamethasone, are planned, as well as confirmation cohorts.
Results
As of December 31 2014, 38 patients had been treated; 29 and 9 patients in the q2w and q1w dose levels, respectively. Median age was 70 (44–80) years. The median number of prior treatment lines was 4 (2–10) for all patients. A total of 36 patients (94.7%) developed adverse events. The most frequently reported adverse events (>10%) of any grade were anemia (31.6%), fatigue (28.9%), white blood cell count decreased (21.1%), lymphocyte count decreased (21.1%), diarrhea (21.1%), nasopharyngitis (18.4%), and leukopenia (13.2%). Grade ≥3 hematologic adverse events were lymphocyte count decreased (15.8%), white blood cell count decreased (7.9%), leukopenia (5.3%), thrombocytopenia (2.6%), and lymphopenia (2.6%). Infusion-related reactions occurred in 13 patients (34%) receiving MOR202 without dexamethasone, mainly during the first infusion. All were grade 1–2 except for 1 patient (grade 3). There have been no treatment-related deaths. Pharmacokinetic data demonstrate a significant target-mediated drug disposition effect for most patients treated q2w. In 4 out of 6 patients in the q1w 4 mg/kg cohort, MOR202 trough levels show the start of target saturation. Only 1 patient (MOR202 0.15 mg/kg q2w) generated a transient anti-drug antibody response to MOR202.
Summary
The maximum tolerated dose has not been reached. MOR202 is safe and well tolerated. Pharmacokinetic data show the potential for full target occupancy in the majority of patients receiving 8 and 16 mg/kg q1w. These latter dose levels of MOR202 will be tested as monotherapy or in combination with dexamethasone, lenalidomide + dexamethasone, and pomalidomide + dexamethasone, in the upcoming cohorts. Efficacy analyses are ongoing.
Keyword(s): Antibody, CD38, Dose escalation, Multiple myeloma
Session topic: Multiple myeloma: Clinical studies 3
Type: Oral Presentation
Presentation during EHA20: From 14.06.2015 09:00 to 14.06.2015 09:15
Location: Room A2+3
Background
MOR202 is a HuCAL-derived fully human immunoglobulin G1 (IgG1) anti-CD38 antibody, with high efficacy in preclinical models of multiple myeloma.
Aims
To evaluate the safety and preliminary efficacy of MOR202 in adult patients with relapsed or refractory multiple myeloma.
Methods
This is an open-label dose-escalation study (3 + 3 design). The data of patients previously treated with ≥2 prior therapies, including an immunomodulatory drug and a proteasome inhibitor, are presented. Patients received 2-hour intravenous MOR202 every 2 weeks (q2w; 8 dose levels from 0.01–16 mg/kg) without dexamethasone, or 4 or 8 mg/kg (dose levels 6 and 7) weekly (q1w) +/- dexamethasone. MOR202 16 mg/kg (dose level 8) q1w +/- dexamethasone, and combination cohorts with lenalidomide + dexamethasone and pomalidomide + dexamethasone, are planned, as well as confirmation cohorts.
Results
As of December 31 2014, 38 patients had been treated; 29 and 9 patients in the q2w and q1w dose levels, respectively. Median age was 70 (44–80) years. The median number of prior treatment lines was 4 (2–10) for all patients. A total of 36 patients (94.7%) developed adverse events. The most frequently reported adverse events (>10%) of any grade were anemia (31.6%), fatigue (28.9%), white blood cell count decreased (21.1%), lymphocyte count decreased (21.1%), diarrhea (21.1%), nasopharyngitis (18.4%), and leukopenia (13.2%). Grade ≥3 hematologic adverse events were lymphocyte count decreased (15.8%), white blood cell count decreased (7.9%), leukopenia (5.3%), thrombocytopenia (2.6%), and lymphopenia (2.6%). Infusion-related reactions occurred in 13 patients (34%) receiving MOR202 without dexamethasone, mainly during the first infusion. All were grade 1–2 except for 1 patient (grade 3). There have been no treatment-related deaths. Pharmacokinetic data demonstrate a significant target-mediated drug disposition effect for most patients treated q2w. In 4 out of 6 patients in the q1w 4 mg/kg cohort, MOR202 trough levels show the start of target saturation. Only 1 patient (MOR202 0.15 mg/kg q2w) generated a transient anti-drug antibody response to MOR202.
Summary
The maximum tolerated dose has not been reached. MOR202 is safe and well tolerated. Pharmacokinetic data show the potential for full target occupancy in the majority of patients receiving 8 and 16 mg/kg q1w. These latter dose levels of MOR202 will be tested as monotherapy or in combination with dexamethasone, lenalidomide + dexamethasone, and pomalidomide + dexamethasone, in the upcoming cohorts. Efficacy analyses are ongoing.
Keyword(s): Antibody, CD38, Dose escalation, Multiple myeloma
Session topic: Multiple myeloma: Clinical studies 3
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