Forty Seven’s anti-CD47 combo shows promise in non-Hodgkin lymphoma

An immunotherapy combining Roche’s blood cancer drug Rituxan and an anti-CD47 drug developed at Stanford University shrank the cancers of half the patients in a small phase 1 trial. The patients, who had non-Hodgkin lymphoma, had all either failed or relapsed after undergoing at least two other types of treatment. 

Stanford University scientists created the CD47-targeting drug, known as Hu5F-G4, after they found in 2010 that "nearly all" cancer cells mask themselves from immune attack by presenting the protein CD47. It acts as a "don’t eat me" sign to macrophages, a type of white blood cell that locates and engulfs foreign substances, microbes and cancer cells, the researchers explained in a statement. The university spun out a company, Forty Seven, to expand this work in 2016. 

Hu5F-G4 is in multiple clinical trials, both as a monotherapy and in combination with Rituxan (rituximab) and Eli Lilly and Merck’s Erbitux (cetuximab). It’s being tested with Rituxan because the antibody has been shown to boost "eat me" signals. The Rituxan/Hu5F-G4 combination has shown promise in animal models of human cancers, but this study, which appears in the New England Journal of Medicine, is the first published result of this treatment in humans. 

The investigators administered a priming dose and weekly maintenance doses of the combination to 22 patients with relapsed or refractory non-Hodgkin lymphoma. Fifteen of the patients had diffuse large-cell B-cell lymphoma, and the remaining seven had follicular lymphoma. The patients had undergone a median of four previous treatments—the range was two to 10 treatments—and 95% of them had not previously responded to Rituxan, they said in the study. 

Half of the patients had an objective response to the treatment. Of these 11 patients, eight had a complete response, that is, they had no sign of cancer after treatment. Three patients in the trial did not respond to the treatment and died of their cancer. 

Some patients experienced anemia and reactions at their injection site, but Ranjana Advani, M.D., the paper’s lead author and a professor of medicine at Stanford, was heartened that the side effects were relatively minor. The team expected patients to develop anemia, a known effect of targeting CD47, so they used a priming dose of the treatment to keep it under control. 

"It's very exciting to have a potentially new class of immunotherapy like this," Advani said. "For the first time we have an antibody that activates macrophages against cancer and appears to be safe for use in humans."

Forty Seven funded the study, alongside the Leukemia and Lymphoma Society. The Menlo Park, California-based biotech has formally partnered with Merck KgAa and Genentech to test Hu5F-G4 combinations. It is running a test with the former’s Bavencio (avelumab) in ovarian cancer and the latter’s Tecentriq (atezolizumab) in bladder cancer and acute myeloid leukemia.

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