Intracranial Activity of Tepotinib in Patients with MET Exon 14 (METex14) Skipping Non–Small-Cell Lung Cancer (NSCLC) Enrolled in VISION

November 2022 Vol 13, No 11 —November 17, 2022

Rebecca Hill,1 Natasha Leighl,2 Christine Bestvina,3 Jyoti Patel,4 Xiuning Le,5 Remi Veillon,6 Ian Anderson,7 Ingel Demedts,8 Marina Chiara Garassino,9 Julien Mazières,10 Masahiro Morise,11 Egbert Smit,12 S. Peter Eggleton,13 Aurora O’Brate,14 Rolf Bruns,15 Svenja Adrian,16 Paul K. Paik17

1Medical Science Liaison, Oncology at EMD Serono, Nashville, TN, USA; 2Department of Medical Oncology, Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, Ontario, Canada; 3University of Chicago Medical Center, Chicago, IL, USA; 4Lurie Cancer Center, Northwestern University-Feinberg School of Medicine, Chicago, IL, USA; 5Department of Thoracic Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; 6CHU Bordeaux, Service des Maladies Respiratoires, Bordeaux, France; 7St Joseph Heritage Healthcare, Anaheim, CA, USA; 8Department of Pulmonary Diseases, AZ Delta Hospital, Roeselare, Belgium; 9Department of Medicine, Section of Hematology/Oncology, Knapp Center for Biomedical Discovery, The University of Chicago, IL, USA; 10CHU de Toulouse, Université Paul Sabatier, Toulouse, France; 11Department of Respiratory Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan; 12Department of Pulmonary Diseases, Leiden University Medical Centre, Leiden, The Netherlands; 13Global Clinical Development, Merck Serono Ltd., Feltham, UK, an affiliate of Merck KGaA, Darmstadt, Germany; 14Global Medical Affairs, the healthcare business of Merck KGaA, Darmstadt, Germany; 15Department of Biostatistics, the healthcare business of Merck KGaA, Darmstadt, Germany; 16Global Clinical Development, the healthcare business of Merck KGaA, Darmstadt, Germany; 17Department of Medicine, Thoracic Oncology Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Department of Medicine, Weill Cornell Medical College, New York, NY, USA

Background: Brain metastases (BMs) occur in 20% to 40% of patients with METex14 skipping NSCLC.1–4 As part of the multidisciplinary teams that manage cancer patients, oncology nurse navigators play a key role in optimal patient management strategy. In the phase 2 VISION study, tepotinib, a once-daily and highly selective MET tyrosine kinase inhibitor, demonstrated an objective response rate (ORR) of 50.8% and a median duration of response (mDOR) of 18.0 months in patients with METex14 skipping NSCLC (NCT02864992; Cohorts A+C, N = 313).5

Objective: To provide analysis of the intracranial activity of tepotinib in patients with METex14 skipping NSCLC with BM from the VISION study to aid oncology nurse navigators who manage this population of patients.

Methods: Patients with METex14 skipping NSCLC received oral tepotinib 500 mg once daily (450 mg active moiety). Patients with BM (asymptomatic and symptomatic/stable) were eligible. The primary end point was systemic ORR by an independent review committee (RECIST v1.1, accounting for both intra- and extracranial lesions); a subgroup analysis in patients with BM was predefined (data cutoff: February 20, 2022).

An exploratory analysis of brain lesions was conducted by an independent review using RANO-BM criteria. Responses were determined in patients with ≥1 evaluable postbaseline tumor assessment. For those with only nontarget lesions (NTLs) per RANO-BM (enhancing and nonenhancing NTLs), disease control was defined as at least noncomplete response/nonprogressive disease.

Results: Fifty-seven patients had baseline BM (Cohorts A+C, n = 313). Systemic ORR was 56.1% (95% CI, 42.4-69.3), and mDOR was 9.0 months (95% CI, 5.6-not estimable [ne]).

Forty-three patients were evaluable by RANO-BM, 30 (69.8%) of whom received prior brain radiotherapy or surgery. Twenty-three patients were treatment-naive, and 20 patients had received prior therapy lines. Overall intracranial disease control rate was 88.4% (95% CI, 74.9-96.1) with an intracranial progression-free survival of 20.9 months (95% CI, 5.7-ne).

Fifteen patients had target BM lesions. Intracranial best objective responses were complete responses in 3 patients and partial responses in 7 patients; 3 patients had stable disease and 2 had progressive disease. Overall, intracranial ORR in patients with target lesions was 66.7% (95% CI, 38.4-88.2) with an intracranial DOR of ne (95% CI, 0.9-ne).

Conclusions: In summary, the MET tyrosine kinase inhibitor tepotinib showed robust systemic activity in patients with METex14 skipping NSCLC with BM. In addition, tepotinib demonstrated promising intracranial activity in an exploratory analysis conducted using RANO-BM criteria. These results will not only inform practitioners in clinical decision-making but also oncology nurse navigators responsible for optimizing the treatment experience of patients with METex14 skipping NSCLC with BM.

Industry sponsor: The healthcare business of Merck KGaA, Darmstadt, Germany.

Clinical trial identifier: NCT02864992.


  1. Mazieres J, et al. European Lung Cancer Virtual Congress 2021. ePoster159P.
  2. Offin M, Jia Luo, Guo R, et al. CNS metastases in patients with MET Exon 14-altered lung cancers and outcomes with crizotinib. JCO Precis Oncol. 2020;4:PO.20.00098.
  3. Digumarthy SR, Mendoza DP, Zhang EW, et al. Clinicopathologic and imaging features of non-small-cell lung cancer with MET Exon 14 skipping mutations. Cancers (Basel). 2019;11:2033.
  4. Awad MM, Leonardi GC, Kravets S, et al. Impact of MET inhibitors on survival among patients with non-small cell lung cancer harboring MET exon 14 mutations: a retrospective analysis. Lung Cancer. 2019;133:96-102.
  5. Thomas M, Garassino M, Felip E, et al. Tepotinib in patients with MET Exon 14 (METex14) skipping NSCLC: primary analysis of the confirmatory VISION cohort C. World Conference on Lung Cancer 2022. Oral OA03.05.
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