Loxo, Bayer biomarker-driven drug maintains high response rates in ESMO presentation

Larotrectinib showed an 81 percent response rate among 109 patients with NTRK fusion-positive cancers, with most continuing to respond or receiving surgery with curative intent after more than a year.

A drug under Food and Drug Administration review designed to target tumors based on rare genetic mutations regardless of age or where in the body they occur has continued showing high response rates, according to data presented Sunday.

US-based Loxo Oncology and Germany’s Bayer presented data on the drug, larotrectinib, at the European Society for Medical Oncology’s annual meeting in Munich. In 109 patients included in an efficacy analysis out of 122 total, the drug showed an overall response rate of 81 percent, including 80 percent among the primary dataset of 55 patients and 81 percent among a supplemental dataset of 67. The respective rates of complete responses – meaning patients whose tumors disappeared entirely – were 18 percent and 17 percent.

After 17.6 months of follow-up, the median duration of response was not reached — indicating that patients have not stopped responding to therapy – with 84 percent of all patients remaining on therapy or having undergone surgery with curative intent as of July. The patients were enrolled across three Phase I, Phase II and Phase I/II studies in adults and children.

The drug targets NTRK fusions, a kind of genetic anomaly seen in some cancers that drives tumor growth and whose inhibition via drug therapy has a strong likelihood of arresting that growth. The clinical trials enrolled patients aged one month to about 80 years with 24 different tumors exhibiting NTRK fusions, including 10 soft-tissue sarcomas, other sarcoma types, pancreatic cancer, melanoma, breast cancer, lung cancer and others. Though found across a broad range of tumor types, NTRK fusions’ occurrence varies considerably, from potentially all cases of infantile fibrosarcoma to 0.2-3 percent of lung cancers and 1 percent or less in colon cancer, sarcoma, glioblastoma and head and neck cancer, according to an information site run by Loxo and Bayer.

“In the supplementary set, the response rate is nearly the same as in the primary set, and duration of response has actually increased with longer patient follow-up,” said trial investigator Dr. Ulrik Lassen of the Rigshospitalet in Denmark, in a statement. “The larotrectinib experience provides strong clinical evidence supporting the development of single-purpose drugs against oncogenic driver targets and underscores the importance of tumor genomic profiling capable of identifying NTRK gene fusions alongside other activating alterations.”

The FDA gave the approval application for larotrectinib, also known as LOXO-101, priority review at the end of May and is expected to rule by Nov. 26. The companies filed for approval by the European Medicines Agency in August.

Another drug Loxo is testing is LOXO-292, which operates similarly to larotrectinib, but targets RET fusions. Data presented at the 2018 American Society of Clinical Oncology meeting in Chicago in June, showed a 74 percent confirmed response rate among 49 patients. The FDA gave Breakthrough Therapy Designation to LOXO-292 as a treatment for patients with RET fusion-positive cancers last week.

Targeting oncogenic driver mutations has become an important strategy in treatment of many cancers, aided in part by the growth of next-generation sequencing designed to detect them. Drugs targeting such mutations include Pfizer’s Xalkori (crizotinib), for ALK fusion-positive lung cancer, and Merck & Co.’s Keytruda (pembrolizumab), for microsatellite instability-high cancers regardless of the tissue affected.

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