The investigational anticancer therapeutic entrectinib, which targets the proteins TrkA/B/C, ROS1, and ALK, was safe, tolerable, and showed signs of clinical activity in patients who had several different types of cancer with NTRK1/2/3, ROS1, or ALK gene alterations and had not previously been treated with a Trk-, ROS1-, or ALK-directed targeted therapeutic, according to combined results from two phase I clinical trials presented at the AACR Annual Meeting 2016, April 16-20.
“Alterations called fusions involving the NTRK1/2/3, ROS1, and ALK genes are detected in a variety of types of cancer,” said Alexander Drilon, MD, assistant attending physician of the Developmental Therapeutics Clinic and the Thoracic Oncology Service and principal investigator of STARTRK-1 and STARTRK-2 at Memorial Sloan Kettering Cancer Center in New York.
“These fusions cause heightened activity of the TrkA/B/C, ROS1, and ALK proteins coded for by these genes, thus promoting cancer cell proliferation and survival.
“Our data show that entrectinib, a potent oral inhibitor of TrkA/B/C, ROS1, and ALK proteins, can achieve rapid and durable responses in patients with a range of advanced or metastatic solid tumours harbouring NTRK1/2/3, ROS1, or ALK gene fusions,” continued Drilon.
“A phase II clinical trial, called STARTRK-2, is ongoing to determine whether these early results can be confirmed in a much larger cohort of patients.”
In September 2015, initial results from the two phase I clinical trials, STARTRK-1 and ALKA-372-001, were reported, establishing 600 milligrams of entrectinib administered orally once daily as the recommended phase II dose.
Data from these two trials also showed an objective response rate of 72 percent among the 18 patients who met criteria for what was defined as a phase II–eligible population: the presence of NTRK1/2/3, ROS1, or ALK gene fusions in their tumours, no prior treatment with a TrkA/B/C-, ROS1-, or ALK-directed targeted therapeutic, and treatment at or above the recommended phase II dose.
The researchers are now reporting updated data for additional patients in the two trials who met the phase II eligibility criteria, as well as updated safety data in additional patients.
After a median follow-up of 11 months, 11 of the 13 patients who responded remain on the study, including one patient who had non–small cell lung cancer (NSCLC) with a ROS1 gene fusion who has had a complete response that has been maintained for more than two years.
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