NEW ORLEANS —The investigational drug LOXO-101, which selectively targets a family of proteins called neurotrophic tyrosine kinase receptors (NTRKs), produced significant tumor regression in patients whose tumors had the NTRK gene fusions, according to data from a phase I clinical trial presented here at the AACR Annual Meeting 2016, April 16-20.
The study, led by David S. Hong, MD, deputy chair and associate professor in the Department of Investigational Cancer Therapeutics at The University of Texas MD Anderson Cancer Center in Houston, provides an update to data that was presented at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics in November 2015.
Hong said that at that time, of the 30 patients enrolled in the study, six had tumors with NTRK gene fusions, which have been shown to drive tumor growth. At that time, only three patients had been on the study long enough for a response assessment, and all three demonstrated partial responses. The other three patients had only recently enrolled.
Since then, Hong said, “We’ve now seen efficacy with significant tumor regression in all six patients whose tumors had NTRK-fusion.” A seventh patient with an NTRK fusion in the tumor has recently joined the study, and is not yet eligible for a response assessment, he said.
Hong added these seven patients have five different tumor types: sarcoma, papillary thyroid cancer, mammary analog secretory carcinoma of the salivary glands, non-small cell lung cancer, and GI stromal tumor.
Five of the six patients had confirmed partial responses according to RECIST 1.1 criteria, while the sixth patient had an 18 percent tumor regression. All seven patients remain on study with no evidence of progressive disease. The first patient has been on study for more than one year and all six efficacy-evaluable patients are at least into the seventh cycle of treatment. The clinical trial was not limited to patients with NTRK fusion-positive tumors, and the patients with tumors negative for the NTRK fusion have shown no objective antitumor activity, Hong said. The investigators have enrolled 43 patients as of March 2016.
Hong said LOXO-101 has been well tolerated. Researchers used a dose-escalation trial design, with patients receiving 50 milligrams (mg), 100 mg, or 200 mg once per day, or 100 mg or 150 mg twice a day. The maximum tolerated dose has not been reached, and the most common adverse events are grade 1 and 2 fatigue, constipation, and dizziness.
Hong said a limitation of the study is its small size. A phase II basket study of LOXO-101 is underway, and will test the drug in more patients with a wider variety of tumors, with a set dosage of 100 mg twice a day, given that this dose was well-tolerated and could induce durable disease-control in patients with NTRK gene fusions. The phase II trial will enroll only patients who have tested positive for NTRK fusions.
“The phase II study is important not only for generating additional data on LOXO-101 in patients with NTRK-fusion cancers, but we anticipate it will further broaden the range of tumor types that we’ve tested thus far. If the efficacy data continue to look promising, this trial may be able to support registering the drug with the FDA [U.S. Food and Drug Administration] and regulatory authorities around the world,” Hong said.
This study was funded by Loxo Oncology. Hong has conducted research for Loxo Oncology and Ignyta Research.