MorphoSys is asking the U.S. Food and Drug Administration (FDA) to approve its CD19 antibody tafasitamab, in combination with Revlimid (lenalidomide), to treat patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), the company announced.
The biologics license application (BLA) submitted to the agency included data from the L-MIND Phase 2 clinical trial (NCT02399085) testing the combination, and the Re-MIND retrospective observational study assessing the outcomes of matched DLBCL patients receiving Revlimid alone.
The studies demonstrated superior response rates and survival outcomes among people receiving the tafasitamab and Revlimid combination, compared to Revlimid alone. The FDA has 60 days to determine whether the application is complete and acceptable for filing.
“The BLA submission marks a significant milestone in MorphoSys’ history and demonstrates our dedication to address the high medical need in relapsed or refractory DLBCL,” Malte Peters, MD, chief development officer of MorphoSys, said in a press release. “If approved, tafasitamab and lenalidomide could become an alternative treatment option for patients with this serious disease.”
Tafasitamab (formerly known as MOR208) is an antibody that targets a protein called CD19, which is present in high amounts at the surface of lymphoma cells. While several CD19 antibodies are in development for lymphoma treatment, tafasitamab has a special modification meant to boost immune responses to cancer cells, increasing tumor cell death.
The ongoing L-MIND clinical trial is testing tafasitamab, in combination with Revlimid, as a treatment for DLBCL patients who are unfit for high-dose chemotherapy and stem cell transplant, and have received one to three prior lines of therapy, including a CD20-targeted therapy such as rituximab.
The study’s main goal was to determine the proportion of patients responding, partially or completely, to the combination. Secondary measures included assessing those with at least stable disease, duration of response, time to disease progression or death, overall survival, and safety.
Results presented at the 2019 International Conference on Malignant Lymphoma showed that L-MIND met its primary objective, with more patients responding to treatment (60%), compared to published data on treatment with tafasitamab (27.5%) and Revlimid alone.
This update included data from all 80 patients in the trial, who had been followed for at least one year. Their median age was 72, and they had received a median of two prior therapies.
Complete responses were attained by 43% of patients, and 82% of them were confirmed on positron emission tomography scans. Responses were also durable, lasting a median of 21.7 months.
Patients lived without signs of disease progression for a median of 12.1 months, and more than half were alive after a median follow-up of 19.6 months. The one-year survival rate in these patients was 73.3%.
“The results from the L-MIND study … are very encouraging. We are particularly pleased to see such a high complete response rate and a prolonged response duration, which is unusual in this population of relapsed or refractory DLBCL,” professor Gilles Salles, lead investigator of L-MIND, said in a press release reporting the findings.
The combination of tafasitamab and Revlimid was generally well-tolerated. The most common serious or worse treatment-emergent adverse events were low levels of neutrophils (a type of immune cell), low platelet counts, and anemia. Reductions in Revlimid doses were required in 43% of patients.
Aiming to compare L-MIND findings to those of Revlimid treatment alone, researchers designed Re-MIND, a retrospective observational study that included data from matched patients receiving Revlimid in Europe and the U.S. in a real-world clinical setting.
Re-MIND collected data from 490 relapsed or refractory DLBCL patients, who were also unfit for stem cell transplant. After examining specific qualification criteria such as age, gender, and number of prior therapies, researchers ended up with a subset of 76 patients, matched for 76 of the 80 L-MIND patients.
Results revealed in October 2019 showed that response rates among the 76 patients receiving the tafasitamab combination were significantly higher (at 67.1%) than among those on Revlimid alone (34.2%), meeting the trial’s primary objective.
The addition of tafasitamab also tripled complete responses (39.5% vs. 11.8%) and reduced the risk of disease worsening or death by 53%.
“I’m very excited about this real-world data approach of the Re-MIND trial to isolate a single-agent contribution of tafasitamab in combination with lenalidomide in a matched patient population in r/r DLBCL,” Pier Luigi Zinzani, MD, PhD, one of the lead investigators in Re-MIND, said in another press release. “This study further strengthens the synergistic effect of tafasitamab and lenalidomide, as already observed in the L-MIND trial.”
MorphoSys has also announced its intention to seek tafasitamab’s approval, in combination with Revlimid, for the treatment of relapsed or refractory DLBCL patients in Europe. A marketing authorization application is expected to be submitted to the European Medicines Agency by mid-2020.
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