Forty Seven, Acerta Collaborate to Test Triple Combo Therapy on DLBCL Patients

Forty Seven and Acerta Pharma are collaborating to test a triple combination of the investigational 5F9 plus Rituxan (rituximab) and Calquence (acalabrutinib) in patients with diffuse large B-cell lymphoma (DLBCL).

The partnership builds on prior Phase 1b data that showed a combination of Forty Seven’s 5F9 and Rituxan was safe and eliminated tumors in one-third of DLBCL patients who had already failed two prior treatment approaches. Acerta’s BTK inhibitor Calquence is now going to be included in the combination to optimize responses to treatment.

“We are looking forward to evaluating this novel triple combination of 5F9 and [Rituxan] with [Calquence],” Andrew Mortlock, Acerta’s chief scientific officer, said in a press release.

The mainstay treatment for virtually all B-cell non-Hodgkin’s lymphomas includes CD20-targeting antibodies such as Rituxan (from Biogen and Genentech, which is part of the Roche group). However, patients may develop resistance to Rituxan, which severely worsens their prognosis.

Forty Seven’s macrophage checkpoint inhibitor Hu5F9-G4 — or simply 5F9 — is an antibody that targets the CD47 factor, blocking the “don’t eat me” signal used by cancer cells to avoid being ingested by macrophages, a kind of immune cell that engulfs invaders.

The investigational therapy — which received the Fast Track status for DLBCL and follicular lymphoma — works much like other immune checkpoint inhibitors, but instead of activating T-cells, it improves the ability of macrophages to identify cancer cells and eliminate them.

The promising results from the combination of 5F9 and Rituxan prompted the development of the triple combination regimen, which could produce even better anti-tumor responses.

Forty Seven recently extended its collaboration with Genentech to study a combination of 5F9 plus Rituxan and Tecentriq (atezolizumab) in the same patient population.

Now, the company is partnering with Acerta (a member of the AstraZeneca group) to study Calquence as part of the 5F9-Rituxan mix. The trial is being sponsored by Acerta.

Calquence — already approved for mantle cell lymphoma treatment — is an orally administered medicine that works by blocking the Bruton tyrosine kinase (BTK) needed for the survival and proliferation of B-cells, including lymphoma cells.

In 2018, Acerta established the PRISM Phase 1 platform trial (NCT03527147) to study a number of Calquence combinations in non-Hodgkin’s lymphoma patients who had failed prior treatments.

“With [Calquence], we have a compound that optimally targets Bruton tyrosine kinase (BTK). 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,” Mortlock added.

Added Ian W. Flinn, MD, PhD, chair of the PRISM study and director of the Lymphoma Research Program at Sarah Cannon Research Institute: “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.”

In addition to this triple treatment regimen, Forty Seven is evaluating 5F9 in several combination regimens for blood and solid cancers as part of their 5F9 development program.

“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,” Craig Gibbs, PhD, chief business officer at Forty Seven, said.