Most treatments for blood cancers like acute myeloid leukemia (AML) are designed to attack the cancer cells themselves. Now, scientists at Pfizer have figured out how to make those cells even more vulnerable to direct attack—by driving them from their favorite hiding place.
Pfizer has begun a phase 1 trial of a new antibody designed to do just that, called PF-06747143, the company reported Wednesday. The drug is being tried in patients with AML, but preclinical studies suggest the approach may be applicable to other blood cancers, including non-Hodgkin lymphoma and multiple myeloma, according to a press release.
In mouse models of all three cancers, PF-06747143 killed more cancer cells than standard chemotherapy, regardless of whether it was administered as a solo treatment or in combination with chemo, the researchers reported. In mouse models of AML, the drug tamped down cancer cells by 96% when used on its own, and by more than 99% when given with the chemo agents daunorubicin and cytarabine. The research was published in the American Society of Hematology’s journal Blood Advances.
The key to the new approach is that PF-06747143 moves the cancer cells out of the bone marrow and into the bloodstream, where they become more vulnerable to traditional treatments like chemotherapy. The drug also seems to attack and kill the cells itself. Therefore, it’s possible that it could be used as a standalone treatment in people who are not good candidates for chemo, or in combination with traditional therapies, said Flavia Pernasetti, Ph.D., of Pfizer Oncology Research and Development, in the statement.
"One of the major limitations we see in treating blood cancers is the failure to clear cancer cells from the bone marrow," Pernasetti said. “Because the bone marrow allows the cancer cells to flourish, removing these cells is an essential step in treating these malignancies effectively.”
Pernasetti’s team designed the antibody by focusing on a receptor that controls the movement of cells into the bone marrow. They figured out how to inhibit the receptor so AML cells would move into the less-protected bloodstream, then they improved upon the antibody by giving it the ability to attack cancer cells directly.
Pfizer has been doubling down on its oncology pipeline over the past several years, and charting some notable successes including breast cancer drug Ibrance and lung cancer treatment Xalkori. It has also been playing catch-up in the red-hot market for immuno-oncology treatments, recently scoring an FDA approval for Bavencio, a checkpoint inhibitor to target the skin cancer Merkel cell carcinoma.
Pernasetti said her team is “very excited” to see how PF-06747143 performs in the phase 1 clinical trial. The trial is recruiting AML patients at hospitals in Arizona, Illinois and North Carolina, and will evaluate the drug as a standalone treatment and in combination with chemotherapy.