Join PER® September 15th for the New York Advanced Practice Collaborative Meeting! Directed toward NP/PAs, this meeting blends presentations on cutting-edge information with panel discussions to enhance learning.

Lung Cancer Trial Takes Aim at MET Mutation

ANITA SHAFFER | February 14, 2017
Paul K. Paik, MD

Paul K. Paik, MD

Tepotinib (MSC2156119J), an investigational small molecule that targets a recently identified aberration in the MET gene, is moving forward rapidly in clinical development for patients with non-small cell lung cancer (NSCLC) who harbor the mutation, raising hopes that a more specific attack on the signaling pathway will lead to a new therapy for a significant subgroup of individuals with the disease.
An estimated 3% to 4% of patients with NSCLC are believed to harbor the skipping mutation, about the same frequency as the incidence of ALK rearrangements, said Paul K. Paik, MD, a medical oncologist at Memorial Sloan Kettering Cancer Center who is the global principal investigator on the trial.
“It’s an unmet need for those patients, which translates worldwide to quite a large number of people,” considering the prevalence of lung cancer, he said.
To target MET, investigators have tried 2 strategies: monoclonal antibodies directed against the MET receptor or its ligand and tyrosine kinase inhibitors. However, results have been mixed. In addition, there are 2 multikinase inhibitors approved by the FDA, crizotinib (Xalkori) and cabozantinib (Cometriq/Cabometyx), which among other receptors also target MET. Now, the focus has shifted to the exon 14 skipping mutation as an alteration that appears predictive for response to MET inhibitors, Paik said.
Paik said tepotinib inhibits MET more potently than crizotinib and, because of its specificity, appears to have fewer adverse effects. The appropriate dosing was established in phase I testing. Patients treated with the drug have experienced fewer of the adverse events typical of the MET-targeting class of drugs, such as gastrointestinal side effects, liver function laboratory abnormalities, and peripheral edema, according to Paik. “In terms of tolerability in the phase I experience, it’s a very well-tolerated drug,” he said.
This single-arm, phase II trial aims to enroll 60 patients who will be treated with a 500-mg, once-daily tepotinib tablet during each 21-day cycle until disease progression. The study’s primary endpoint is objective response by independent review; secondary endpoints include duration of response, disease control, and progression-free survival.
The trial is open to patients with stage IIIB/IV lung adenocarcinomas who have progressed after prior chemotherapy and whose tumors test positive for the MET exon 14 skipping mutation.
Tepotinib also is being evaluated in a more broadly MET-positive population in a phase I/II trial (NCT0198255). In that study, patients with locally advanced or metastatic NSCLC are being randomized to receive either tepotinib plus gefitinib or platinum plus pemetrexed. The agent is being developed by Merck KGaA, Darmstadt, Germany, and operates in the United States as EMD Serono, Inc.

Talk about this article with nurses and others in the oncology community in the General Discussions Oncology Nursing News discussion group.
External Resources

MJH Associates
American Journal of Managed Care
MD Magazine
Pharmacy Times
Physicians' Education Resource
Specialty Pharmacy Times
OncNurse Resources

Continuing Education
Web Exclusives

About Us
Advisory Board
Contact Us
Privacy Policy
Terms & Conditions
Intellisphere, LLC
2 Clarke Drive
Suite 100
Cranbury, NJ 08512
P: 609-716-7777
F: 609-716-4747

Copyright OncNursing 2006-2018
Intellisphere, LLC. All Rights Reserved.