Phase Ib Clinical Trial Enrolling to Evaluate Tafasitamab in Treatment-Naive DLBCL

John M. Burke, MD

John M. Burke, MD

The current standard of care for the treatment of patients with diffuse large B-cell lymphoma (DLBCL) is rituximab (Rituxan), cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP), which is associated with cure rates of 60% to 70%. However, researchers aim to improve upon these outcomes, particularly with a new phase Ib clinical trial called the First-MIND trial which will assess the safety of the combination R-CHOP plus tafasitamab (MOR208) or R-CHOP plus tafasitamab and lenalidomide (Revlimid).¹

Tafasitamab is an engineered anti-CD19 monoclonal antibody, which is expected to have a synergistic cytotoxic effect with the anti-CD20 antibody rituximab. Between 15% and 20% of patients with treatment-naïve DLBCL have low expression of CD20 in their tumors, while CD19 is expressed in over 90% of patients with DLBCL. Patients with low-CD20 expression are associated with poorer outcomes with rituximab-based regimens like R-CHOP. Because CD19 is a positive regulator of B-cell receptor signaling and is important for the activation and proliferation of B-cells, tafasitamab is an attractive target in addition to rituximab.

Tafasitamab as a monotherapy has demonstrated clinical activity as well as safety in patients with relapsed/refractory chronic lymphocytic leukemia and small lymphocytic, as well as in relapsed/refractory non-Hodgkin lymphoma (NHL). The agent demonstrated promising responses in a phase IIa clinical trial (NCT01685008), which indicated an objective response rate in relapsed/refractory patients of 26% with DLBCL, 29% with follicular lymphoma, and 27% with other indolent NHLs. Patients received tafasitamab intravenously weekly for 8 weeks. In terms of safety, the most common toxicities of any grade included infusion-related reactions (12%) and neutropenia (12%). Grade 3/4 neutropenia was observed in 8 patients (9%), and 1 patient experienced a grade 4 infusion-related reaction.²

First-MIND (NCT04134936) is an open-label, multicenter, randomized phase Ib trial enrolling 60 patients across sites in the United States and Europe. Patients must have previously untreated DLBCL with intermediate- to high-risk disease. Patients with double- or triple-hit lymphoma and transformed or composite lymphoma are excluded from the study.

Tafasitamab is given at 12 mg/kg intravenously on days 1, 8, and 15 of a 21-day cycle to all patients on trial, as well as R-CHOP treatment. Patients in the second arm will also receive lenalidomide at 25 mg orally on days 1 through 10. In the safety run-in phase, 12 patients will be enrolled to each arm, and if no unexpected safety signals arise related to treatment, 18 more patients will be enrolled in each arm.¹

In an interview withTargeted Oncology, John M. Burke, MD, associate chair of the Hematology Research Program for US Oncology and Rocky Mountain Cancer Centers, discussed the ongoing phase Ib First-MIND clinical trial of tafasitamab in combination with R-CHOP with or without lenalidomide as treatment of patients with newly diagnosed DLBCL.

TARGETED ONCOLOGY: What is the rationale for evaluating tafasitamab in this patient population?

Burke:Tafasitamab is an engineered antibody that targets CD19, and in combination with lenalidomide, it has shown excellent activity in patients with relapsed large cell lymphoma. As a result, we are interested in studying it in combination with conventional chemotherapy, R-CHOP, in patients with newly diagnosed DLBCL. Our rationale is that we want to improve on outcomes in patients with newly diagnosed DLBCL.

TARGETED ONCOLOGY: How is this trial designed?

Burke:The First-MIND trial is in progress, and [opened in] December 2019. Patients will be eligible if they have been diagnosed with previously untreated DLBCL. The design is that patients will be randomized to 1 of 2 groups. In 1 group, they will receive conventional R-CHOP therapy for 6 cycles along with tafasitamab. In the other group, they will receive the same R-CHOP and the same tafasitamab, plus lenalidomide. Lenalidomide will be given orally during all of the 6 cycles.

TARGETED ONCOLOGY: What is the goal of evaluating tafasitamab in combination with R-CHOP with or without lenalidomide in this patient population?

Burke:The primary goal of the study is to determine the safety of the 2 arms. We will get a signal as to whether both of these groups are safe. Based on that, the goal is to go on to do a larger phase III study with a primary end point of event-free survival. The goal of this study is to look at safety.

TARGETED ONCOLOGY: Looking ahead, how will this clinical trial impact the treatment of patients with newly diagnosed DLBCL if the results are positive?

Burke:After this first safety-finding study, we would have to go to a randomized phase III trial. If that trial were positive, it would change the standard of care for how to treat patients with large cell lymphoma initially. The original study that has been proposed that will be conducted first won’t be practice-changing immediately by itself.

TARGETED ONCOLOGY: Have we seen any data with tafasitamabin any other areas or lymphomas prior to this study?

Burke:There has been a phase I clinical trial of tafasitamab in patients with relapsed lymphoma. There is also evidence that it has activity in both follicular lymphoma and large cell lymphoma. There has also been a trial of tafasitamab plus lenalidomide in patients with relapsed lymphoma. That is the main research we have seen.

The plan is to keep the First-MIND trial open and enrolling for about 6 to 12 months. It’s an international study being conducted at different sites around the world.

References:

1. A Phase Ib, Open-Label, Randomized Study to Assess Safety and Preliminary Efficacy of Tafasitamab (MOR208) or Tafasitamab + Lenalidomide in Addition to R-CHOP in Patients with Newly Diagnosed Diffuse Large B-Cell Lymphoma: The First-Mind Trial. Presented at: 2019 American Society of Hematology (ASH) Annual Meeting; December 7-10, 2019; Orlando, FL.
2. Makita S. Tobinai K. Antibody therapy targeting CD19 for B-cell non-Hodgkin’s lymphoma.Ann Oncol. 2018; 29:1266.