Results of potentially registrational VISION study of tepotinib to treat NSCLC MET exon 14 skipping mutations.

Merck KGaA, a leading science and technology company, presented updated results from the potentially registrational Phase II VISION study , showing durable anti-tumor clinical activity for the investigational targeted therapy tepotinib across different lines of treatment in advanced non-small cell lung cancer (NSCLC) patients harboring MET exon 14 skipping mutations detected by liquid biopsy (LBx) or tissue biopsy (TBx). Data were shared in an oral presentation at the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago,

"Tepotinib has been designed to potentially improve outcomes in aggressive tumors that have a poor prognosis and harbor these specific alterations,” said Luciano Rossetti, Global Head of Research & Development for the Biopharma business of Merck. “Tepotinib is an important part of our strategic focus on precision medicine, and both the proportion of patients responding and the duration of anti-tumor clinical activity demonstrate the potential of this investigational therapy.”

Discovered in-house at Merck, tepotinib is an investigational, highly potent and selective1 oral MET kinase inhibitor that is designed to inhibit the oncogenic signaling caused by MET (gene) alterations, including both MET exon 14 skipping mutations and MET amplifications, or MET protein overexpression. Alterations of the MET signaling pathway are found in various cancer types, including 3-5% of NSCLC cases, and correlate with aggressive tumor behavior and poor clinical prognosis. Results from the ongoing Phase II VISION study in 73 efficacy-evaluable patients with NSCLC with MET exon 14 skipping mutations identified by LBx or TBx demonstrate overall objective response rate (ORR) of 50.0% for LBx-identified patients as assessed by Independent Review Committee (IRC), and 55.3% as assessed by investigators. The ORR for TBx-identified patients was 45.1% and 54.9%, respectively. The overall median duration of response (DOR) was 12.4 months and 17.1 months among LBx-identified patients, as assessed by IRC and investigators, respectively, while among TBx-identified patients, 15.7 and 14.3 months were observed, respectively.

Most treatment-related adverse events (TRAEs) were Grade 1 and 2. No Grade 4 or 5 TRAEs were observed. Any grade treatment-related adverse events (TRAEs) reported by greater than 10% of 87 patients evaluable for safety were peripheral edema (48.3%), nausea (23.0%) diarrhea (20.7%) and increased blood creatinine (12.6%). Other relevant TRAEs of any grade include increased lipase (4.6%), fatigue (3.4%) and vomiting (3.4%). TRAEs led to permanent discontinuation in four patients (two patients due to peripheral edema, one due to interstitial lung disease, one due to diarrhea and nausea).The use of both liquid and tissue biopsies to identify patients for the VISION trial is intended to support improved patient selection and is consistent with the company’s focus on patient-centric drug development.

Tepotinib is currently being investigated in NSCLC in two different settings: in NSCLC harboring MET alterations (MET exon 14 skipping mutations and MET amplifications) as monotherapy, as well as in combination with the tyrosine kinase inhibitor (TKI) osimertinib in epidermal growth factor receptor (EGFR) mutated MET amplified NSCLC having acquired resistance to prior EGFR TKI. Additional information on these clinical trials can be found at ClinicalTrials.gov using the identifiers NCT02864992 and NCT03940703, respectively. Merck is also actively assessing the potential of investigating tepotinib in combination with novel therapies for other tumor indications.