MorphoSys, Xencor announce final results from MOR208 Phase 1/2a trial in patients with CLL/SLL

MorphoSys AG (FSE: MOR; Prime Standard Segment, TecDAX, OTC: MPSYY) and Xencor Inc. (NASDAQ: XNCR) today announced the publication of final results of a Phase 1/2a trial evaluating MOR208 (formerly XmAb5574) in patients with relapsed or refractory chronic lymphocytic leukemia/small lymphocytic leukemia (CLL/SLL). MOR208 is a potent anti-CD19 antibody with a proprietary modification to the Fc portion that is being developed to treat B-cell malignancies. MOR208 was in-licensed by MorphoSys from Xencor in 2010.

The results demonstrate that the drug was well tolerated and achieved durable responses in a high risk and poor prognosis patient population with significant progression-free survival achieved:

• At recommended dose 12 patients (75%) had a partial response by physical exam criteria (IWCLL1996) and 6 patients (37.5%) had a partial response using additional CT criteria (IWCLL2008)
• Blood disease cleared in most patients, with median reduction in absolute lymphocyte count from baseline of 90.8%
• Progression-free survival of up to 60 weeks for patients in extended treatment arm

"The data presented by the Ohio State University and our collaboration partner Xencor complement the clinical results we will present tomorrow at ASH for MOR208 in NHL. In the meantime, phase 2 clinical evaluation of MOR208 in CLL in combination with lenalidomide as well as in NHL and ALL is ongoing. Taken together the MOR208 program has advanced significantly in 2014 and the clinical evidence supporting this program is stronger than ever," commented Dr. Arndt Schottelius, Chief Development Officer of MorphoSys AG.

"The activity observed with MOR208 in this difficult to treat population, particularly the durability and tolerability, position the program well for further development," said Bassil Dahiyat, President and CEO of Xencor. "Further, these data demonstrate the high anti-tumor activity that our cytotoxic XmAb® Fc domain creates in antibodies."

The Phase 1/2a trial was designed to assess the drug's safety, tolerability, pharmacokinetic profile and preliminary anti-tumor activity. MOR208 was administered as an intravenous infusion on days 1, 4, 8, 15, and 22 of cycle 1, and on days 1, 8, 15, and 22 of cycle 2. Dose levels tested ranged from 0.3 to 12 mg/kg with an expansion to a total of 16 patients at the highest dose.

In total, 27 patients were enrolled, with a median age of 66 years. The patients were generally high risk: 14 patients had high-risk disease by the Rai staging system; 18 patients had chromosome abnormalities – 10 patients with del(17p13.1) and 8 with del(11q22.3); 24 patients had IgVH unmutated disease. All of these factors lead to a poor prognosis in clinical practice. Patients had a median of 4 prior therapies, with a range of 1 to up to 13.

MOR208 was generally well tolerated with no maximum-tolerated dose identified. The most common adverse events were infusion reactions, increased aspartate transaminase (AST), increased alanine aminotransferase (ALT), neutropenia, thrombocytopenia, fever, chills, and peripheral neuropathy. Infusion reactions occurred in 67% of patients, however, all were grade 1 or 2, and no reactions were seen following the first infusion.

On the basis of physical exam and laboratory studies, 18 patients (66.7%) achieved a partial response (PR), and the remaining 9 patients (33.3%) achieved stable disease (SD). Adding CT criteria, 8 patients (29.6%) achieved a PR with an additional 16 patients (59.3%) achieving SD. Two patients had progressive disease by CT criteria. Evaluating only the 16 patients at the 12 mg/kg dose level, which is the recommended phase 2 dose, 12 patients (75%) had a PR by physical exam criteria and 6 patients (37.5%) had a PR by CT criteria, two of these patients achieving the PR during the maintenance phase. Blood disease cleared in most patients, with a median reduction in absolute lymphocyte count from baseline of 90.8% and a decrease in CLL cell count. Median progression-free survival (PFS) for all patients was 199 days. For the 8 patients on the extended treatment cohort, PFS was 420 days.

"While not the primary endpoint of this trial, efficacy with this antibody is encouraging, with 67% of patients achieving a PR by clinical criteria and 30% using IWCLL 2008 criteria," commented Jennifer A. Woyach, Assistant Professor at the Ohio State University's Comprehensive Cancer Center and principle investigator of the trial. "These response rates are impressive for a single agent antibody and compare favorably with results for rituximab given on a weekly schedule as well as ofatumumab and obinutuzumab in the relapsed setting."