MorphoSys AG has announced the presentation of clinical data from the exploratory phase 2 COSMOS trial. The trial evaluates MorphoSys's proprietary haemato-oncological drug candidate MOR208 in combination with the cancer drug idelalisib in patients with relapsed or refractory chronic lymphocytic leukaemia (CLL) and small lymphocytic lymphoma (SLL), who progressed on or were intolerant to ibrutinib therapy. Data presented in a poster presentation on June 15, 2018, at the 23rd European Haematology Association (EHA) Annual Meeting in Stockholm/Sweden. MOR208 is an investigational Fc-enhanced humanized monoclonal antibody directed against CD19 in clinical development for the treatment of B cell malignancies.
"Patients with CLL after failure of ibrutinib therapy are in need of more therapeutic options. We are encouraged by the initial and, for the most part, still ongoing responses observed in this heavily pretreated patient population in our exploratory trial with MOR208 plus idelalisib," commented Dr. Malte Peters, chief development officer of MorphoSys AG. "Overall, this shows the potential medical application of MOR208 in additional B cell malignancies. The data shows that MOR208 may be combined with other cancer drugs used in hematological malignancies, including PI3K inhibitors. We look forward to the upcoming results from the second cohort of MOR208 plus venetoclax of our ongoing COSMOS study which we expect later this year."
COSMOS is a phase 2, two-cohort, open-label, multicenter study evaluating the preliminary safety and efficacy of MOR208 combined with idelalisib (cohort A) or venetoclax (cohort B) in patients with r/r CLL/SLL previously treated with Bruton's Tyrosine Kinase inhibitor (BTKi) ibrutinib.
Data presented at EHA 2018 comprise preliminary safety and efficacy data on all 11 patients enrolled into cohort A (cut-off date: January 29, 2018). Patients enrolled had received a median of five prior treatment lines (range: 2-9 prior lines). Nine out of the eleven patients enrolled (82%) had discontinued prior ibrutinib treatment due to progressive disease and two patients (18%) due to toxicity.
The most common treatment-emerging adverse events (TEAEs) of grade 3 or higher were haematologic, with neutropenia observed for four patients (36%) and anemia for three patients (27%) being the most common reported events. Ten treatment-emergent serious adverse events (SAEs) were reported in five patients (45%) none of them being fatal. All except one of the six treatment-related SAEs reported for three patients (27%) were suspected to idelalisib.
According to the preliminary efficacy analysis conducted by the investigators, overall response rate (ORR) was 82%, including one complete response (CR, 9%) confirmed by bone marrow biopsy and eight partial responses (PR, 73%). In addition, two patients (18%) showed stable disease. The median observation time was 4.2 months. At the time of data-cut off, six patients continued treatment. One patient with a very good partial response according to response criteria was taken off the study to receive stem cell transplantation. Two previously responding patients had to discontinue the study due to progressive disease. Two patients (one PR, one stable disease SD) discontinued due to adverse events.
CD19 is broadly and homogeneously expressed across different B cell malignancies including DLBCL and CLL. CD19 has been reported to enhance B cell receptor (BCR) signaling, which is assumed important for B cell survival, making CD19 a potential target in B cell malignancies.
MOR208 (previously Xmab(R)5574) is an investigational humanized Fc-engineered monoclonal antibody directed against CD19. Fc-modification of MOR208 is intended to lead to a significant potentiation of antibody-dependent cell-mediated cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP), thus aiming to improve a key mechanism of tumor cell killing. MOR208 has been observed in preclinical models to induce direct apoptosis by binding to CD19, which is assumed to be a crucial component for B cell receptor (BCR) signaling.
MorphoSys is clinically investigating MOR208 as a therapeutic option in B cell malignancies in a number of ongoing combination trials. An open-label phase 2 combination trial (L-MIND study) is investigating the safety and efficacy of MOR208 in combination with lenalidomide in patients with relapsed/refractory DLBCL who are not eligible for high-dose chemotherapy (HDC) and autologous stem cell transplantation (ASCT). Based on interim data from L-MIND, in October 2017 the FDA granted Breakthrough Therapy Designation for MOR208 plus lenalidomide in this patient population. The pivotal phase 2/3 B-MIND study is designed to investigate MOR208 in combination with the chemotherapeutic agent bendamustine in patients with relapsed/refractory DLBCL who are not eligible for high-dose chemotherapy (HDC) and autologous stem cell transplantation (ASCT) in comparison to the combination of the anti-CD20 antibody rituximab plus bendamustine. In addition, MOR208 is currently being investigated in patients with relapsed/refractory CLL/SLL after discontinuation of a prior Bruton tyrosine kinase (BTK) inhibitor therapy (e.g. ibrutinib) in combination with idelalisib or venetoclax.
MorphoSys is a late-stage, biopharmaceutical company devoted to the development of innovative and differentiated therapies for patients suffering from serious diseases. Based on its technological leadership in generating antibodies, MorphoSys, together with its partners, has developed and contributed to the development of more than 100 product candidates, of which 28 are currently in clinical development. This broad pipeline spans MorphoSys's two business segments: Proprietary Development, in which the Company invests in product candidates for its own account, and Partnered Discovery, in which product candidates are developed exclusively for a variety of Pharma and Biotech partners. In 2017, Tremfya(R) (guselkumab), marketed by Janssen, became the first therapeutic antibody based on MorphoSys's proprietary technology to receive marketing approval for the treatment of moderate to severe plaque psoriasis in the United States, the European Union and Canada. MorphoSys is listed on the Frankfurt Stock Exchange and on the US stock exchange Nasdaq, under the symbol MOR.