GlaxoSmithKline plc and Genmab A/S announced that the phase III study (ORCHARRD) of ofatumumab (Arzerra) plus chemotherapy versus rituximab plus chemotherapy to treat relapsed or refractory diffuse large B-cell lymphoma (DLBCL) did not meet its primary endpoint as there was no statistically significant difference in progression free survival (PFS) between the treatment arms.
There were no differences in adverse events (AEs) leading to treatment discontinuation, Grade >3 AEs, severe adverse events (SAEs), or fatal SAEs between the treatment arms. However, there were more dose interruptions and delays due to infusion reactions and increased serum creatinine in the ofatumumab plus chemotherapy arm, which require further analysis.
“We are disappointed that the ORCHARRD study did not meet its primary endpoint. We will further analyze these results to better understand the findings and how they add to our collective knowledge of this disease,” said Dr Rafael Amado, head of oncology R&D, GlaxoSmithKline.
“We plan to submit detailed data from the ofatumumab ORCHARRD study in DLBCL for presentation at a medical conference later this year, which we hope will provide further clarity on today’s headline results. Based on today’s results we are unlikely to move forward with a regulatory filing,” said Jan van de Winkel, chief executive officer of Genmab.
This pivotal phase III randomized study included 447 patients who were refractory to, or had relapsed following, first-line treatment with rituximab in combination with a chemotherapy regimen containing anthracycline or anthracenedione, and were eligible for autologous stem cell transplant (ASCT). Patients in the study were randomized 1:1 to receive three cycles of either ofatumumab or rituximab in combination with DHAP (dexamethasone, cytarabine and cisplatin) salvage chemotherapy. After the third treatment cycle, patients who obtained a complete or partial response received high dose chemotherapy followed by ASCT. The primary endpoint of the study was progression free survival.
DLBCL is the most common form of non-Hodgkin lymphoma (NHL), and is an aggressive (fast-growing) lymphoma or cancer of the B-cells. DLBCL is the most common lymphoid malignancy in adults, accounting for 30% of all NHL in the Western world. Approximately 38,000 new cases of DLBCL occur annually in the US, Japan and five major European markets.
Ofatumumab—a human monoclonal antibody which targets an epitope on the CD20 molecule encompassing parts of the small and large extracellular loops—is not approved or licensed anywhere in the world for the treatment of DLBCL.
Genmab is a publicly traded, international biotechnology company specializing in the creation and development of differentiated human antibody therapeutics for the treatment of cancer.