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3035 Phase I/IIa Study of the Human Anti-CD38 Antibody MOR202 (MOR03087) in Relapsed or Refractory Multiple Myeloma

Myeloma: Therapy, excluding Transplantation
Program: Oral and Poster Abstracts
Session: 653. Myeloma: Therapy, excluding Transplantation: Poster II
Sunday, December 6, 2015, 6:00 PM-8:00 PM
Hall A, Level 2 (Orange County Convention Center)

Marc S Raab, MD, PhD1, Manik Chatterjee, MD2*, Hartmut Goldschmidt, MD3, Hermine Agis, MD4*, Igor W Blau, MD, PhD5*, Hermann Einsele, MD2, Monika Engelhardt, MD6, Barbara Ferstl, MD7*, Martin Gramatzki, MD8, Christoph Röllig, MD9*, Katja C. Weisel10*, Pia Klöpfer, MD11*, Dominika Weinelt, MD11*, Stefan Härtle, PhD11* and Christian Peschel, MD12

1Department of Medicine V, University Hospital Heidelberg, Heidelberg, Germany
2Department of Internal Medicine II, University Hospital of Wuerzburg, Wuerzburg, Germany
3Internal Medicine V, University Clinic Heidelberg, Heidelberg, Germany
4Department of Medicine I, University Hospital of Internal Medicine – AKH Wien, Vienna, Austria
5Department of Internal Medicine III, Charité Campus Benjamin Franklin, Berlin, Germany
6Department of Hematology, Oncology and Stem Cell Transplantation, University of Freiburg Medical Center, Freiburg, Germany
7Department of Internal Medicine 5 - Hematology and Oncology, Friedrich-Alexander-University Erlangen-Nuernberg, Erlangen, Germany
8Department of Medicine, University Hospital Schleswig-Holstein Division of Stem Cell Transplantation and Immunotherapy, Kiel, Germany
9Department of Medicine I, University Hospital Carl Gustav Carus, Dresden, Germany
10Department of Hematology, Oncology, Immunology, Rheumatology and Pulmonology, University Hospital of Tuebingen, Tuebingen, Germany
11MorphoSys AG, Martinsried, Germany
12Department of Internal Medicine III, Technical University of Munich, Munich, Germany

Background: CD38 is a type II transmembrane glycoprotein that is expressed at high levels on multiple myeloma cells. MOR202 is a HuCAL-derived, human, IgG1 anti-CD38 monoclonal antibody showing effective antibody-dependent cell-mediated cytotoxicity (ADCC), antibody-dependent cell-mediated phagocytosis (ADCP), and high activity in preclinical models of multiple myeloma.

Patients and Methods: Here we report interim safety and preliminary efficacy data from this ongoing, multicenter, MOR202 dose-escalation, phase I/IIa study in patients with relapsed or refractory disease who had failed ≥2 prior therapies for multiple myeloma, including an immunomodulatory drug and a proteasome inhibitor. The objectives are to evaluate the safety, maximum tolerated dose (MTD)/recommended dose and preliminary efficacy of MOR202 when administered as monotherapy or in combination with dexamethasone (DEX); pomalidomide (POM) + DEX; and lenalidomide (LEN) + DEX. Patients received MOR202 as a 2-hour intravenous infusion every 2 weeks (q2w; dose levels 0.01–16 mg/kg), 4 mg/kg weekly (q1w) and 4, 8 and 16 mg/kg q1w + DEX. The combination cohorts receiving MOR202 8 mg/kg with LEN + DEX and POM + DEX have been opened, and the 16 mg/kg q1w with LEN + DEX or POM + DEX, as well as confirmation cohorts, are planned.

Results: As of 26 June 2015, 44 patients have been treated; 31 and 13 patients in the q2w and q1w dose levels, respectively. Median age was 69 years (range 44–80); median number of prior therapy lines was 4 (2–11). The MTD has not been reached. The most common treatment-emergent adverse events (TEAEs) at any grade were anemia (15 patients, 34%), fatigue (14 patients, 32%), infusion-related reactions (IRRs) and leukopenia (13 patients, 30% each), lymphopenia and nausea (11 patients, 25% each). Grade ≥3 TEAEs were reported for 28 patients (64%); the most common included lymphopenia (8 patients, 18%), leukopenia (5 patients, 11%) and hypertension (4 patients, 9%). IRRs arose mainly during the first infusion; all were grade 1–2 except for one patient (grade 3); no IRRs occurred in patients receiving MOR202 in combination with DEX. Infections were commonly reported (26 patients, 59%) but in the majority of the cases were not considered to be treatment-related. There have been no treatment-related deaths. Pharmacokinetic (PK) data demonstrated a significant target-mediated drug disposition effect for most patients treated q2w. By contrast, patients treated q1w (4 or 8 mg/kg) showed constant or slightly accumulating MOR202 trough levels, suggesting the potential for full target occupancy at 16 mg/kg. Long-lasting tumor control has already been observed in early monotherapy cohorts, including one partial response and one very good partial response in the weekly cohorts; efficacy analyses are ongoing. First data from the dose escalation of the weekly cohorts with DEX and the combination cohorts with LEN + DEX and POM + DEX will be presented.

Conclusions: At doses up to 16 mg/kg, MOR202 was safe and well tolerated. Encouraging preliminary activity of MOR202 was observed, especially with the weekly regimen. PK data show the potential for full target occupancy in patients receiving MOR202 16 mg/kg q1w. This dosing schedule of MOR202 is currently being tested in combination with DEX, LEN + DEX, and POM + DEX.

Disclosures: Raab: MorphoSys: Research Funding ; Novartis: Consultancy , Research Funding , Speakers Bureau ; Celgene: Consultancy ; BMS: Consultancy . Goldschmidt: Chugai: Honoraria , Research Funding , Speakers Bureau ; Onyx: Consultancy , Honoraria , Membership on an entity’s Board of Directors or advisory committees , Speakers Bureau ; Millenium: Honoraria , Research Funding , Speakers Bureau ; Janssen-Cilag: Consultancy , Honoraria , Membership on an entity’s Board of Directors or advisory committees , Research Funding , Speakers Bureau ; Bristol-Myers Squibb: Consultancy , Membership on an entity’s Board of Directors or advisory committees , Research Funding ; Novartis: Consultancy , Honoraria , Membership on an entity’s Board of Directors or advisory committees , Research Funding , Speakers Bureau ; Takeda: Consultancy , Membership on an entity’s Board of Directors or advisory committees ; Amgen: Consultancy , Membership on an entity’s Board of Directors or advisory committees ; Celgene: Consultancy , Honoraria , Membership on an entity’s Board of Directors or advisory committees , Research Funding , Speakers Bureau . Einsele: Janssen: Consultancy , Honoraria , Research Funding , Speakers Bureau ; Novartis: Consultancy , Honoraria , Research Funding , Speakers Bureau ; Amgen/Onyx: Consultancy , Honoraria , Research Funding , Speakers Bureau ; Celgene: Consultancy , Honoraria , Research Funding , Speakers Bureau . Ferstl: Bristol-Myers Squibb: Other: Advisory board ; Novartis: Other: Case report presentation . Weisel: Celgene: Consultancy , Honoraria , Other: Travel Support , Research Funding ; Amgen: Consultancy , Honoraria , Other: Travel Support ; Novartis: Other: Travel Support ; Janssen Pharmaceuticals: Consultancy , Honoraria , Other: Travel Support , Research Funding ; BMS: Consultancy , Honoraria , Other: Travel Support ; Onyx: Consultancy , Honoraria ; Noxxon: Consultancy . Klöpfer: MorphoSys: Employment . Weinelt: MorphoSys: Employment . Härtle: MorphoSys: Employment .

*signifies non-member of ASH