ROME—Combination therapy incorporating a novel monoclonal antibody (mAb) can provide “encouraging, long-lasting tumor control” in heavily pretreated patients with relapsed/refractory multiple myeloma (MM), according to investigators.
The mAb, MOR202, was also considered to be well-tolerated in this ongoing phase 1/2a study.
Early results from this study were presented at the 15th International Myeloma Workshop (poster #156). The study was sponsored by MorphoSys AG, makers of MOR202. The poster is available on the company’s website.
MOR202 is a HuCAL-derived mAb directed against CD38. In the phase 1/2a study, 50 MM patients have received the drug thus far.
At baseline, the patients’ median age was 67. They had received a median of 4 prior therapies, including bortezomib (98%), lenalidomide (92%), melphalan (92%), cyclophosphamide (76%), doxorubicin (60%), thalidomide (32%), pomalidomide (14%), carfilzomib (6%), elotuzumab (4%), and panobinostat (4%). Seventy-six percent had received a stem cell transplant.
The study consists of several parts and dosing cohorts in which the investigators are assessing MOR202 alone or in combination with other agents.
Treatment in Part A consists of a 2-hour intravenous infusion of MOR202 once every 2 weeks at several different doses: 0.01 mg/kg , 0.04 mg/kg, 0.15 mg/kg, 0.5 mg/kg, 1.5 mg/kg, 4.0 mg/kg, 8.0 mg/kg, or 16.0 mg/kg.
Part B is a 2-hour intravenous infusion of MOR202 once a week at 4 mg/kg, 8 mg/kg, or 16 mg/kg.
Part C is dexamethasone plus MOR202 once a week at 4 mg/kg, 8 mg/kg, or 16 mg/kg.
Part D is pomalidomide, dexamethasone, and MOR202 once a week at 8 mg/kg or 16 mg/kg.
Part E is lenalidomide, dexamethasone, and MOR202 once a week at 8 mg/kg or 16 mg/kg.
In the confirmatory cohorts, patients receive MOR202 with or without dexamethasone once a week or once every 2 weeks, MOR202 with pomalidomide and dexamethasone once a week, or MOR202 with lenalidomide and dexamethasone once a week.
Of the 50 patients treated thus far, 27 were evaluable for efficacy. One patient achieved a very good partial response, 2 had a partial response, and 2 had a minor response. Eleven patients had stable disease, and 11 progressed.
The very good partial response occurred in a patient receiving weekly MOR202 at 4 mg/kg plus dexamethasone.
One partial response occurred in a patient receiving weekly MOR202 at 8 mg/kg plus dexamethasone. The other occurred in a patient receiving weekly MOR202 at 8 mg/kg plus dexamethasone and pomalidomide.
One minor response occurred in a patient receiving weekly MOR202 at 8 mg/kg plus dexamethasone and lenalidomide. The other occurred in a patient receiving weekly MOR202 at 16 mg/kg plus dexamethasone.
“[T]he preliminary efficacy seen so far with MOR202 as single agent and in combinations is promising,” said investigator Marc-Steffen Raab, MD, of Heidelberg University Hospital and the German Cancer Research Center DKFZ in Heidelberg, Germany.
All 50 patients were evaluable for safety. Ninety-eight percent experienced an adverse event (AE), 66% of which were grade 3 or higher.
The most frequent AEs (overall and grade 3 or higher) were anemia (34%, 6%), leukopenia (30%, 10%), neutropenia (20%, 10%), thrombocytopenia (18%, 8%), fatigue (30%, 0%), nausea (22%, 0%), diarrhea (20%, 0%), and headache (16%, 0%).
Thirty-six percent of patients discontinued MOR202 due to treatment-emergent AEs. However, only 6% (n=3) of these AEs were considered possibly related to MOR202.
Infusion-related reactions occurred in 15 patients (30%). One of these patients received dexamethasone as well and experienced an infusion-related reaction (grade 1).
In the absence of dexamethasone, nearly all infusion reactions were grade 1-2. The exception was 1 patient with a grade 3 reaction that was mainly limited to the first infusion.
The maximum tolerated dose of MOR202 has not been reached.
“Considering the low rate of infusion reactions, even in cohorts without dexamethasone, the short infusion time, and other aspects, MOR202 may turn out to be an excellent choice in terms of safety and tolerability,” Dr Raab concluded.