ROCKLAND, Mass.—EMD Serono, the North American biopharmaceutical branch of Merck KGaA, Darmstadt, Germany, has announced that the FDA has approved Tepmetko (tepotinib), following Priority Review, for the treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) harboring mesenchymal-epithelial transition exon 14 (METex14) skipping alterations.
Tepmetko is an oral MET inhibitor that inhibits the oncogenic MET receptor signaling caused by MET gene alterations. Discovered and developed in-house at Merck KGaA, Tepmetko has a highly selective mechanism of action, with the potential to improve outcomes in aggressive tumors that harbor these specific alterations and have a poor prognosis. Tepmetko is the first and only FDA-approved MET inhibitor that offers once-daily oral dosing. The drug is administered as two 225 mg tablets (450 mg).
The approval is based on results from the pivotal Phase 2 VISION study, which is evaluating Tepmetko as a monotherapy in patients with advanced NSCLC with METex14 skipping alterations. Data from the primary analysis of the VISION study have been published online in The New England Journal of Medicine.
Tepmetko demonstrated an overall response rate of 43% (95% CI, 32–56) in treatment-naïve patients (n=69), and 43% (95% CI, 33-55) in previously treated patients (n=83). Median duration of response (DOR) was 10.8 months (95% CI, 6.9-NE) and 11.1 months (95% CI, 9.5-18.5) among treatment-naïve and previously treated patients, respectively. Duration of response of six months or more occurred among 67% of treatment-naïve patients and 75% of previously treated patients, and duration of response of nine months or more occurred among 30% of treatment-naïve patients and 50% of previously treated patients.
This indication has been approved under an accelerated approval pathway, based on overall response rate and duration of response. Continued approval for this indication may be contingent upon the verification and description of clinical benefit in confirmatory trials.
“METex14 skipping occurs in approximately 3% to 4% of NSCLC cases, and patients with this aggressive lung cancer are often elderly and face a poor clinical prognosis. There is a pressing need for targeted treatments that have the potential to generate durable anti-tumor activity and improve the lives of patients with this challenging disease,” said Dr. Paul K. Paik, clinical director of the Thoracic Oncology Service at Memorial Sloan Kettering Cancer Center, and primary investigator in the VISION trial. “Tepmetko offers an important and welcome new therapeutic option for patients with metastatic NSCLC harboring these genetic mutations.”
“In recent years, the treatment of lung cancer has seen powerful progress in the understanding of the genetic mutations that lead to tumor growth, resistance and progression,” noted Andrea Ferris, president and CEO of LUNGevity. “The availability of a new precision medicine for NSCLC with METex14 skipping alterations advances patient access to targeted treatment and underscores the importance of routine comprehensive biomarker testing for patients with this challenging cancer.”
Tepmetko was the first oral MET inhibitor to receive a regulatory approval anywhere in the world for the treatment of advanced NSCLC harboring MET gene alterations, with its approval in Japan in March 2020. The FDA completed its review of Tepmetko under its Real-Time Oncology Review pilot program, after previously granting the medicine Breakthrough Therapy Designation. The FDA has also recently granted Tepmetko Orphan Drug Designation.
A Marketing Authorization Application for Tepmetko for a similar indication was validated by the European Medicines Agency in November 2020. Applications have also been submitted in Australia, Switzerland, and Canada under the FDA’s Project Orbis initiative, which provides a framework for concurrent submission and review of oncology medicines among international partners.
“This approval of Tepmetko by the FDA is an important milestone on our mission to significantly improve the treatment of cancer where MET plays a driving role. Our focus now is to ensure Tepmetko is accessible to patients in the United States and fully integrated into clinical practice, given the important advance it represents for indicated patients as an oral once-a-day precision medicine,” stated Dr. Danny Bar-Zohar, global head of Development for the Healthcare business of Merck KGaA.
Tepmetko is also being investigated in the Phase 2 INSIGHT 2 study in combination with osimertinib in MET amplified, advanced, or metastatic NSCLC harboring activating EGFR mutations that has progressed following first-line treatment with osimertinib. Additionally, Tepmetko is being studied in the Phase 2 PERSPECTIVE study in combination with cetuximab in patients with RAS/BRAF wild-type left-sided metastatic colorectal cancer, who have acquired resistance to anti-EGFR antibody targeting therapy due to MET amplification.