MorphoSys and Xencor Publish Final Results from Phase 1/2a Trial of MOR208 (XmAb5574) in CLL/SLL at ASH Annual Meeting - Seite 2

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 favourably with results for rituximab given on a weekly schedule as well as ofatumumab and obinutuzumab in the relapsed setting."