Antibody shows activity in relapsed/refractory NHL

SAN FRANCISCO—The anti-CD19 antibody M0R208 has demonstrated encouraging single-agent activity in patients with relapsed or refractory non-Hodgkin lymphoma (NHL), according to a presenter at the 2014 ASH Annual Meeting.

“It is encouraging to see results in an NHL study that selects a different target than CD20,” said Kristie Blum, MD, of The Ohio State University in Columbus.

“In particular, it is good to see activity in elderly large-cell lymphoma patients.”

MOR208 is an Fc-engineered humanized monoclonal antibody that targets the CD19 antigen.

“It possesses significantly enhanced antibody-dependent cell-mediated cytotoxicity, a key mechanism for tumor cell killing,” Dr Blum explained. “We have seen previous responses in diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL).”

In fact, MOR208 recently received fast-track designation from the US Food and Drug Administration to treat DLBCL.

At ASH, Dr Blum reported on a non-randomized, phase 2a study designed to assess the efficacy and safety of single-agent MOR208 in adults with relapsed or refractory NHL (abstract 3089). The trial was sponsored by MorphoSys AG, the company developing MOR208.

The study included 89 patients—35 with DLBCL, 31 with FL, 12 with mantle cell lymphoma (MCL), and 11 with other indolent NHLs (iNHLs). The patients had a median age of 67 years, were previously treated with rituximab, and were not candidates for high-dose therapy with stem cell support.

The patients were treated over 56 days. MOR208 was given intravenously at 12 mg/kg as 8 weekly doses on days 1, 8, 15, and 22 of each cycle. Patients with at least stable disease continued treatment for another cycle.

After completing 12 weekly doses of treatment, responding patients received maintenance MOR208 every 2 or 4 weeks, depending on the investigator’s decision, until progression.

The results showed overall response rates of 26% for DLBCL patients, 23% for FL patients, and 36% in iNHL patients. No MCL patients responded.

There were 2 complete responses in the DLBCL cohort and 1 complete response each in the FL and iNHL cohorts. Response duration reached 13.8 months.

The drug was well-tolerated with an acceptable toxicity profile, Dr Blum said. The most frequently reported treatment-emergent adverse events of any grade were thrombocytopenia, anemia, and neutropenia, all at 9%.

Infusion-related reactions were reported in 9% of patients and were typically grade 1 or 2. There have been no treatment-related deaths.

Protocols are being developed for trials that combine MOR208 with other anti-lymphoma therapies, with plans to open phase 1/2 trials by mid-2015.

“We plan to take the drug forward in combination with bendamustine or lenalidomide plus rituximab,” Dr Blum said. “By adding the drug into a bendamustine-rituximab combination, we will hit 2 different targets and may see synergistic cell killing.”

SAN FRANCISCO—The anti-CD19 antibody M0R208 has demonstrated encouraging single-agent activity in patients with relapsed or refractory non-Hodgkin lymphoma (NHL), according to a presenter at the 2014 ASH Annual Meeting.

“It is encouraging to see results in an NHL study that selects a different target than CD20,” said Kristie Blum, MD, of The Ohio State University in Columbus.

“In particular, it is good to see activity in elderly large-cell lymphoma patients.”

MOR208 is an Fc-engineered humanized monoclonal antibody that targets the CD19 antigen.

“It possesses significantly enhanced antibody-dependent cell-mediated cytotoxicity, a key mechanism for tumor cell killing,” Dr Blum explained. “We have seen previous responses in diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL).”

In fact, MOR208 recently received fast-track designation from the US Food and Drug Administration to treat DLBCL.

At ASH, Dr Blum reported on a non-randomized, phase 2a study designed to assess the efficacy and safety of single-agent MOR208 in adults with relapsed or refractory NHL (abstract 3089). The trial was sponsored by MorphoSys AG, the company developing MOR208.

The study included 89 patients—35 with DLBCL, 31 with FL, 12 with mantle cell lymphoma (MCL), and 11 with other indolent NHLs (iNHLs). The patients had a median age of 67 years, were previously treated with rituximab, and were not candidates for high-dose therapy with stem cell support.

The patients were treated over 56 days. MOR208 was given intravenously at 12 mg/kg as 8 weekly doses on days 1, 8, 15, and 22 of each cycle. Patients with at least stable disease continued treatment for another cycle.

After completing 12 weekly doses of treatment, responding patients received maintenance MOR208 every 2 or 4 weeks, depending on the investigator’s decision, until progression.

The results showed overall response rates of 26% for DLBCL patients, 23% for FL patients, and 36% in iNHL patients. No MCL patients responded.

There were 2 complete responses in the DLBCL cohort and 1 complete response each in the FL and iNHL cohorts. Response duration reached 13.8 months.

The drug was well-tolerated with an acceptable toxicity profile, Dr Blum said. The most frequently reported treatment-emergent adverse events of any grade were thrombocytopenia, anemia, and neutropenia, all at 9%.

Infusion-related reactions were reported in 9% of patients and were typically grade 1 or 2. There have been no treatment-related deaths.

Protocols are being developed for trials that combine MOR208 with other anti-lymphoma therapies, with plans to open phase 1/2 trials by mid-2015.

“We plan to take the drug forward in combination with bendamustine or lenalidomide plus rituximab,” Dr Blum said. “By adding the drug into a bendamustine-rituximab combination, we will hit 2 different targets and may see synergistic cell killing.”

SAN FRANCISCO—The anti-CD19 antibody M0R208 has demonstrated encouraging single-agent activity in patients with relapsed or refractory non-Hodgkin lymphoma (NHL), according to a presenter at the 2014 ASH Annual Meeting.

“It is encouraging to see results in an NHL study that selects a different target than CD20,” said Kristie Blum, MD, of The Ohio State University in Columbus.

“In particular, it is good to see activity in elderly large-cell lymphoma patients.”

MOR208 is an Fc-engineered humanized monoclonal antibody that targets the CD19 antigen.

“It possesses significantly enhanced antibody-dependent cell-mediated cytotoxicity, a key mechanism for tumor cell killing,” Dr Blum explained. “We have seen previous responses in diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL).”

In fact, MOR208 recently received fast-track designation from the US Food and Drug Administration to treat DLBCL.

At ASH, Dr Blum reported on a non-randomized, phase 2a study designed to assess the efficacy and safety of single-agent MOR208 in adults with relapsed or refractory NHL (abstract 3089). The trial was sponsored by MorphoSys AG, the company developing MOR208.

The study included 89 patients—35 with DLBCL, 31 with FL, 12 with mantle cell lymphoma (MCL), and 11 with other indolent NHLs (iNHLs). The patients had a median age of 67 years, were previously treated with rituximab, and were not candidates for high-dose therapy with stem cell support.

The patients were treated over 56 days. MOR208 was given intravenously at 12 mg/kg as 8 weekly doses on days 1, 8, 15, and 22 of each cycle. Patients with at least stable disease continued treatment for another cycle.

After completing 12 weekly doses of treatment, responding patients received maintenance MOR208 every 2 or 4 weeks, depending on the investigator’s decision, until progression.

The results showed overall response rates of 26% for DLBCL patients, 23% for FL patients, and 36% in iNHL patients. No MCL patients responded.

There were 2 complete responses in the DLBCL cohort and 1 complete response each in the FL and iNHL cohorts. Response duration reached 13.8 months.

The drug was well-tolerated with an acceptable toxicity profile, Dr Blum said. The most frequently reported treatment-emergent adverse events of any grade were thrombocytopenia, anemia, and neutropenia, all at 9%.

Infusion-related reactions were reported in 9% of patients and were typically grade 1 or 2. There have been no treatment-related deaths.

Protocols are being developed for trials that combine MOR208 with other anti-lymphoma therapies, with plans to open phase 1/2 trials by mid-2015.

“We plan to take the drug forward in combination with bendamustine or lenalidomide plus rituximab,” Dr Blum said. “By adding the drug into a bendamustine-rituximab combination, we will hit 2 different targets and may see synergistic cell killing.”