Encouraging clinical trial data from Memorial Sloan Kettering Cancer Center (MSK) will be featured in this year's American Association for Cancer Research (AACR) Annual Meeting press program and presented as part of the Precision Medicine Early Clinical Trial Plenary Session. Alexander Drilon, MD, Assistant Attending Physician in the Developmental Therapeutics Clinic and the Thoracic Oncology Service, will report results from the international phase I STARTRK-1 and STARTRK-2 clinical trials, which assessed entrectinib as a treatment for patients with advanced solid tumors harboring gene rearrangements and of which he is principal investigator at MSK.
According to combined results from the two trials, the investigational anticancer therapeutic entrectinib -- which targets a family of proteins called TrkA/B/C, ROS1, and ALK -- was safe and 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 who had not previously been treated with Trk-, ROS1-, or ALK-directed targeted therapeutics. A phase II basket study is ongoing to determine whether these early results can be confirmed in a much larger cohort of patients.
"Our work highlights how responses to entrectinib therapy both can be highly effective and can result in long-term disease control across a number of histologies," said Dr. Drilon. "We look forward to conducting further research through the STARTRK-2 phase II trial and are hopeful that treatment with entrectinib in patients with a range of advanced or metastatic solid tumors harboring NTRK1/2/3, ROS1, or ALK gene fusions will result in very meaningful benefit."
In September 2015, initial results from the two phase I trials 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 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.
The remainder of the 12 patients who responded to entrectinib had partial responses. These responses were seen for patients with a variety of types of cancer: NSCLC; colorectal cancer; mammary analog secretory carcinoma of the salivary gland with NTRK1/2/3 gene fusions; NSCLC with ROS1 gene fusions; and NSCLC and colorectal cancer with ALK gene fusions.
MSK's Developmental Therapeutics Clinic is composed of a multidisease team of doctors, nurses, and researchers committed to the development of targeted inhibitors for patients with all types of cancer. Many of the studies conducted are first-in-human trials of experimental drugs or drug combinations that have shown promise in laboratory studies.
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