ASCO 2020: Targeted Treatment Shows Promise in Non-Small Cell Lung Cancer

Paul K. Paik, MD, Clinical Director, Thoracic Oncology Service

Paul K. Paik, MD, Clinical Director, Thoracic Oncology Service

Researchers at Memorial Sloan Kettering Cancer Center (MSK) published updated data today in the New England Journal of Medicine from the ongoing, single-arm phase II VISION study evaluating tepotinib as a single agent in patients with advanced non-small cell lung cancer (NSCLC) with MET exon 14 (METex14) skipping alterations. This data is also featured as part of the American Society of Clinical Oncology’s (ASCO) 2020 Virtual Scientific Program. Researchers reported that tepotinib showed robust and durable clinical response, manageable toxicity and METex14 ctDNA depletion in patients with METex14 skipping NSCLC.

“These findings validate METex14 skipping as a bona fide therapeutic target, underscore the importance of routine testing for METex14 skipping in the clinic by liquid or tissue biopsy, and show that tepotinib is a precision therapy for patients with METex14 skipping,” said Paul K. Paik, MD, Clinical Director, Thoracic Oncology Service, MSK, principle investigator and lead author. “While outcomes with available therapies are typically poor in this patient population, this promising data allows us to harness the power of precision oncology and provide a targeted treatment option to these individuals.”

Tepotinib is a once-daily, orally available, potent and highly selective MET tyrosine kinase inhibitor that has shown promising clinical activity in patients with MET-driven tumors. Alterations of the MET signaling pathway are found in various cancer types, including 3 to 5 percent of NSCLC cases, and correlate with aggressive tumor behavior and poor clinical prognosis. Patients with NSCLC harboring METex14 skipping tend to be older than those with NSCLC harboring other alterations.

This phase II study of tepotinib enrolled patients with advanced/metastatic NSCLC with METex14 skipping. The primary endpoint was confirmed objective response rate (ORR) by independent review after ≥9 months’ follow-up, analyzed independently, in three populations according to the method of detecting METex14 skipping: liquid and/or tissue biopsy (combined group), liquid-biopsy group, and tissue-biopsy group.

As of January 2020, of 6,708 patients prescreened, 152 patients received tepotinib (safety population) and 99 patients comprised the primary efficacy population (combined group). ORR by independent review was 46.5 percent for the combined group, with a median duration of response of 11.1 months. ORR was 48.5 percent for the liquid-biopsy group (n=66) and 50.0 percent for the tissue biopsy group (n=60). Investigator-assessed ORR was 55.6 percent. ORR was consistent across treatment-naïve and previously treated patients. A molecular ctDNA response (METex14 depletion) was observed in 34/51 patients with serial on-treatment liquid biopsies; 23/34 had objective response and 7 stable disease. The VISION study met its primary endpoint and showed that the selective MET inhibitor tepotinib has durable clinical activity in patients with lung cancer with METex14 skipping. Results from this study led to regulatory approval of tepotinib in March 2020 in Japan.

“Tepotinib In Patients With MET Exon 14 Skipping Non-Small Cell Lung Cancer” was published in the New England Journal of Medicine on May 29, 2020. Dr. Paik served as lead author. Dr. Paik has provided compensated advisory services to EMD Serono/Merck.