CD20xCD3 Bispecific Antibody in Relapsed or Refractory B-Cell Non-Hodgkin Lymphoma
New data was recently presented at the 2018 ASH Annual Meeting for REGN1979 in patients with relapsed or refractory (R/R) B-cell non-Hodgkin lymphoma (B-NHL), including promising clinical results in follicular lymphoma (FL).
In this phase I proof-of-concept trial, REGN1979 demonstrated an acceptable safety and tolerability profile with no observed dose-limiting toxicities (DLTs). There were no clinically significant neurotoxicities, including no occurrence of seizures or encephalopathy. REGN1979 is a wholly owned, investigational, full-length bispecific monoclonal antibody designed to trigger tumor killing by binding CD3 on immune system T-cells and CD20 on B-cell malignancies.
In the data presented at the conference (Abstract 626), heavily pre-treated patients with R/R FL grades 1-3a who received REGN1979 doses of 5 mg to 40 mg, experienced a 100 percent overall response rate (ORR) (8 complete responses [CR] and 2 partial responses [PR]); 90 percent of responders maintained a response during treatment. Based on these data, there are plans to initiate a potentially registrational phase II trial investigating REGN1979 in R/R FL in 2019.
REGN1979 also showed encouraging dose-dependent clinical activity in heavily pre-treated patients with R/R diffuse large B-cell lymphoma (DLBCL). Among patients receiving doses between 5 mg and 12 mg, the ORR was 18 percent (2 of 11 patients, including 1 CR and 1 PR). At doses of 18 mg to 40 mg, the ORR increased to 60 percent (6 of 10 patients, including 2 CR and 4 PR). Continued dose-escalation in DLBCL is planned.
The objectives for this ongoing phase I proof-of-concept trial are to assess safety, tolerability, and efficacy of REGN1979 monotherapy. The data presented at ASH included a total of 68 patients with R/R B-NHL who were treated with REGN1979. These patients had received a median of three prior therapies, including an anti-CD20 therapy. As of September 2018, 14 patients had completed treatment, 13 patients remained on treatment, and 41 had discontinued treatment. The most common reason for treatment discontinuation was progressive disease (27 patients). Two patients discontinued treatment due to a treatment-emergent adverse event (TEAE; grade 3 hemolysis and grade 3 fatigue).
In the trial, the most common TEAEs occurring in at least 25 percent of patients were pyrexia, chills, cytokine release syndrome (CRS), fatigue, increased C-reactive protein, anemia, hypotension, infusion-related reaction (IRR), and nausea. IRR and CRS events were generally mild to moderate in severity, and neither resulted in trial discontinuations. Three patients in the trial died due to adverse events. Of these, one death in a patient with a tumor involving the gastric lining who experienced a gastric perforation was attributed to REGN1979.
REGN1979 was granted Orphan Drug Designation by the FDA for the treatment of DLBCL in 2017. REGN1979, REGN4018 (MUC16xCD3 bispecific antibody), and REGN5458 (BCMAxCD3 bispecific antibody) are currently under clinical development for B-NHL, ovarian cancer, and multiple myeloma, respectively, and their safety and efficacy have not been evaluated by any regulatory authority.