CytRx Corporation (NASDAQ:CYTR), a biopharmaceutical company engaged in the development and commercialization of human therapeutics, today announced the initiation of a dose escalation study with its oncology drug candidate tamibarotene combined with TRISENOX® (arsenic trioxide) injection (marketed by Cephalon, Inc.) in patients with relapsed acute promyelocytic leukemia (APL). There are two primary trial objectives. The first is to determine the safety and preliminary efficacy of combining tamibarotene with arsenic trioxide as a treatment for relapsed or refractory APL. The second objective is to determine the appropriate dose for future clinical trials in which CytRx would test the utility of the tamibarotene/arsenic trioxide combination as a first-line treatment for subjects who prefer not to be exposed to anthracyclines. The dose escalation study is being financed jointly by CytRx and Cephalon.
“This trial represents an important step in our ultimate goal of evaluating tamibarotene as a first-line treatment for APL,” said Steven Kriegsman, CytRx President and CEO. The majority of patients with newly diagnosed APL are currently treated with all-trans retinoic acid (ATRA) plus anthracycline-based chemotherapy, typically followed by maintenance with ATRA with or without low-dose chemotherapy. “This clinical trial will expand upon our current ongoing STAR-1 registration clinical trial that is evaluating tamibarotene’s efficacy and safety as a third-line treatment,” according to Mr. Kriegsman.
In the multi-center Phase I dose escalation trial, between 16 and 22 relapsed APL subjects in three dose groups will be treated with 2-3 six-week cycles of intravenous arsenic trioxide and self-administered oral tamibarotene tablets with 2-6 weeks between cycles. Initially, three to six subjects will be entered in the group receiving the lowest dose. If no more than one dose-limiting toxic event is reported, the dose will be escalated to the next cohort and this process will continue until the maximum dose is achieved or the maximum tolerated dose (MTD) is identified. A total of 10 subjects will be enrolled at the maximum dose or the MTD for one or two additional cycles of therapy and evaluated for disease remission. The dose for the subsequent Phase 2 trial will be the dose at which at least five of six subjects tolerate the treatment or the maximum dose used in this trial.
“We hypothesize that the combination of tamibarotene and arsenic trioxide will result in a similar complete response rate as the ATRA and arsenic trioxide combination, but with decreased toxicities, such as hyperleukocytosis, APL differentiation syndrome and rash and potentially a lower relapse rate,” said Jessica K. Altman M.D., Assistant Professor of Medicine at Northwestern University Feinberg School of Medicine. Dr. Martin S. Tallman, Professor of Medicine stated, “Because tamibarotene appears to be more potent and more selective than ATRA, we anticipate that the tamibarotene/arsenic trioxide combination may be more effective and less prone to drug resistance than ATRA combined with arsenic trioxide.” Drs. Altman and Tallman will serve as principal co-investigators for the trial.
There are currently no approved third-line treatment options for refractory APL subjects, an annual market that CytRx estimates at approximately $20 million in the United States and $25 million in Europe. The estimated annual market potential in the U.S. and Europe for an expanded label for tamibarotene that includes refractory, maintenance and front-line therapy is up to $150 million, As announced recently, CytRx has been granted European Orphan Drug status for tamibarotene as a third-line APL. While currently focused on U.S. approval for tamibarotene, CytRx considers Orphan Drug status as an important step in its future plans to pursue European Union approval for tamibarotene as a treatment for APL.