Safety and Tolerability of MOR202 in Relapsed/Refractory Myeloma Patients

A recent phase I/IIa study evaluated the safety and efficacy of MOR202, a human monoclonal anti-CD38 antibody, in adult patients with relapsed/refractory multiple myeloma (MM), and found that the novel drug was safe and well tolerated in this heavily pretreated cohort.

These results, presented by Marc S. Raab, MD, from the University Hospital Heidelberg in Germany, at the 2015 European Hematology Association Congress, confirmed the high in vitro and in vivo efficacy that was demonstrated in previous preclinical studies.

Dr. Raab and colleagues conducted this open-label, dose-escalating study to determine the maximum tolerated dose (MTD) and/or recommended dose/schedule of MOR202. The authors examined the following doses and schedules:

  • as a single agent (MOR202; biweekly dosing at 0.01 mg/kg to 16 mg/kg)
  • in combination with dexamethasone (MOR202/DEX; MOR202 once-weekly at 4 mg/kg or 8 mg/kg)
  • in combination with pomalidomide/dexamethasone (MOR202/POM/DEX)
  • in combination with lenalidomide/dexamethasone (MOR202/LEN/DEX)

The primary outcomes measured were MTD, safety (defined as incidence and severity of adverse events [AEs]), and immunogenicity of MOR202.

All patients included in the study had been previously treated with more than two prior therapies, including an immunomodulatory drug and a proteasome inhibitor. Patients were excluded from the study if they had primary refractory MM, solitary plasmacytoma or plasma cell leukemia, or a previous allogenic hematopoietic cell transplant.

The study is ongoing, and as of April 13, 2015, 42 patients had been treated. The median age was 69.5 years (range = 44-80 years), and the median number of prior therapies was four (range = 2-11 therapies) for all patients. A total of 36 patients (94.7%) developed treatment-related AEs.

The most commonly reported hematologic AEs (≥10%) of any grade among all patients were:

  • Anemia (33.3%; grade ≥3 = 2.4%)
  • Decreased lymphocyte count (19.0%; grade ≥3 = 14.3%)
  • Decreased white blood cell count (19.0%; grade ≥3 = 7.1%)
  • Leukopenia (14.3%; grade ≥3 = 4.8%)
  • Decreased neutrophil count (11.9%; grade ≥3 = 2.4%)
  • Thrombocytopenia (11.9%; grade ≥3 = 4.8%)

The most commonly reported non-hematologic AEs (≥15%) were:

  • Fatigue (33.3%)
  • Nausea (26.2%)
  • Diarrhea (19.0%)
  • Headache (16.7%)
  • Nasopharyngitis (16.7%)
  • Pyrexia (16.7%)

Infusion-related AEs occurred in 31 percent of patients (n=13): only in patients receiving MOR202 as monotherapy and mainly during the first infusion. All infusion-related AEs were grade 1 or 2, although one patient experienced a grade 3 reaction.

No treatment-related deaths were reported.

“Pharmacokinetic data show the potential for full target occupancy in the majority of patients receiving 8 mg/kg and 16 mg/kg weekly,” Dr. Raab and co-authors observed. In four of six patients treated once-weekly with MOR202 4 mg/kg, MOR202 trough levels showed the beginning of target saturation. Just one patient treated with MOR202 0.15 mg/kg biweekly generated a transient anti-drug antibody response to MOR202.

At the time of the presentation, “the maximum tolerated dose has not been reached, [suggesting that] MOR202 is safe and well tolerated,” they concluded. “These [8 mg/kg and 16 mg/kg once-weekly] dose levels of MOR202 will be tested as monotherapy or in combination with dexamethasone, lenalidomide plus dexamethasone, and pomalidomide plus dexamethasone, in the upcoming cohorts.”

Future studies are likely to compare MOR202 with other anti-CD38 monoclonal antibodies, as well.


Reference

Raab MS, Chatterjee M, Goldschmidt H, et al. A phase I/IIA study of the human anti-CD38 antibody MOR202 (MOR03087) in relapsed or refractory multiple myeloma. Abstract #S789. Presented at the 2015 European Hematology Association; June 14, 2015; Vienna, Austria.

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