Emergent BioSolutions Inc., a specialty pharmaceutical company, has reported preliminary results from a phase Ib single-arm, open-label study evaluating the safety and efficacy of otlertuzumab (TRU-016) in combination with rituximab in people with previously untreated chronic lymphocytic leukaemia (CLL) (Study 16009). Data from the first cohort to have completed enrollment, was presented during the American Society of Hematology annual meeting, which showed the combination was active and well tolerated.

Otlertuzumab is a humanized anti-CD37 monospecific protein therapeutic, built on Emergent’s ADAPTIR (modular protein technology) platform, that targets the CD37 signaling pathway involved in B-cell malignancies such as CLL, non-Hodgkin’s lymphoma (NHL), diffuse large B-cell lymphoma (DLBCL) and other cancers of the blood.

“Emergent is pleased with the data from Cohort 1 of this phase Ib study that show the safety and activity of otlertuzumab in combination with rituximab,” said Scott C Stromatt, MD, senior vice president and chief medical officer, Emergent BioSolutions. “The ability to possibly combine therapies like otlertuzumab with existing approved treatments or even future therapies could provide expanded treatment options to people with CLL.”

The phase Ib study, initiated in October 2012, was designed to evaluate the efficacy and safety of the combination of otlertuzumab and rituximab in patients with a diagnosis of CLL. In Cohort 1, twenty four previously untreated patients received otlertuzumab (20 mg/kg) followed by rituximab (375 mg/m2 the first dose then 500 mg/m2 for subsequent doses).

Overall response rate (ORR) by 2008 International Workshop on CLL (IWCLL) Response Criteria was the primary efficacy endpoint of the study. For the 20 patients who have necessary CT scans and have completed treatment, the ORR per IWCLL criteria was 50 percent. Complete response (CR), one of the secondary endpoints, was five per cent. One patient was minimal residual disease (MRD) negative on examination of bone marrow by five color flow cytometry. The response by investigator assessment using National Cancer Institute criteria was an ORR of 96 per cent and CR of 33 per cent.

Otlertuzumab was well tolerated in Cohort 1.54 per cent of patients experienced infusion reactions, most of which were grade 1 or 2 with only two grade 3 reactions. None of the infusion reactions resulted in study drug discontinuation.

In April 2013, Emergent announced an expanded protocol to include two additional study cohorts to examine the combination of otlertuzumab and rituximab in relapsed CLL patients (Cohort 2) and to evaluate a lower dose of otlertuzumab in combination with rituximab in previously untreated patients (Cohort 3). Treatment and follow up are ongoing for patients in these expanded cohorts to determine response. Follow up of patients in all 3 cohorts will be continued in order to assess progression free survival.

Otlertuzumab is a CD37-specific therapeutic protein in development for the treatment of B-cell malignancies such as CLL that was built on the ADAPTIR™ (modular protein technology) platform. CD37 is a tetraspanin protein expressed on the surface of normal and transformed B cells and demonstrates death signaling via SHP1.

ADAPTIR monospecific proteins are single chain polypeptides that comprise three components: a binding domain (VL and VH), a hinge domain, and an effector domain (huFc). They have a differentiated structure from monoclonal antibodies and can generate a unique signaling response. In addition, ADAPTIR proteins may mediate complement dependent cytotoxicity and Fc dependent cytotoxicity, similar to monoclonal antibodies.

Emergent BioSolutions is a specialty pharmaceutical company seeking to protect and enhance life by offering specialized products to healthcare providers and governments to address medical needs and emerging health threats.