Targetable Mutations in NSCLC: More Testing Needed!


Diagnosis of adenocarcinoma of the lung, a major subtype of non-small lung cancer (NSCLC), nowadays triggers mandatory testing of tumor tissue for alterations in four genes: EGFR, ALK, ROS1, and more recently, BRAF. If present, these alterations predict sensitivity to specific targeted drugs approved by the U.S. Food and Drug Administration (FDA) that work better and often longer than standard chemotherapy, and are better tolerated.

However, there are many more targetable/actionable genomic alterations (also known as “drivers”) in NSCLC. This blog post will briefly discuss most of them, with the goal of promoting molecular testing for more than the four “usual suspects” mentioned above. Some patients with these alterations may benefit from FDA-approved drugs or from enrollment in clinical trials that are testing additional drugs and drug combinations. Continue reading…


Ignyta Announces Updated Data from Entrectinib Phase 1 Clinical Trials at the 2016 AACR Annual Meeting

Excerpt:

“Ignyta, Inc. (RXDX),a precision oncology biotechnology company, today announced that updated results of its Phase 1 clinical trials of entrectinib, the company’s proprietary oral tyrosine kinase inhibitor targeting solid tumors harboring activating alterations to NTRK1, NTRK2, NTRK3, ROS1 or ALK, were presented in an oral plenary session at the 2016 Annual Meeting of the American Association for Cancer Research (AACR) in New Orleans, Louisiana.

“ ‘We continue to be excited by entrectinib’s ability to help patients with advanced cancer,’ said Jonathan Lim, M.D., Chairman and CEO of Ignyta. ‘With respect to efficacy, in the 25 patients in the Phase 1 trials who would meet the eligibility criteria for our Phase 2 clinical trial, we saw tumor regression in 20 patients, or 80%. Nineteen out of 24 patients with extracranial solid tumors had a confirmed RECIST response, representing a 79% overall response rate; and one patient with an astrocytoma had evidence of substantial tumor regression by volumetric measurement. These responses were observed in patients with each of NTRK, ROS1 and ALK rearrangements, and across six tumor histologies, including complete and/or durable responses in both primary and metastatic tumors of the central nervous system.’ ”

Go to full article.

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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.’ “