Date: 2014-12-07
Type of information: Results
phase: 1-2a
Announcement: results
Company: Morphosys (Germany) Xencor (USA - CA)
Product: MOR208 (Xmab5574)
Action
mechanism: monoclonal antibody. MOR208 (formerly XmAb®5574) is a potent anti-CD19 antibody with a proprietary modification to the Fc portion, that is being developedto treat B-cell malignancies. In June 2010, MorphoSys AG and Xencor signed a worldwide exclusive license and collaboration agreement. The agreement provided MorphoSys with an exclusive worldwide license to MOR208 for the treatment of cancer and other indications. Using Xencor's XmAb Fc enhancement technology, MOR208 has been engineered to possess significantly enhanced antibody-dependent cell-mediated cytotoxicity (ADCC), thus improving a key mechanism for tumor cell killing and offering potential for enhanced efficacy compared to traditional antibodies for the treatment of cancer. MorphoSys will be solely responsible for further clinical development after successful completion of the phase 1 clinical trial. MorphoSys plans to initiate additional clinical trials for MOR208 in non-Hodgkin's lymphoma (NHL) and acute lymphoblastic leukemia (ALL) in the fourth quarter of 2012.
Disease: relapsed or refractory chronic lymphocytic leukemia/small lymphocytic leukemia (CLL/SLL)
Therapeutic area: Cancer - Oncology
Country:
Trial
details: 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.
Clinical responses were assessed according to International Working Group on CLL (IWCLL) 2008 and 1996 Guidelines. Eight patients qualified for the extended treatment group and received up to four additional treatment cycles with MOR208 including prolonged additional disease response assessments.
Latest
news: * On December 7, 2014, MorphoSys and Xencor 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). 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 (IWCLL 1996) and 6 patients (37.5%) had a partial response using additional CT criteria (IWCLL 2008)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 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. A research paper presenting and discussing the results in CLL/SLL was recently published in the online issue of the peer-reviewed medical journal Blood.* On October 7, 2013, MorphoSys and Xencor have announced completion of the phase 1/2a clinical trial evaluating MOR208 (formerly XmAb®5574) in patients with relapsed or refractory chronic lymphocytic leukemia (CLL/SLL). Safety and objective response data following the protocol defined 8-week treatment period was presented at the American Society of Hematology Annual Meeting in December 2012 (See below). Due to signs of activity of MOR208 in this difficult to treat patient population, the study protocol was amended to allow those patients in the highest dose group benefitting from the treatment to enter a prolonged treatment group. The final study results including the extended treatment arm showed an overall response rate of 29.6% (according to IWCLL 2008 criteria) based on the safety population of the trial (n=27) - up from the previously reported 14.8%. A detailed analysis of the study results will be published in a peer-reviewed scientific journal.* On November 6, 2012, MorphoSys and Xencor have announced the online publication of first clinical data on the anti-CD19 antibody MOR208 (MOR00208/XmAb5574) in the American Society of Hematology Annual Meeting Abstracts issue of the peer-reviewed medical journal Blood . MOR208 showed encouraging signs of preliminary anti-tumor activity and an acceptable safety and tolerability profile in patients with high-risk, heavily pretreated chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). The data support further development of the compound. Based on these results, MorphoSys plans to commence phase 2 studies of MOR208 in B-cell malignancies in the near future. Among the 27 evaluable patients, three partial responses were observed at the 6, 9, and 12 mg/kg dose levels. In addition, 22 patients experienced stable disease and only two patients progressed at the 8 week evaluation point. Overall response rate by IWCLL 2008 criteria was 11% which utilizes more rigorous CT scan reduction of internal lymph nodes not previously required in older historic studies. Using IWCLL 1996 response criteria resulted in a response rate of 42%. The most common adverse events were mild to moderate infusion reactions usually with the first dose. Treatment-related adverse events classified as grade 3 or higher occurred in 5 out of 27 patients. Only one dose-limiting toxicity was observed in 16 patients treated at the 12 mg/kg dose level and the trial protocol was amended to include a period of extended dosing with a total of 8 patients at this dose. Final phase 1/2a data will be presented at the 2012 American Society of Hematology (ASH) annual meeting from December 8-11, 2012 in Atlanta.* On May 22, 2012, MorphoSys and Xencor have announced the successful completion of patient enrollment in the phase 1 clinical trial evaluating MOR208. A total of 30 patients with relapsed or refractory chronic lymphocytic leukemia (CLL/SLL) have been randomized in the open-label, multi-dose, single-arm, dose-escalation study. No dose-limiting toxicity was observed and the trial protocol was amended to include a period of extended dosing for patients responding to treatment. The phase 1 trial was designed to assess the drug's safety, tolerability, pharmacokinetic profile and preliminary anti-tumor activity. Data from the trial will become available in Q4 2012. In total, MorphoSys currently has four proprietary clinical programs ongoing, including MOR208, MOR103, a fully human HuCAL antibody directed against GM-CSF (granulocyte macrophage-colony stimulating factor), in RA and MS, as well as MOR202, a HuCAL antibody targeting CD38, in multiple myeloma. In June 2010, MorphoSys AG and Xencor signed a worldwide exclusive license and collaboration agreement. The agreement provided MorphoSys with an exclusive worldwide license to MOR208 for the treatment of cancer and other indications. MorphoSys will be solely responsible for further clinical development after successful completion of the phase 1/2a clinical trial. MorphoSys plans to initiate additional clinical trials for MOR208 in non-Hodgkin's lymphoma (NHL) and acute lymphoblastic leukemia (ALL) by year-end.
