A phase I/IIa study of the human anti-CD38 antibody MOR202 (MOR03087) in relapsed or refractory multiple myeloma (rrMM).

8574 Background: MOR202 is a HuCAL-derived fully human IgG1 anti-CD38 antibody, with high efficacy in preclinical models of MM. Methods: This is an open-label, dose-escalation study (3 + 3 design) to evaluate the safety and preliminary efficacy of MOR202 in adult patients (pts) with rrMM. We present the data of pts previously treated with ≥ 2 prior therapies including an immunomodulatory drug and a proteasome inhibitor. Pts received 2-hour IV MOR202 every 2 weeks (q2w) (8 dose levels DLs from 0.01–16 mg/kg) without dexamethasone (DEX), or 4 or 8 mg/kg (DLs 6 and 7), weekly (q1w) +/- DEX. MOR202 16 mg/kg (DL 8) q1w +/- DEX and combination cohorts with lenalidomide (LEN)/pomalidomide (POM) + DEX are planned, as well as confirmation cohorts. Results: As of December 31st 2014, 38 pts had been treated; 29 and 9 pts in the q2w and q1w DLs, respectively. Median age was 70 (44–80) yrs. The median number of prior treatment lines was 4 (2–10) for all pts. 36 pts (94.7%) developed AEs. The most frequently reported AEs ( > 10%) of any grade were anemia (31.6%), fatigue (28.9%), WBC decreased (21.1%), lymphocyte count decreased (LCD) (21.1%), diarrhea (21.1%), nasopharyngitis (18.4%) and leukopenia (13.2%). Grade ≥ 3 hematologic AEs were LCD (15.8%), WBC decreased (7.9%), leukopenia (5.3%), thrombocytopenia (2.6%) and lymphopenia (2.6%). Infusion-related reactions occurred in 13 pts (34%) receiving MOR202 without DEX, mainly during the first infusion. All were grade 1-2 except for 1 pt grade 3. There have been no treatment-related deaths. PK data demonstrate a significant target-mediated drug disposition effect for most pts treated q2w. In 4/6 pts in the q1w 4 mg/kg cohort MOR202 trough levels show the start of target saturation. Only 1 pt (MOR202 0.15 mg/kg q2w) generated a transient anti-drug antibody response to MOR202. Conclusions: The MTD has not been reached. MOR202 is safe and well tolerated. PK data show the potential for full target occupancy in the majority of pts receiving 8 and 16 mg/kg q1w. These latter DLs of MOR202 will be tested as monotherapy or in combination with DEX, LEN + DEX and POM + DEX in the upcoming cohorts. Efficacy analyses are ongoing. Clinical trial information: NCT01421186.