December 15, 2015 | by Elise Lamar
Among studies reported by City of Hope clinicians at the recent American Society of Hematology (ASH) meeting was a phase 1 trial of an “immunoconjugate” drug called SGN-CD33A. The drug is being tested as a novel antibody targeting acute myelogenous leukemia (AML).
The multi-institutional study represents the first step in preparation for future trials of the drug’s effectiveness in AML patients, particularly those with limited treatment options. The study is ongoing, but City of Hope oncologist Anthony S. Stein, M.D., reported encouraging signs in the trial, designed primarily to determine safe drug doses.
“For the last twenty years, the standard AML treatment has been an intensive regimen of two cytotoxic drugs,” said Stein, who was principal investigator of the City of Hope arm of the trial. “These treatments can be successful, particularly in younger people, but patients over 65 often don’t tolerate the chemotherapy well or decline the procedure. Thus, effective therapies for these older patients represent a totally unmet need.”
SGN-CD33A may fill that need. Biochemically, it is a monoclonal antibody that kills AML cells in two steps. First, the antibody recognizes and latches onto a receptor protein called CD33, which studs the surface of most AML tumor cells but is largely absent from mature normal blood cells. Then, once locked on, the antibody drags a tethered cell-killing drug inside the cancer cell, Trojan horse-style, killing it.
Preclinical studies in blood cancer models demonstrate that SGN-CD33A is more effective in killing AML cells and potentially safer than previously developed immunoconjugate drugs. The clinical trial reported by Stein, which includes individuals enrolled at 13 clinical centers (including City of Hope), is among the first to test SGN-CD33A in patients.
The overall results are encouraging. Adverse drug reactions, which were anticipated for a drug built to kill cells in a patient’s bone marrow, were minimal and tolerated by most of the 87 patients tested thus far. The trial’s primary goal is to determine dosage and assess how patients fare on the drug. Nonetheless, in about a third of the patients receiving high SGN-CD33A, immature leukemia cells called blasts disappeared from patients’ bone marrow — evidence of an anti-cancer effect.
Also at the ASH meeting, Stein reported a separate ongoing trial using SGN-CD33A in combination with a so-called epigenetic drug.
“In this case, we administered the antibody along with a DNA hypomethylating agent to a group of mostly untreated, elderly patients,” said Stein, who is co-director of the Gehr Family Center for Leukemia Research. “So far it looks even more promising.”
Bolstered by these findings, Stein and colleagues are now launching trials employing a similar drug combination in younger AML patients in an effort to rouse a more robust anti-cancer response and increase remission rates.
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