(ChemotherapyAdvisor) – The novel oral selective AKT pathway inhibitor ARQ 092 exhibits a manageable safety profile among patients with advanced solid tumors, according to the authors of a first in-human phase 1 study presented at the American Association for Cancer Research (AACR) Annual Meeting 2013, in Washington, DC.
“AKT is a signal transduction pathway crucially involved in the growth, survival, and metabolism of cancer cells,” said Mansoor N. Saleh, MD, of the University of Alabama Comprehensive Cancer Center in Birmingham, GA.
“Many of the signaling pathways disrupted by commonly seen cancer-causing mutations merge into the AKT pathway,” Dr. Saleh noted. The AKT pathway is also frequently amplified and mutated in the tumors of patients who relapse following initial therapy, he said.
Continue Reading
Dr. Saleh and coauthors tested the safety and activity of the novel oral ATP-independent AKT inhibitor ARQ 092 among a total of 22 patients with advanced and metastatic solid tumor cancers, the most frequent of which were colorectal cancer (n=4), endometrial (n=4) and neuroendocrine tumors (n=3).
Skin toxicity and hyperglycemia were common but not dose-limiting, Dr. Saleh said. Hyperglycemia followed by rash “may represent a differential feature of ARQ 092 in this class,” he noted.
“When we see hyperglycemia, we know that the drug is active in patients,” Dr. Saleh explained. “We can ameliorate the high blood sugar, potentially allowing us to achieve drug levels that will be therapeutically active.”
The maximum tolerated dose has not yet been identified, but once it is, the team will test ARQ 092 for efficacy, Dr. Saleh said. Thus far, the study has confirmed that 80-mg daily is not well tolerated, he noted.
