Loxo Cancer Drug Targets Gene Mutation With Durable Responses in Early Study


“Precision medicine applied to cancer works like this: A sample of a patient’s tumor is analyzed on a molecular level, looking for genetic mutations in the cells known to cause cancer. Once identified, doctors can use drugs that target these specific genetic mutations to treat and hopefully kill the cancer cells.

“Cancers and the drugs that treat them are still identified largely by the affected organ — lung, breast, prostate, colon. If precision medicine takes hold in the future, cancer drugs will be developed and approved based on the genetic mutation they target, not the body part.

“Loxo Oncology (LOXO) and Ignyta (RXDX) are presenting new data at a medical meeting Sunday on drugs designed to target a mutation known as TRK gene fusions found in a cluster of different anatomically identified cancers.”

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New NTRK-targeted Therapy Shows Early Promise Against Tumors With NTRK Gene Fusions

“The investigational anticancer therapeutic LOXO-101, which targets a family of proteins called neurotrophic tyrosine kinase receptors (NTRKs), was safe, tolerable, and showed signs of clinical activity in patients who had tumors with a specific type of NTRK genetic alteration called a gene fusion, according to data from a phase I clinical trial presented at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics, held Nov. 5–9.

“ ‘Prior studies have shown that NTRK gene fusions drive the growth of tumors in preclinical models and are found in a wide array of tumor types,’ said 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. ‘These preliminary results from the first-in-human clinical trial of the NTRK-targeted investigational agent LOXO-101 help to validate NTRK gene fusions as drivers of several cancer types and suggest that LOXO-101 is a safe, tolerable, and potentially effective option for these patients.’ “

Prevalence of New Genetic Driver in Lung Cancer Shown in Study

“A line has been drawn from mutation of the gene NTRK1, to its role as an oncogene in non-small cell lung cancer, to treatment that targets this mutation. ‘Everything we know about lung cancer points to the idea that when we find one of these genetic drivers and can target it with a drug, patients will respond and tend to have a good amount of time on drug before it becomes ineffective. Obviously we can’t guarantee the effectiveness of targeting the NTRK1 mutation at this point, but everything we know about these kinds of genes makes us extremely hopeful,’ says one researcher.”

Editor’s note: A new targeted therapy treatment may be on the horizon for some lung cancer patients. Targeted therapies work by targeting specific molecules inside cancer cells. Often, these molecules are proteins that are mutated and cause cancer cells to multiply rapidly, contributing to tumor growth. There are several mutated proteins commonly found in non-small cell lung cancer (NSCLC) tumors. For a given patient, these can be detected by molecular testing, and based on the results, doctors can prescribe certain targeted therapy drugs. A newly discovered mutation called NTRK1 is being explored as a potential target for a new targeted therapy. To test the new drug, called LOXO-101, scientists have started a new clinical trial and are enrolling patients whose tumors have NTRK1 mutations.