The kinase inhibitor BLU-667, which selectively targets the oncogenic driver RET (rearranged during transfection), is demonstrating promising clinical activity against solid tumors with RET gene alterations, according to the early results of a phase I trial.
RET alterations, which can be found in almost any cancer type, occur in most patients with medullary thyroid cancer (MTC) and are also frequently seen in patients with papillary thyroid cancer and non–small cell lung cancer (NSCLC). However, no drugs that specifically target RET are currently approved by the U.S. Food and Drug Administration.
“There is a critical unmet need for effective drugs against cancers that have the RET alteration,” said Vivek Subbiah, M.D., an assistant professor in the Department of Investigational Cancer Therapeutics at The University of Texas MD Anderson Cancer Center.
Dr. Subbiah is MD Anderson’s principal investigator of a multi-institutional clinical trial (No. 2016-1007) of BLU-667. The dose-escalation trial is currently enrolling patients who have any type of solid tumor with a RET alteration and patients who have MTC regardless of RET status. All patients must have unresectable tumors and advanced disease; patients with a targetable mutation in EGFR, ALK, or ROS1 are excluded from the trial.
Dr. Subbiah said that the trial’s early results are promising. Among 40 evaluable patients, all with RET-altered cancers, the objective (complete and partial) response rate was 45%. The overall response rates were 40% and 50% among patients with MTC and NSCLC, respectively. As of April 6, 2018, 41 of 51 enrolled patients continue to receive BLU-667.
Most adverse events were grade 1, including constipation, elevated aspartate or alanine aminotransferase levels, diarrhea, and fatigue. However, three patients experienced grade 3 adverse events: elevated alanine aminotransferase, hypertension, and tumor lysis syndrome. Tumor reductions were seen in 83% of evaluable patients treated with doses of at least 60 mg/day.
In April 2018, Dr. Subbiah, Mimi Hu, M.D., an associate professor in the Department of Endocrine Neoplasia and Hormonal Disorders, and other colleagues published their preclinical and early clinical data on BLU-667 in Cancer Discovery (doi: 10.1158/2159-8290.CD-18-0338) and presented the trial’s early results at the American Association for Cancer Research Annual Meeting (presentation No. CT043).
OncoLog, May-June 2018, Volume 63, Issue 5-6