Triple-Therapy Combo Without Chemo to Be Studied in DLBCL

AstraZeneca’s hematology center, Acerta Pharma, will launch a clinical trial to study a new triple-therapy combination to treat diffuse large B-cell lymphoma (DLBCL). The trial announced today will combine Acerta’s acalabrutinib (Calquence) with 5F9, a monoclonal antibody from Forty Seven, and rituximab.

Based on proof of concept studies, the immunotherapy-targeted therapy combination could offer a new option for DLBCL with fewer adverse effects, which the clinical trial will explore.

The collaboration between Acerta Pharma and Forty Seven follows results from a phase 1B trial of 5F9 plus rituximab in patients with non-Hodgkin lymphoma, which were presented last year at the American Society of Clinical Oncology and appeared in the New England Journal of Medicine in November 2018. In that study, 5F9 was tested in patients with DLBCL and follicular lymphoma, with 50% of patients having at least a partial response and 36% having a complete response. The treatment was safe and well tolerated, and the maximum dose was not defined.

According to a statement from Forty Seven, 5F9 binds to CD47, a “don’t eat me signal” that is overexpressed on cancer cells. The treatment takes the “brakes off” the macrophages, allowing them to engulf tumor cells in a process known as phagocytosis. This new study seeks to examine the potential of macrophages with a treatment that is safe and effective and has fewer adverse effects than current options. Acalabrutinib is an inhibitor of Bruton tyrosine kinase (BTK); blocking this signal reduces B-cell proliferation.

“We are looking forward to evaluating this novel triple combination of 5F9 and rituximab with acalabrutinib. With acalabrutinib, we have a compound that optimally targets Bruton tyrosine kinase,” Andrew Mortlock, chief scientific officer at Acerta Pharma, said in a statement. “We established the PRISM platform study in 2018 with the explicit goal of exploring novel combinations and are pleased to be able to collaborate with Forty Seven to include 5F9 in this platform and bring this innovative combination of therapies to patients.”

“This combination of immunotherapy with targeted therapy has the potential to help patients with an aggressive type of lymphoma. These individual therapies have previously demonstrated activity in lymphoma without the toxicities associated with traditional cytotoxic chemotherapy,” Ian W. Flinn, MD, PhD, chair of the PRISM Study and director of the Lymphoma Research Program at Sarah Cannon Research Institute, said in the announcement.

“We are pleased to enter this collaboration with Acerta, which expands the breadth of our 5F9 development program to include an additional triplet regimen, with the potential to offer patients a treatment option that is more easily administered and the benefit of multiple distinct approaches to treating cancer,” said Craig Gibbs, PhD, chief business officer at Forty Seven Inc. “BTK inhibition has already demonstrated therapeutic potential in patients with B-cell lymphomas and we believe that harnessing this approach while also activating the macrophage component of the innate immune system could enable more benefit than either strategy alone. With today’s announcement, we are now pursuing three combination approaches reflecting our deep commitment to meeting the needs of patients with DLBCL.”